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IMPAACT 2002: Cognitive Behavioral Therapy and Medication Management for Treatment of Depression in US Youth With HIV

Primary Purpose

HIV, Depression

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Health and Wellness Combined Cognitive Behavioral Therapy and a Medication Management Algorithm

Enhanced Standard of Care

About this trial

This is an interventional treatment trial for HIV focused on measuring Cognitive Behavioral Therapy, Medication Management

Eligibility Criteria

12 Years - 24 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Receiving mental health or HIV-related care at participating US IMPAACT site
Confirmed HIV-1 Infection
Aware of his or her HIV infection
Per clinician assessment, primary diagnosis of nonpsychotic depression, including Major Depressive Disorder, Depression Not Otherwise Specified (NOS), or Dysthymia, as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV or DSM-V criteria
Current depressive symptoms that warrant intervention as determined by a score of ≥ 11 on the Quick Inventory of Depressive Symptomatology - Clinician (QIDS-C)
Able to communicate in spoken and written English
Able and willing to provide written informed assent/consent and able to obtain written parental or guardian permission (if required, as specified in site standard operating procedure (SOP), by State law, and/or Institutional Review Board (IRB) policy) to be screened for and to enroll in IMPAACT 2002

Exclusion Criteria:

Known or self-reported history of any psychotic disorder and/or bipolar I or II disorder
Severe disorders (more than 6 symptoms) based on DSM-V criteria related to alcohol, cannabis or other substances; or those with moderate symptoms (4 or 5 symptoms) who are also currently experiencing withdrawal or dependence symptoms; within the past month prior to enrollment
Per clinician assessment at screening, depression and/or suicidal ideation requiring more intensive treatment than the study provides or at immediate risk of being a danger to themselves or others
Per participant report at screening, intends to relocate away from the study site during study participation
Currently in therapy with a non-study provider, unless willing to switch to a study-trained provider
Has any other condition that, in the opinion of the Investigator of Record (IoR)/designee, would preclude informed assent/consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

COMB-R

Enhanced Standard of Care

Arm Description

Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention

Enhanced Standard of Care (ESC)

Outcomes

Primary Outcome Measures

Depression Outcomes: Quick Inventory of Depression Symptomatology - Self Report (QIDS-SR) Score

The QIDS-SR ranges from 0-27 and assesses the severity and number of depression symptoms. Data completed through the Audio Computer Assisted Interview (ACASI) system are used for this outcome. A lower score indicates fewer depression symptoms and lower depression symptom severity. Scores for all participants at a site were averaged. The site-specific averages were then analyzed.

Depression Outcomes: Response to Treatment, Defined as a Decrease in QIDS-SR Score by >50%

We are assessing the percentage of participants with a response to treatment.The percentage of participants at each site with a response was calculated. These percentages were averaged for each treatment and the treatment averages were compared. A response to treatment is considered a decrease in Quick Inventory of Depression Symptomatology, Self Report (QIDS-SR) from Study entry to Week 24 by more than 50%. The week 0 value is generally considered the entry value. Priority is given to the ACASI score at week 0. In certain cases, the week 1 ACASI value is used if there is no ACASI score at week 0, but there is one at week 1. Paper form scores are used for "study entry" if there is no ACASI record, with the value at week 0 prioritized over the value at week 1. Otherwise, ACASI data are used for this outcome. The QIDS-SR is scored from 0 to 27 with a lower score indicating less symptomatology.

Depression Outcomes: Remission, Defined as a QIDS-SR Score <= 5

We computed the percentage of participants at each site with remission and then compared the percentages. Remission is defined as a Quick Inventory of Depression Symptomatology, self-report (QIDS-SR) score <= 5. ACASI data are used for this outcome. The QIDS-SR scale is from 0-27 with a lower score indicating tess symptomatology.

Biological Outcomes: Cluster of Differentiation 4 (CD4) Cell Count at Week 24

CD4 cell counts are cells/microL (uL). CD4 cell counts of all participants at a site were averaged. The averages were then analyzed.

Biological Outcomes: Plasma HIV RNA Level at Week 24

Plasma HIV RNA data are calculated on the log10 scale as log10(RNA copies/mL) For this analysis, HIV-1 RNA values (copies per mL) that were censored below the lower limit of quantification (LLQ) were imputed to be equal to the LLQ - 1. The LLQ was considered to be 40 copies/mL. Viral load was calculated on the log10 scale as log10(RNA copies/mL). Viral load suppression was also measured as copies < 40. The log10 (RNA copies/mL) values were averaged by site and those averages were analyzed.

Secondary Outcome Measures

Adherence Outcomes: Adherence to Anti-HIV Medications - Number of Days in Last 30 With Any Missed Doses

Adherence to anti-HIV medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report. The first of three questions was to assess the number of days in the last 30 with any missed medication doses.The average number of days for all participants at a site were averaged. The site-specific averages were then analyzed.

