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SSRI Effects on Depression and Immunity in HIV/AIDS

Primary Purpose

Depression, HIV, AIDS

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Escitalopram

Placebo

About this trial

This is an interventional treatment trial for Depression focused on measuring HIV, AIDS, Depression, SSRI, Escitalopram, Immunity

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Men and women aged 18-70 years, of any race and ethnicity,
HIV-seropositive by ELISA and Western Blot assays, infected by behavioral transmission (perinatal HIV excluded),
Willing and able to comply with antidepressant medication regimen and scheduled follow-up visits,
Currently on a documented regimen of cART for at least 3 months and Viral load less than 200 copies/ml,
Current depressive symptoms (HAM-D-17 score ≥ 13 and a SCID diagnosis of either Major Depressive Disorder, Persistent Depressive Disorder (Dysthymia), Unspecified Depressive Disorder, or Other Specified Depressive Disorder)
Able to understand and provide informed consent.

Exclusion Criteria:

Acute suicidal ideation, gestures, or attempts (e.g., HAM-D suicide item score of 3 "Ideas or gestures of suicide" or 4 "Attempts at suicide" at intake or HAM-D suicide item score of 4 "Attempts at suicide" during study),
Significant cognitive impairment or dementia including HIV Associated Dementia (HAD),
Use of a medication known to alter immune function within 4 weeks prior to randomization (the following are not excluded: a. acyclovir and related antiviral medications, b. topical corticosteroids, c. corticosteroid nasal sprays or inhalers, d) statin medications,),
Immunization with HIV vaccine,
Presence of psychotic symptoms or known diagnosis of a primary psychotic disorder,
Currently taking an anti-psychotic medication,
Pregnant or within nine months post-delivery, lactation,
Current or chronic medical condition that would likely preclude adherence to protocol or completion of the trial (per investigator judgment),
Bipolar disorder (I or II) or schizophrenia,
Current pharmacotherapy for treatment of depression,
A history of intolerance or nonresponse to an adequate trial of escitalopram (or other SSRIs),
Renal failure, including those who require dialysis,
History of epilepsy or seizure disorder,
Taken MAOIs within 14 days,
On the antibiotic Linezolid and taking IV methylene blue,
On a regular regime of medication known to have anticoagulant properties such as NSAID, aspirin or warfarin,
A history of acute narrow/closed angle glaucoma,
Currently taking CNS drugs (the following are not excluded: gabapentin, pregabalin, varenicline, antihistamines, and hypnotics (e.g. zolpidem, zaleplon, eszopiclone),
On any triptan medications,
Undergoing ECT.

Sites / Locations

University of Pennsylvania Perelman School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental

Placebo

Arm Description

CCBT plus Escitalopram, oral, for 10 weeks, once daily, starting at 10mg/day. Tapered up or down, based on tolerability and clinical response, to 20mg/day max.

CCBT plus Placebo, oral, for 10 weeks, once daily, starting at 10mg/day. Tapered up or down, based on tolerability and clinical response, to 20mg/day max.

Outcomes

Primary Outcome Measures

SSRI Effects on Change of Natural Killer Cell Activity (LUNK), Determined by Biological Assay, Units are LU20 PBMC and LU20 NK .

Description of Units: LU20 PBMC is the number of effector cells required to achieve 20% lysis of target cells per ten million peripheral blood mononuclear cells (PBMC). LU20 NK is the number of effector cells required to achieve 20% lysis of target cells per ten million natural killer cells (NK).

SSRI Effects on Change of Intracellular Interferon Gamma (IFN-g), Determined by Biological Assay, (% of Natural Killer Cells producing IFN-g).

% of Natural Killer Cells producing IFN-g

SSRI Effects on Change of Plasma Interleukin 6 (IL-6), Determined by Biological Assay, pg/mL.

pg/mL

SSRI Effects on Change of Plasma C-Reactive Protein (CRP), Determined by Biological Assay, (mg/L)

mg/L

Secondary Outcome Measures

Depression Improvement Effects on Change of Natural Killer Cell Activity (LUNK), Determined by Biological Assay, Units are LU20 PBMC and LU20 NK.