Adherence Outcomes: Adherence to Anti-HIV Medications - How Good Participant Was at Taking Medicines as Instructed

Adherence to anti-HIV medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report. The second of three questions was how good the participant is at taking his medication as instructed in the last 30 days. Response scales are Likert from 1 to 6, with a higher score indicating better adherence. 1=Very poor .... 6=Excellent. The average score for all participants at each site was computed and these site-level summaries were compared across treatments.

Adherence Outcomes: Adherence to Anti-HIV Medications - How Often Did Participant Take Medications as Instructed

Adherence to anti-HIV medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report. The third of three questions was how often the participant took medication correctly in the last 30 days. Response scales are Likert from 1 to 6, with a higher score indicating better adherence. 1=Never ... 6=Always. The average score for all participants at a site was computed and these site-level summaries were compared across treatments.

Adherence Outcomes: Adherence to Psychiatric Medications - Number of Days in Last 30 With Any Missed Doses

Adherence to depression medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report for those participants taking depression medications. Three questions were asked; The first of the three questions was to assess the number of days in the last 30 with any missed medication doses.The average number of days for all participants at a site were averaged. The site-specific averages were then analyzed.

Adherence Outcomes: Adherence to Psychiatric Medications - How Good Participant Was at Taking Medications as Instructed

Adherence to depression medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report tor those participants taking depression medications. The second of three questions was how good the participant is at taking his medication as instructed during the last 30 days. Response scales are Likert from 1 to 6, with a higher score indicating better adherence.1=Very poor .... 6=Excellent. The average score for all participants at each site was computed and these site-level summaries were compared across treatments.

Adherence Outcomes: Adherence to Psychiatric Medications - How Often Did Participant Take Medicines as Instructed

Adherence to depression medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report for those participants taking depression medications. The third of three questions was how often the participant took medication correctly in the past 30 days. Response scales are Likert from 1 to 6, with a higher score indicating better adherence: 1=Never .... 6=Always. The average score for all participants at each site was computed and these site-level summaries were compared across treatments.

Adherence Outcomes: Adherence to Psychotherapy Sessions

We computed the number of scheduled counseling sessions attended. The average number of sessions was computed for all participants at each site and these site-level averages were compared across treatments.Where study visits for weeks 0 and 1 were held on the same day, the counseling session for week 1 would have been administered at week 0.

Adherence Outcomes: Adherence to COMB-R Medication Management Sessions

We computed the number of scheduled medication management sessions (COMB-R only) attended. The average number of sessions was computed for all participants at each site. We took the mean of the site-level averages.

Adherence Outcomes: Adherence to Study Visits

We computed the number study visits completed as the number of scheduled study visits completed to date as of week 24 and week 48. However in some cases, weeks 0 and 1 visits were done on the same day. In that case, they were counted as separate visits.The average number of visits was computed for all participants at each site and these site-level averages were compared across treatments.

Depression Outcomes: Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) Score Over 48 Weeks.

The Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) score ranges from 0-27 and assesses the severity and number of depression symptoms. Data completed through the Audio Computer Assisted Interview (ACASI) system were used for this outcome. A lower score indicates fewer depression symptoms and lower depression symptom severity. Scores for all participants at a site were averaged. The site-specific averages were then analyzed.

Depression Outcomes: Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) Response to Treatment Over 48 Weeks, Defined as a Decrease in QIDS-SR Score by > 50%

A response to treatment was considered to be a decrease in Quick Inventory of Depression Symptomatology, Self Report (QIDS-SR) from Study entry to Week 48 by more than 50%. The week 0 value was generally considered the entry value. Priority was given to the ACASI score at week 0. In certain cases, the week 1 ACASI value was used if there was no ACASI score at week 0, but there was one at week 1. Paper form scores were used for "study entry" if there were no ACASI records, with the value at week 0 prioritized over the value at week 1. Otherwise, ACASI data were used for this outcome. The QIDS-SR was scored from 0 to 27 with a lower score indicating less symptomatology.The percentage of participants with a QIDS-SR response at each site was calculated. These percentages were averaged for each treatment and the treatment averages were compared.

Depression Outcomes: Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) Score Remission Over 48 Weeks

Remission is defined as a Quick Inventory of Depression Symptomatology, self-report (QIDS-SR) score of 5 or less. ACASI data are used for this outcome. The QIDS-SR scale is from 0-27 with a lower score indicating tower depression symptomatology. We computed the percentage of participants at each site with remission and then compared the site-level percentages across treatments.

Effect of Demographic, Behavioral, and Biological Modifiers on Depression Outcomes: Quick Inventory of Depression Symptomatology (QIDS-SR) Score

QIDS-SR score (defined in Outcome 15). Effect of moderators on depression outcomes:Demographic: age group, gender, mode of HIV acquisition, initial level of depression (QIDS-SR categorized as severe/very severe vs. moderate or less severity); Biological: baseline CD4 (count/uL categorized as stage 3 [< 200 cells] vs. less than stage 3), nadir CD4 at study entry (based on count/uL and considering worst classification across ages, defined below), plasma HIV RNA suppression status, Center for Disease Control and Prevention (CDC) clinical stage at entry (Stage 3 vs. less than stage 3): Determination of nadir CD4 cell count as Stage 3 was based on the following: If any of the following were true, the overall CD4 nadir cell count was classified as Stage 3: <750 cells at < 1 year of age; < 500 cells at 1-5 years of age; <200 cells at 6+ years of age (from Revised Surveillance Case Definition for HIV Infection - United States, 2014). See analysis section for description of method.

Effect of Demographic, Behavioral, and Biological Modifiers on Depression Outcomes: Response to Treatment

Response to Treatment (defined in Outcome 16): Effect of moderators on depression outcomes: Demographic: age group, gender, mode of HIV acquisition, initial level of depression (QIDS-SR categorized as severe/very severe vs. moderate or less severity); Biological: baseline CD4 (count/uL categorized as stage 3 [< 200 cells] vs. less than stage 3), nadir CD4 at study entry (based on count/uL and considering worst classification across ages, defined below), plasma HIV RNA suppression status, Center for Disease Control and Prevention (CDC) clinical stage at entry (Stage 3 vs. less than stage 3): Determination of nadir CD4 cell count as Stage 3 was based on the following: If any of the following were true, the overall CD4 nadir cell count was classified as Stage 3: <750 cells at < 1 year of age; < 500 cells at 1-5 years of age; <200 cells at 6+ years of age (from Revised Surveillance Case Definition for HIV Infection - United States, 2014). See analysis section for description of method.

Effect of Demographic, Behavioral, and Biological Modifiers on Depression Outcomes: Remission

Remission (defined in Outcome 17): Effect of moderators on depression outcomes: Demographic: age group, gender, mode of HIV acquisition, initial level of depression (QIDS-SR categorized as severe/very severe vs. moderate or less severity); Biological: baseline CD4 (count/uL categorized as stage 3 [< 200 cells] vs. less than stage 3), nadir CD4 at study entry (based on count/uL and considering worst classification across ages, defined below), plasma HIV RNA suppression status, Center for Disease Control and Prevention (CDC) clinical stage at entry (Stage 3 vs. less than stage 3): Determination of nadir CD4 cell count as Stage 3 was based on the following: If any of the following were true, the overall CD4 nadir cell count was classified as Stage 3: <750 cells at < 1 year of age; < 500 cells at 1-5 years of age; <200 cells at 6+ years of age (from Revised Surveillance Case Definition for HIV Infection - United States, 2014). See analysis section for description of method.

Behavioral Risk Outcomes: Alcohol Use - Ever Used

The percent of participants who reported ever using alcohol was computed for each site. These site-level percentages were compared across treatment groups.

Behavioral Risk- Alcohol Use - Past 3 Months Regular Use Frequency

Frequency of alcohol use during the past three months was reported for those participants reporting at least some use ever; frequency was measured on a 5-point Likert scale from 1 to 5 (1=Never, 2=Once or twice, 3 = monthly, 4=weekly, 5 = daily or almost daily). A lower score indicates less alcohol use. The percentage of participants at each site with regular use (3=monthly, 4=weekly, 5=daily) was computed. The site-level percentages were compared across treatments.

Behavioral Risk - Alcohol Use - Number of Drinks Per Day

The number of alcoholic drinks per day on a typical day was reported. The average of the number of drinks for all participants at each site was computed and these site-level averages were compared across treatments. Analysis was limited to those participants reporting at least some use ever.

Behavioral Risk - Alcohol Use - Binge Drinking

Binge drinking is defined by the number of days with 5 or more drinks in a row (within a couple of hours) during the past 3 months. These numbers were averaged for all participants at each site and the site-level averages were compared across treatments.Analysis was limited to those participants reporting at least some use ever.

Behavioral Risk Outcomes: Tobacco Use- Ever Used

The percent of participants reporting tobacco use (ever) was computed for each site and these site-level averages were compared across treatments.

Behavioral Risk - Tobacco Use - Past 3 Months Regular Use Frequency

Past three months frequency of tobacco use was measured on a 5-point Likert scale (1=never, 2=once or twice, 3=monthly, 4 = weekly, 5=daily/almost daily). The percentage of participants with regular use (monthly, weekly or daily) was computed. Analysis was limited to those participants reporting at least some use ever.

Behavioral Risk Outcomes: Drug Use - Ever Used

For each of the following substances (cannabis, cocaine, amphetamine, inhalants, sedatives, hallucinogens, opioids) we computed the percent of participants at each site who reported ever using the substance. We also computed the site-level percentages of participants ever using any illegal substance excluding cannabis.

Behavioral Risk - Drug Use - Past 3 Months Regular Frequency of Use

Past three months use frequency for cannabis, cocaine, amphetamine, inhalants, sedatives, hallucinogens, opioids was assessed. This was measured on a 5-point Likert scale from 1=Never to 5=almost daily. A lower score indicates less frequent use. Scores were dichotomized as regular use (3=monthly, 4=weekly, 5=daily/almost daily) or low use (1=never, 2=once or twice). The percent of participants who used a substance at regularly, given they ever used it, was computed for each site. We also defined a variable of regular frequency of use for any illegal substance, excluding cannabis.