Depression Improvement Effects on Change of Intracellular Interferon Gamma (IFN-g), Determined by Biological Assay, (% of Natural Killer Cells producing IFN-g).

% of Natural Killer Cells producing IFN-g

Depression Improvement Effects on Change of Plasma Interleukin 6 (IL-6), Determined by Biological assay, (pg/mL).

pg/mL

Depression Improvement Effects on Change of Plasma C-Reactive Protein (CRP), Determined by Biological Assay, (mg/L).

mg/L

Full Information

NCT ID

NCT02620150

First Posted

November 20, 2015

Last Updated

June 23, 2022

Sponsor

University of Pennsylvania

1. Study Identification

Unique Protocol Identification Number

NCT02620150

Brief Title

SSRI Effects on Depression and Immunity in HIV/AIDS

Official Title

SSRI Effects on Depression and Immunity in HIV/AIDS

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Completed

Study Start Date

February 16, 2017 (Actual)

Primary Completion Date

March 31, 2022 (Actual)

Study Completion Date

March 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Pennsylvania

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a 10 week, double-blind, placebo controlled trial to evaluate SSRI (Selective Serotonin Reuptake Inhibitor) effects for treatment of depression in HIV/AIDS with a focus on innate immunity and inflammation. Depressed population is HIV + on cART (Combination Antiretroviral Therapy), not currently on pharmacotherapy for depression. Subjects will complete computerized cognitive behavior therapy, CCBT for their depression. Blood samples collected for virologic, neuroendocrine, and immunologic evaluation. Our overarching hypothesis is that SSRI treatment of depression and improvement of depressive symptoms leads to increased innate immunity and decreased inflammation, resulting in better control of HIV disease and decreased morbidity.

Detailed Description

To pursue our long-term objective of successfully treating co-morbid mental and medical disorders in HIV/AIDS, this study aims to determine whether: 1) SSRI treatment significantly increases innate immunity and decreases chronic inflammation and immune activation, and 2) changes in depressive symptoms correlate with changes in immunity in HIV/AIDS. HIV-seropositive, depressed subjects will be randomized to 10 weeks of double blind therapy with either escitalopram or placebo. All participants will concurrently begin CCBT (Computerized Cognitive Behavioral Therapy) using the program Good Days Ahead. Subject visits will occur weekly for the first 6 weeks and then at weeks 8 and 10. The treating clinician will assess side effects, review symptomatic progress, and adjust the study medication as clinically appropriate. An independent clinical evaluator will assess patients at baseline, and weeks 1-6, 8 and 10. Blood samples collected at baseline and weeks 2, 4, and 10 will be used to assay markers of innate immune suppression (lytic units of NK cells, LUNK, and intracellular IFN gamma in NK cells) and markers of inflammation (IL-6 and C-Reactive Protein). At the end of the 10-week treatment phase, all participants will be referred for appropriate clinical treatment of their depression.

6. Conditions and Keywords

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

Depression, HIV, AIDS

Keywords

HIV, AIDS, Depression, SSRI, Escitalopram, Immunity

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

108 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Experimental

Arm Type

Experimental

Arm Description

CCBT plus Escitalopram, oral, for 10 weeks, once daily, starting at 10mg/day. Tapered up or down, based on tolerability and clinical response, to 20mg/day max.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

CCBT plus Placebo, oral, for 10 weeks, once daily, starting at 10mg/day. Tapered up or down, based on tolerability and clinical response, to 20mg/day max.

Intervention Type

Drug

Intervention Name(s)

Escitalopram

Intervention Description

10 week trial

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

10 week trial

Primary Outcome Measure Information:

Title

SSRI Effects on Change of Natural Killer Cell Activity (LUNK), Determined by Biological Assay, Units are LU20 PBMC and LU20 NK .

Description

Time Frame

10 weeks

Title

SSRI Effects on Change of Intracellular Interferon Gamma (IFN-g), Determined by Biological Assay, (% of Natural Killer Cells producing IFN-g).