Behavioral Risk Outcomes: Sex-Risk Behaviors - Sex as Exchange Commodity

We considered a report of sex as exchange commodity if participant reported either that they gave sex in exchange for money, drugs or shelter or if they bought sex with money, drugs or shelter. This was only reported for participants who said they had had some sex (oral, vaginal or anal) ever. The percent of participants at each site who used sex as an exchange commodity was computed and the site-level percentages were compared across treatments.

Behavioral Risk Outcomes: Sex-Risk Behaviors - Importance of Using Condom

Participant reported importance that participant or partner use a condom on a scale from 0 to 100 with 0=not important at all, 50= about as important as the other things in my life and 100=most important thing in my life.This was only reported for participants who said they had had some sex (oral, vaginal or anal) ever. The average scores were computed for all participants at each site and the site-level averages were compared across treatments.

Behavioral Risk- Sex Risk Behaviors - Confidence in Condom Use

Participant reports how confident they are that she/he or partner will use condoms. Reported on a scale from 0-100 with 0=I do not think I will use condoms, 50=I have a 50% chance of using a condom; 100=I think I will definitely use a condom.This was only reported for participants who said they had had some sex (oral, vaginal or anal) ever. The average scores were computed for all participants at each site and the site-level averages were compared across treatments.

Behavioral Risk - Sex Risk Behaviors - Number of Sexual Partners in Past Three Months

The participant reported the number of sexual partners in the past three months. This was only reported for participants who said they had had some sex (oral, vaginal or anal) ever. The average number of sexual partners was computed for all participants at each site and the site-level summaries were compared across treatment groups.

Behavioral Risk - Sex Risk Behaviors. Low Use Frequency of Condom Use in Last Three Months - Main Partner

Main partner frequency of condom use was measured on a 5-point Likert scale from 1= always, 2 = more than half the time, 3= about half the time, 4=less than half the time to 5=never. It is only reported if participant reported some anal or vaginal sex in past three months. The worse (higher) score of that reported for vaginal or anal sex is analyzed. For each site we computed the percent of participants reporting low frequency of condom use (score = 3, 4 or 5). The site-level percentages were averaged and the site-level averages were compared across treatments.

Behavioral Risk - Sex Risk Behavior - Low Use Frequency of Condom Use in Past 3 Months - Other Partner

Condom use frequency for other than main partners was measured on a 5-point Likert scale from 1= always, 2 = more than half the time, 3= about half the time, 4=less than half the time to 5=never. It is only reported if participant reported some anal or vaginal sex in past three months. The worse (higher) score of that reported for vaginal or anal sex is analyzed. For each site we computed the percent of participants reporting low frequency of condom use (score = 3, 4 or 5). The site-level percentages were averaged and the site-level averages were compared across treatments.

To Describe the Implementation Fidelity at COMB-R Sites and the Counseling Strategies and Medication Patterns at ESC Sites: The Total Numbers of Counseling Sessions

We counted the total numbers of COMB-R and ESC counseling sessions administered over the intervention period (through week 24), including both interim and scheduled visits. The average number of sessions was computed for all participants at each site and those averages were compared across treatments.

Implementation Fidelity (COMB-R Sites) - Count of Participants Having Been Administered Various COMB-R Counseling Approaches

For COMB-R; we assessed numbers of participants for whom counselors reported using each type of cognitive behavioral therapy (CBT) approaches over the intervention period. A participant was counted in a specific category if the approach was ever used during the 24 week intervention period.

Counseling Strategies (ESC Sites) - Count of Participants Having Been Administered Various ESC Counseling Approaches

We summarized the types of counseling approaches used by the ESC clinicians over the intervention period. A participant was counted in a specific category if the approach was ever used during the 24 week intervention period.

Implementation Fidelity (COMB-R Sites); Medication Management - Number of Sessions

We computed the number of Medication Management (MM) sessions attended by participants in the COMB-R group over 24 weeks including both interim and scheduled visits .We averaged the number of sessions for all participants at each site and then took the mean of the site-level averages.

Implemental Fidelity (COMB-R) - Medication Management - Stages

We summarized the stages of the MM algorithm reported for participants by prescribing clinicians in the COMB-R group. Stage 0 is no medication. Stage 1 is monotherapy with a selective serotonin re-uptake inhibitor (SSRI). Stage 2 is monotherapy with a second SSRI. Stage 3 is monotherapy with a non-SSRI. Stage 4 is combination treatment with two antidepressants or an antidepressant plus lithium. Stages 1 through 3 also allow for partial responders to receive augmentation with selected other psychiatric medications.

Acceptability: Frequency of Psychiatric Medication Use - Percent of Participants on Psychiatric Medications

We assessed whether or not participants were taking psychiatric medications at week 24 and we computed the percent of participants at each site taking psychiatric medications overall and by classes of psychiatric medications. We compared the site-level percentages across treatment groups. Classes of medications included: any psychiatric medication, any antidepressant medication, any regimen with a selective serotonin re uptake inhibitor (SSRI), any regimen with a non-SSRI antidepressant medication, any other non-antidepressant psychiatric medication.

Acceptability - Frequency of Psychiatric Medication Use - Percent of Study Time on Psychiatric Medications Through Week 24

For those participants taking each of several classes of psychiatric medications during the first 24 study weeks, we computed the percent of study time during which each participant was taking psychiatric medications of that category. Regimen classes were: any psychiatric medication, any antidepressant medication, single selective serotonin re-uptake inhibitor (SSRI), single non-SSRI, SSRI+other medication, non-SSRI+other medication. Then the average percent of time on each category of medication was computed for all participants at each site. The site-level means were compared across treatments.

Acceptability: Number of Interim Visits - Counseling Sessions

We counted the number of interim visits with the counseling clinician, defined as those outside of the scheduled study visits. The average number for all participants at each site were computed. Site mean numbers were compared across treatments.

Acceptability - Number of Interim Medication Management Visits (COMB-R)

We counted the number of interim visits with the prescribing clinician, defined as those outside of the scheduled study visits. We computed the average number of sessions for all participants at each site. We took the mean of those averages.

COMB-R and ESC Acceptability Among Participants

Client satisfaction was computed as the mean of the 8 questionnaire items. Each is rated on a 4-point Likert scale from 1-4, with 4 being the best acceptability. Items reflected quality of service, degree to which program met participant needs, and satisfaction with and efficacy of the help given. The average score for all participants at each site was computed. Site mean scores were compared across treatments.

COMB-R and ESC Acceptability Among Counseling Clinicians

Six items were rated on a 4-point Likert scale from 0-3 (0=poor, 1=fair, 2=good, 3=excellent). A higher score indicates better clinician satisfaction with administering the intervention. These questions rated appropriateness, effectiveness, flexibility, ease of use, fit and overall quality of the treatment approach. For each participant's clinician, a mean score of the six items was computed. The average score was computed for the clinicians of all participants at each site. These site-level means were compared between groups.

COMB-R MM and ESC Acceptability Among Prescribing Clinicians

For each participant's prescribing clinician, we assessed two domains: How easy or difficult it was to follow the treatment plan (ESC) or medication management algorithm (COMB-R) and whether or not participants symptoms improved over the intervention period. These items were assessed on a 5-point Likert scale (0, 1, 2, 3, 4) and reverse scored if necessary so that a higher score reflected that it was easier to follow the algorithm and that the patients' symptoms improved. Average scores at each site were computed and the site-level summaries were compared across treatments.

Grade 3 or Higher Adverse Events (AE), Psychological Hospitalizations, and Suicide Attempts

In this analysis only "new" events were counted; as identified by MedDRA Preferred Term; that is, those which were first reported after study entry. Two types of adverse events were reported: 1) grade 3 or higher signs/symptoms, and 2) grade 3 or higher diagnoses. "Trigger" events (psychiatric hospitalization or suicide attempts) were also reported. For each of these three types of events, the percent of participants at each site with at least one such event was computed. The average of these site-level percentages within each treatment arm were compared. Note, in some cases due to sparseness (few events reported at sites within a treatment group), the lower bound of the 95% confidence interval was less than zero . In those cases, the bounds were truncated to zero.

Grade 3 or Higher Adverse Events (AE), Psychological Hospitalizations, and Suicide Attempts

n this analysis only "new" events were counted; as identified by MedDRA Preferred Term; that is, those which were first reported after study entry. Two types of adverse events were reported: 1) grade 3 or higher signs/symptoms, and 2) grade 3 or higher diagnoses. "Trigger" events (psychiatric hospitalization or suicide attempts) were also reported. For each of these three types of events, the percent of participants at each site with at least one such event was computed. The average of these site-level percentages within each treatment arm were compared. Note, in some cases due to sparseness (few events reported at sites within a treatment group), the lower bound of the 95% confidence interval was less than zero . In those cases, the bounds were truncated to zero.

Full Information

NCT ID

NCT02939131

First Posted

October 7, 2016

Last Updated

March 2, 2021

Sponsor

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Mental Health (NIMH)

1. Study Identification

Unique Protocol Identification Number

NCT02939131

Brief Title

IMPAACT 2002: Cognitive Behavioral Therapy and Medication Management for Treatment of Depression in US Youth With HIV

Official Title

IMPAACT 2002: Combined Cognitive Behavioral Therapy and a Medication Management Algorithm for Treatment of Depression Among Youth Living With HIV in the United States

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Completed

Study Start Date

March 6, 2017 (Actual)

Primary Completion Date

September 12, 2019 (Actual)

Study Completion Date

January 21, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

IMPAACT 2002 is a prospective, multi-site, two-arm, cluster-randomized study to evaluate whether a health and wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention for depression demonstrates improved depression and medical outcomes for HIV-infected youth in the United States (US) compared to enhanced standard care (ESC).