Description

% of Natural Killer Cells producing IFN-g

Time Frame

2 weeks, 4 weeks, 10 weeks

Title

SSRI Effects on Change of Plasma Interleukin 6 (IL-6), Determined by Biological Assay, pg/mL.

Description

pg/mL

Time Frame

2 weeks, 4 weeks, 10 weeks

Title

SSRI Effects on Change of Plasma C-Reactive Protein (CRP), Determined by Biological Assay, (mg/L)

Description

mg/L

Time Frame

2 weeks, 4 weeks, 10 weeks

Secondary Outcome Measure Information:

Title

Depression Improvement Effects on Change of Natural Killer Cell Activity (LUNK), Determined by Biological Assay, Units are LU20 PBMC and LU20 NK.

Description

Time Frame

10 weeks

Title

Depression Improvement Effects on Change of Intracellular Interferon Gamma (IFN-g), Determined by Biological Assay, (% of Natural Killer Cells producing IFN-g).

Description

% of Natural Killer Cells producing IFN-g

Time Frame

2 weeks, 4 weeks, 10 weeks

Title

Depression Improvement Effects on Change of Plasma Interleukin 6 (IL-6), Determined by Biological assay, (pg/mL).

Description

pg/mL

Time Frame

2 weeks, 4 weeks, 10 weeks

Title

Depression Improvement Effects on Change of Plasma C-Reactive Protein (CRP), Determined by Biological Assay, (mg/L).

Description

mg/L

Time Frame

2 weeks, 4 weeks, 10 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Men and women aged 18-70 years, of any race and ethnicity, HIV-seropositive by ELISA and Western Blot assays, infected by behavioral transmission (perinatal HIV excluded), Willing and able to comply with antidepressant medication regimen and scheduled follow-up visits, Currently on a documented regimen of cART for at least 3 months and Viral load less than 200 copies/ml, Current depressive symptoms (HAM-D-17 score ≥ 13 and a SCID diagnosis of either Major Depressive Disorder, Persistent Depressive Disorder (Dysthymia), Unspecified Depressive Disorder, or Other Specified Depressive Disorder) Able to understand and provide informed consent. Exclusion Criteria: Acute suicidal ideation, gestures, or attempts (e.g., HAM-D suicide item score of 3 "Ideas or gestures of suicide" or 4 "Attempts at suicide" at intake or HAM-D suicide item score of 4 "Attempts at suicide" during study), Significant cognitive impairment or dementia including HIV Associated Dementia (HAD), Use of a medication known to alter immune function within 4 weeks prior to randomization (the following are not excluded: a. acyclovir and related antiviral medications, b. topical corticosteroids, c. corticosteroid nasal sprays or inhalers, d) statin medications,), Immunization with HIV vaccine, Presence of psychotic symptoms or known diagnosis of a primary psychotic disorder, Currently taking an anti-psychotic medication, Pregnant or within nine months post-delivery, lactation, Current or chronic medical condition that would likely preclude adherence to protocol or completion of the trial (per investigator judgment), Bipolar disorder (I or II) or schizophrenia, Current pharmacotherapy for treatment of depression, A history of intolerance or nonresponse to an adequate trial of escitalopram (or other SSRIs), Renal failure, including those who require dialysis, History of epilepsy or seizure disorder, Taken MAOIs within 14 days, On the antibiotic Linezolid and taking IV methylene blue, On a regular regime of medication known to have anticoagulant properties such as NSAID, aspirin or warfarin, A history of acute narrow/closed angle glaucoma, Currently taking CNS drugs (the following are not excluded: gabapentin, pregabalin, varenicline, antihistamines, and hypnotics (e.g. zolpidem, zaleplon, eszopiclone), On any triptan medications, Undergoing ECT.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dwight L Evans, MD

Organizational Affiliation

University of Pennsylvania

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Pennsylvania Perelman School of Medicine

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

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SSRI Effects on Depression and Immunity in HIV/AIDS

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