Detailed Description

IMPAACT 2002 was a prospective, multi-site, two-arm, cluster-randomized study that evaluated whether a health and wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention for depression demonstrated improved depression outcomes (e.g., decreased depressive symptoms and greater remission and response rates) and medical outcomes (e.g., increased cluster of differentiation 4 (CD4) T-cell count, decreased HIV RNA level) among HIV-infected youth in the US compared to enhanced standard care (ESC). Sites were randomized to either the COMB-R intervention or the ESC control arm. Youth enrolled in the study attended a Screening/Entry Visit and study visits at Weeks 1, 6, 12, and 24. They had two additional follow-up visits at Weeks 36 and 48 for the study team to evaluate if observed effects of the intervention were maintained. The intervention was a treatment for depression that included a manualized Health and Wellness Cognitive Behavioral Therapy and an algorithm-driven Medication Management designed to address the unique challenges faced by this population.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV, Depression

Keywords

Cognitive Behavioral Therapy, Medication Management

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

156 (Actual)

8. Arms, Groups, and Interventions

Arm Title

COMB-R

Arm Type

Experimental

Arm Description

Health and Wellness Cognitive Behavioral Therapy and Medication Management (COMB-R) intervention

Arm Title

Enhanced Standard of Care

Arm Type

Active Comparator

Arm Description

Enhanced Standard of Care (ESC)

Intervention Type

Behavioral

Intervention Name(s)

Health and Wellness Combined Cognitive Behavioral Therapy and a Medication Management Algorithm

Intervention Description

Behavioral therapy based on a manualized approach developed specifically for youth living with both HIV and depression, using problem-solving, motivational interviewing and cognitive-behavioral strategies to decrease adherence obstacles and increase wellness. The medication management algorithm includes guidance for clinicians on strategies and tactics to treat depression in this population, including factors to consider when deciding on treatments (i.e., drug-drug interactions, side effects).

Intervention Type

Behavioral

Intervention Name(s)

Enhanced Standard of Care

Intervention Description

Ongoing psychopharmacological and psychosocial counseling and treatment for depression at HIV clinical treatment centers enhanced by providing clinicians with up-to-date information and didactic training on current principles for use of medication and psychotherapy in the treatment of depression.

Primary Outcome Measure Information:

Title

Depression Outcomes: Quick Inventory of Depression Symptomatology - Self Report (QIDS-SR) Score

Description

Time Frame

Week 24

Title

Depression Outcomes: Response to Treatment, Defined as a Decrease in QIDS-SR Score by >50%

Description

Time Frame

Week 0 and Week 24

Title

Depression Outcomes: Remission, Defined as a QIDS-SR Score <= 5

Description

Time Frame

Week 24

Title

Biological Outcomes: Cluster of Differentiation 4 (CD4) Cell Count at Week 24

Description

CD4 cell counts are cells/microL (uL). CD4 cell counts of all participants at a site were averaged. The averages were then analyzed.

Time Frame

Week 24

Title

Biological Outcomes: Plasma HIV RNA Level at Week 24

Description

Time Frame

Week 24

Secondary Outcome Measure Information:

Title

Adherence Outcomes: Adherence to Anti-HIV Medications - Number of Days in Last 30 With Any Missed Doses

Description

Time Frame

Weeks 24 and 48

Title

Adherence Outcomes: Adherence to Anti-HIV Medications - How Good Participant Was at Taking Medicines as Instructed

Description

Time Frame

Weeks 24 and 48

Title

Adherence Outcomes: Adherence to Anti-HIV Medications - How Often Did Participant Take Medications as Instructed

Description

Time Frame

Weeks 24 and 48

Title

Adherence Outcomes: Adherence to Psychiatric Medications - Number of Days in Last 30 With Any Missed Doses

Description

Time Frame

Weeks 24 and 48

Title

Adherence Outcomes: Adherence to Psychiatric Medications - How Good Participant Was at Taking Medications as Instructed

Description

Time Frame

Weeks 24 and 48

Title

Adherence Outcomes: Adherence to Psychiatric Medications - How Often Did Participant Take Medicines as Instructed

Description

Adherence to depression medications at each assessment for the first 24 weeks (during active treatment) and at 48 weeks, as measured by self-report for those participants taking depression medications. The third of three questions was how often the participant took medication correctly in the past 30 days. Response scales are Likert from 1 to 6, with a higher score indicating better adherence: 1=Never .... 6=Always. The average score for all participants at each site was computed and these site-level summaries were compared across treatments.

Time Frame

Weeks 24 and 48

Title

Adherence Outcomes: Adherence to Psychotherapy Sessions

Description

Time Frame

Weeks 1, 6, 12 and 24

Title

Adherence Outcomes: Adherence to COMB-R Medication Management Sessions

Description

Time Frame

Weeks 1, 6, 12 and 24

Title

Adherence Outcomes: Adherence to Study Visits

Description

Time Frame

Weeks 0, 1, 6, 12, 24, 36 and 48

Title

Depression Outcomes: Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) Score Over 48 Weeks.

Description

Time Frame

Week 48

Title

Depression Outcomes: Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) Response to Treatment Over 48 Weeks, Defined as a Decrease in QIDS-SR Score by > 50%

Description

Time Frame

Week 0 and Week 48

Title

Depression Outcomes: Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) Score Remission Over 48 Weeks

Description

Time Frame

Week 48

Title

Effect of Demographic, Behavioral, and Biological Modifiers on Depression Outcomes: Quick Inventory of Depression Symptomatology (QIDS-SR) Score

Description

Time Frame

Week 48

Title

Effect of Demographic, Behavioral, and Biological Modifiers on Depression Outcomes: Response to Treatment

Description

Time Frame

Week 0 and Week 48

Title

Effect of Demographic, Behavioral, and Biological Modifiers on Depression Outcomes: Remission

Description

Time Frame

Week 48

Title

Behavioral Risk Outcomes: Alcohol Use - Ever Used

Description

The percent of participants who reported ever using alcohol was computed for each site. These site-level percentages were compared across treatment groups.

Time Frame

Weeks 24 and 48

Title

Behavioral Risk- Alcohol Use - Past 3 Months Regular Use Frequency

Description

Time Frame

weeks 24 and 48

Title

Behavioral Risk - Alcohol Use - Number of Drinks Per Day

Description

Time Frame

weeks 24 and 48

Title

Behavioral Risk - Alcohol Use - Binge Drinking

Description

Time Frame

Weeks 24 and 48

Title

Behavioral Risk Outcomes: Tobacco Use- Ever Used

Description

The percent of participants reporting tobacco use (ever) was computed for each site and these site-level averages were compared across treatments.

Time Frame

Weeks 24 and 48

Title

Behavioral Risk - Tobacco Use - Past 3 Months Regular Use Frequency

Description

Time Frame

weeks 24 and 48

Title

Behavioral Risk Outcomes: Drug Use - Ever Used

Description

Time Frame

Weeks 24 and 48

Title

Behavioral Risk - Drug Use - Past 3 Months Regular Frequency of Use

Description

Time Frame

week 24 and 48

Title

Behavioral Risk Outcomes: Sex-Risk Behaviors - Sex as Exchange Commodity

Description

Time Frame

Weeks 24 and 48

Title

Behavioral Risk Outcomes: Sex-Risk Behaviors - Importance of Using Condom

Description

Time Frame

weeks 24 and 48

Title

Behavioral Risk- Sex Risk Behaviors - Confidence in Condom Use

Description

Time Frame

Week 24 and 48

Title

Behavioral Risk - Sex Risk Behaviors - Number of Sexual Partners in Past Three Months

Description

Time Frame

week 24 and 48

Title

Behavioral Risk - Sex Risk Behaviors. Low Use Frequency of Condom Use in Last Three Months - Main Partner

Description

Time Frame

week 24 and 48

Title

Behavioral Risk - Sex Risk Behavior - Low Use Frequency of Condom Use in Past 3 Months - Other Partner

Description

Time Frame

week 24 and 48

Title

To Describe the Implementation Fidelity at COMB-R Sites and the Counseling Strategies and Medication Patterns at ESC Sites: The Total Numbers of Counseling Sessions

Description

Time Frame

over 24 weeks

Title

Implementation Fidelity (COMB-R Sites) - Count of Participants Having Been Administered Various COMB-R Counseling Approaches

Description

Time Frame

over 24 Weeks

Title

Counseling Strategies (ESC Sites) - Count of Participants Having Been Administered Various ESC Counseling Approaches

Description

Time Frame

Over 24 weeks

Title

Implementation Fidelity (COMB-R Sites); Medication Management - Number of Sessions

Description

Time Frame

Over 24 Weeks

Title

Implemental Fidelity (COMB-R) - Medication Management - Stages

Description

Time Frame

week 1, 6, 12, 24

Title

Acceptability: Frequency of Psychiatric Medication Use - Percent of Participants on Psychiatric Medications

Description

Time Frame

week 24

Title

Acceptability - Frequency of Psychiatric Medication Use - Percent of Study Time on Psychiatric Medications Through Week 24

Description

Time Frame

over 24 weeks

Title

Acceptability: Number of Interim Visits - Counseling Sessions

Description

Time Frame

Over 24 Weeks

Title

Acceptability - Number of Interim Medication Management Visits (COMB-R)

Description

Time Frame

Over 24 weeks

Title

COMB-R and ESC Acceptability Among Participants

Description

Time Frame

Week 24

Title

COMB-R and ESC Acceptability Among Counseling Clinicians

Description

Time Frame

Week 24

Title

COMB-R MM and ESC Acceptability Among Prescribing Clinicians

Description

Time Frame

Week 24

Title

Grade 3 or Higher Adverse Events (AE), Psychological Hospitalizations, and Suicide Attempts

Description

Time Frame

Over 24 Weeks

Title

Grade 3 or Higher Adverse Events (AE), Psychological Hospitalizations, and Suicide Attempts

Description

Time Frame

Over 48 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

24 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Receiving mental health or HIV-related care at participating US IMPAACT site Confirmed HIV-1 Infection Aware of his or her HIV infection Per clinician assessment, primary diagnosis of nonpsychotic depression, including Major Depressive Disorder, Depression Not Otherwise Specified (NOS), or Dysthymia, as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV or DSM-V criteria Current depressive symptoms that warrant intervention as determined by a score of ≥ 11 on the Quick Inventory of Depressive Symptomatology - Clinician (QIDS-C) Able to communicate in spoken and written English Able and willing to provide written informed assent/consent and able to obtain written parental or guardian permission (if required, as specified in site standard operating procedure (SOP), by State law, and/or Institutional Review Board (IRB) policy) to be screened for and to enroll in IMPAACT 2002 Exclusion Criteria: Known or self-reported history of any psychotic disorder and/or bipolar I or II disorder Severe disorders (more than 6 symptoms) based on DSM-V criteria related to alcohol, cannabis or other substances; or those with moderate symptoms (4 or 5 symptoms) who are also currently experiencing withdrawal or dependence symptoms; within the past month prior to enrollment Per clinician assessment at screening, depression and/or suicidal ideation requiring more intensive treatment than the study provides or at immediate risk of being a danger to themselves or others Per participant report at screening, intends to relocate away from the study site during study participation Currently in therapy with a non-study provider, unless willing to switch to a study-trained provider Has any other condition that, in the opinion of the Investigator of Record (IoR)/designee, would preclude informed assent/consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Larry Brown, MD

Organizational Affiliation

Rhode Island Hospital; Brown University

Official's Role

Study Chair

Facility Information:

Facility Name

University of Southern California - MCA Center (CRS 5048),

City

Alhambra

State/Province

California

ZIP/Postal Code

91803

Country

United States

Facility Name

University California, San Diego (CRS 4601)

City

La Jolla

State/Province

California

ZIP/Postal Code

92093

Country

United States

Facility Name

David Geffen School of Medicine at UCLA (CRS 5112)

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Children's Hospital of Colorado (CRS 5052)

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

Children's Diagnostic and Treatment Center (CRS 5055)

City

Fort Lauderdale

State/Province

Florida

ZIP/Postal Code

33316

Country

United States

Facility Name

Emory University School of Medicine (CRS 5030)

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30308

Country

United States

Facility Name

Rush University Medical Center (CRS 5083)

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

Facility Name

Johns Hopkins University School of Medicine (CRS 5092)

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

Facility Name

Bronx-Lebanon Hospital Center (CRS 5114)

City

Bronx

State/Province

New York

ZIP/Postal Code

10457

Country

United States

Facility Name

Jacobi Medical Center (CRS 5013)

City

Bronx

State/Province

New York

ZIP/Postal Code

10461

Country

United States

Facility Name

Stony Brook University Medical Center (CRS 5040)

City

Stony Brook

State/Province

New York

ZIP/Postal Code

11794

Country

United States

Facility Name

St Jude Children's Research Hospital (CRS 6501)

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38105

Country

United States

Facility Name

Texas Children's/Baylor (CRS 3801)

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Individual participant data and related data dictionaries that underlie results in the publication will be shared after deidentification.

IPD Sharing Time Frame

Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.

IPD Sharing Access Criteria

With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT network, For what types of analyses? To achieve aims in the proposal approved by the IMPAACT network. By what mechanism will data be made available? Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/studies/submit-research-proposal. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.

IPD Sharing URL

https://www.impaactnetwork.org/studies/submit-research-proposal

Citations:

PubMed Identifier

26761270

Citation

Brown LK, Kennard BD, Emslie GJ, Mayes TL, Whiteley LB, Bethel J, Xu J, Thornton S, Tanney MR, Hawkins LA, Garvie PA, Subramaniam GA, Worrell CJ, Stoff LW; Adolescent Trials Network for HIVAIDS Interventions. Effective Treatment of Depressive Disorders in Medical Clinics for Adolescents and Young Adults Living With HIV: A Controlled Trial. J Acquir Immune Defic Syndr. 2016 Jan 1;71(1):38-46. doi: 10.1097/QAI.0000000000000803.

Results Reference

background

PubMed Identifier

20683845

Citation

Bernstein IH, Rush AJ, Trivedi MH, Hughes CW, Macleod L, Witte BP, Jain S, Mayes TL, Emslie GJ. Psychometric properties of the Quick Inventory of Depressive Symptomatology in adolescents. Int J Methods Psychiatr Res. 2010 Dec;19(4):185-94. doi: 10.1002/mpr.321.

Results Reference

background

Links:

URL

https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables

Description

The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (AE) (DAIDS AE Grading Table), Corrected Version 2.1, July 2017

URL

https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf

Description

Richard M Selik, Eve D Mokotoff, Bernard Branson, et al. Revised Surveillance Case Definition for HIV Infection - United States, 2014. Morbidity and Mortality Weekly Report (MMWR) 2014; 63 (No. 3):7

URL

http://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-reporting-adverse-events-daids

Description

Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS Expedited Adverse Events (EAE) Manual), Version 2.0, January 2010

Learn more about this trial

IMPAACT 2002: Cognitive Behavioral Therapy and Medication Management for Treatment of Depression in US Youth With HIV

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IMPAACT 2002: Cognitive Behavioral Therapy and Medication Management for Treatment of Depression in US Youth With HIV

HIV, Depression

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial