Back to resultsIntramuscular Ketamine Versus Aripiprazole and Escitalopram in the Treatment of Resistant Depression (KETProject)
Primary Purpose
Depressive Disorder
Status
Unknown status
Phase
Phase 4
Locations
Brazil
Study Type
Interventional
Intervention
Ketamine
Cognition
Suicide risk
Depression thoughts
Quality of life and disability
Clinical and epidemiological factors
Safety of ketamine IM
Tolerability of ketamine IM
Sponsored by
About this trial
This is an interventional treatment trial for Depressive Disorder focused on measuring Ketamine, Treatment Resistant Depression
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of TRD, according to clinical evaluation and confirmed by SCID-IV (Structured Clinical Interview for the DSM);
- Moderate to severe intensity of the disease;
Female patients in fertile conditions should be using a clinically accepted contraceptive method (oral contraceptive and/or condom);
a. Blood test will be requested at the diagnostic stage and in case of clinical doubt as to the patient's gestational status,
- Literate and able to understand the tasks requested;
- With clinical comorbidities, however compensated;
- Patients and/or legal representatives should understand the nature of the study and sign the Informed Consent Form.
Exclusion Criteria:
- Imminent risk of suicide;
- Patients with psychoactive substance dependence;
- Intellectual deficit and psychotic symptoms;
- Bipolar spectrum disorders and other primary psychiatric diagnoses;
- Allergic to ketamine;
- Glaucoma;
- Treatment with reversible MAOI (monoamine oxidase inhibitor) in the week prior to visit 0;
- Treatment with irreversible MAOI in two weeks prior to visit 0;
- Fluoxetine treatment within 4 weeks prior to visit 0;
- Treatment with others antidepressants;
Treatment with antipsychotics, lithium, benzodiazepines or other psychotropic drugs within 7 days prior to visit 0;
a. Lorazepam and zolpidem may be used;
- Patients who become pregnant will be excluded from the study and referred for obstetric care.
Sites / Locations
- Núcleo de Pesquisas em Saúde Mental
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Rapid-acting antidepressant
Comparator
Arm Description
Subjects eligible to participate in the study will receive IM ketamine and will use 2 placebo tablets as randomized.
Subjects eligible to participate in the study will receive IM saline and will use escitalopram 15 mg and aripiprazole 5 mg as randomized
Outcomes
Primary Outcome Measures
Change in depressive symptoms
Montomery-Åsberg Depression Rating Scale ([0-60] higher scores: worse outcome). No improvement: MADRS ≤ 25% Partial response: MADRS ≥ 25% and < 50% Response: MADRS ≥ 50% Remission: MADRS ≤10
Change in depressive symptoms
Montgomery-Åsberg Depression Rating Scale ([0-60] higher scores: worse outcome).
Recovery: Maintenance ≥ 6-8 months Relapse: Full return of symptoms once remission has occurred or worsening ≤ 75% with lower percentage of improvement (HAM-D inclusion criteria)
Change in depressive symptoms
Montgomery-Åsberg Depression Rating Scale ([0-60] higher scores: worse outcome).
Relapse: Full return of symptoms once remission has occurred or worsening ≤ 75% with lower percentage of improvement (HAM-D inclusion criteria).
Secondary Outcome Measures
Depression symptoms
Hamiltom Depression Ratins Scale (HAM-D [0-50] higher scores: worse outcome).
Clinical impressions-S
Clinical Global Impression Scale (CGI [0-7] higher scores: worse outcome).
Clinical impressions-I
Clinical Global Impression Scale (CGI [0-7] higher scores: worse outcome).
Electrocardiographic monitoring
P wave, PR interval, QRS complex, J-point, ST segment, T wave, Corrected QT interval and U wave Rhythm (irregular rhythm: worse outcome).
Blood Pressure (BP [mmHg]).
BP low <90/60 (systolic/diastolic) mmHg and high >140/90 mmHg ( (systolic/diastolic).
Heart rate (HR [bpm]).
Anormal HR <60 bpm or >100 bpm.
Digital pulse oximetry (%).
Low oxygen saturation <95%.
Respiratory rate (RR [cycles/min])
Anormal RR <10 cycles/min or >20 cycles/min.
Suicide risk 1
Montgomery-Åsberg Depression Rating Scale (item 10 [0-6] higher scores: worse outcome).
Suicide risk 2
Hamilton Depression Rating Scale (item 3 [0-4] higher scores: worse outcome).
General side effects
Ugvalg for Kliniske Undersgelser-Side Effect Rating Scale (UKU-SERS [48 specific symptoms).
Hypo/maniac symptoms
Young Mania Rating Scale (YOUNG [0-58] higher scores: worse outcome).
Dissociative symptoms
Clinician-Administered Dissociative State Scale (CADSS [0-108] higher scores: worse outcome)
Psychotic symptoms
Brief Psychiatric Rating Scale (item 12 [0-6] higher scores: worse outcome).
Depression thoughts
Depression Thoughts Scale (EPD [1-78] higher scores: worse outcome)
Stimate intelligence quocient
Wechsler Abreviated Scale of Intelligence (WASI [70-160 percentille] higher scores: better outcomes).
Intelligence quocient
Wechsler Scale of Intelligence (WAIS III [70-155 percentille] higher scores: better outcomes).
Attention
Trial Making Test (5-95 percentille, higher scores: better outcomes).
Memory
Rey figures (10-100 percentille, higher scores: better outcomes)
Executive functions 1
Wisconsin Test (50->80 score, higher scores: better outcomes).
Executive functions 2
Stroop Color Word Test (5-95 percentille, higher scores: better outcomes)
Verbal fluency 1
Verbal Fluency Test (FAS [10-90 percentille], higher scores: better outcomes))
Verbal fluency 2
The Rey Auditory-Verbal Learning Test (RAVLT [5-95 percentille], higher scores: better outcomes).
Functional recovery 1
World Health Organization Quality of Life (WHOQOL-brief [4 domains, 26 questions higher scores: better outcome]).
Functional recovery 2
Sheehan Disability Scale (SDS [0-30] higher scores: worse outcome).
Body Mass Index (BMI)
Weight and height (kg/m2).
Clinical and psychiatric features 1
Disease intensity (HAM-D [% of patients], moderate or severe)
Clinical and psychiatric features 2
Number of episodes (questionnaire [incidence])
Clinical and psychiatric features 3
Current episode duration (questionnaire [years])
Clinical and psychiatric features 4
Suicide attempts (questionnaire [% of pacients])
Clinical and psychiatric features 5
History of physical abuse (questionnaire [% of pacients])
Clinical and psychiatric features 6
History of sexual abuse (questionnaire [% of pacients])
Clinical and psychiatric features 7
Psychiatric hospitalizations (questionnaire [% of pacients])
Clinical and psychiatric features 8
Clinical comorbidities (questionnaire [% of patients]).
Clinical and psychiatric features 9
Family history of depression (questionnaire [% of patients])
Clinical and psychiatric features 10
Family history of bipolar disorders (questionnaire [% of patients)
Clinical and psychiatric features 11
Family history of other mental disorders (questionnaire [% of patients]).
Epidemiological features 1
Age (questionnaire [years]).
Epidemiological features 2
Gender (questionnaire [% of patients]; male/female)
Epidemiological features 3
Marital status (questionnaire [% of patients] single, married, separated, divorced or widower).
Epidemiological features 4
Ethnicity (questionnaire [% of patients])
Epidemiological features 5
Religion (questionnaire [% of patients] protestant, pentecostal or neopentecostal, spiritism, afro-brazilian, no religion or atheism and others]).
Epidemiological features 6
Occupation (questionnaire [% of patients])
Epidemiological features 7
Education (questionnaire [years])
Epidemiological features 8
Individual income (questionnaire [dollars]).
Epidemiological features 9
Family income (questionnaire [dollars]).
Full Information
NCT ID
NCT04234776
First Posted
October 7, 2019
Last Updated
January 15, 2020
Sponsor
University of Sao Paulo
1. Study Identification
Unique Protocol Identification Number
NCT04234776
Brief Title
Intramuscular Ketamine Versus Aripiprazole and Escitalopram in the Treatment of Resistant Depression
Acronym
KETProject
Official Title
Intramuscular Ketamine Versus Escitalopram and Aripiprazole in Acute and Maintenance Treatment of Patients With Treatment-resistant Depression
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Unknown status
Study Start Date
April 3, 2018 (Actual)
Primary Completion Date
June 3, 2020 (Anticipated)
Study Completion Date
April 3, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Sao Paulo
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The treatment of resistant depression should be optimized aiming at complete remission of symptoms, a complex condition due to several factors. Approximately 1/3 of patients with depressive disorders do not even respond to available antidepressants. Consequently, new molecules with robust action, fast effects and sustained improvement are currently being researched worldwide. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has emerged as a promising alternative due to its involvement in neurogenesis, synaptogenesis and consequent rapid improvement of depressive and suicidal symptoms with traditional intravenous (IV) use in sub dose (0.5 mg / kg). The therapeutic response of IV use has been short and requires monitoring in a hospital setting. There are no studies evaluating response to long-term ketamine use. Recent research has focused on identifying other routes of ketamine use such as intranasal and intramuscular (IM). The use of ketamine IM, despite the fact that there are few studies and small samples, can demonstrate efficacy in acute treatment and maintenance of depression, as well as low profile of side effects, greater accessibility potential, reduced costs and risks, patient comfort and possible expansion of resistant depression treatment capabilities in different settings.
Detailed Description
Compare the response of ketamine IM versus active control in treatment-resistant depression (TRD [primary outcome]) and find safety and tolerability of ketamine IM, evaluate changes in life quality, cognition and suicidal risk (secondary outcomes)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depressive Disorder
Keywords
Ketamine, Treatment Resistant Depression
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Subjects will receive IM ketamine or IM saline applications as randomized. Applications will occur three times a week. It will be 4 weeks of IM application (12 initial applications). Injections will occur into the subjects' glutes (0.75 mg / kg). The ketamine group will use 2 placebo tablets and the parallel group escitalopram 15 mg and aripiprazole 5 mg. Thereafter, participants will receive weekly ketamine doses over 6 months as maintenance treatment. Research members will be submitted to Structured Clinical Interview for the DSM for diagnostic categorization and will be evaluated from other scales. Vital signs will be checked continuously for a period of 2 hours with each infusion. Patients will be observed in a quiet, comfortable room and subjected to medical monitoring for 2 hours. They will leave the environment in the company of a competent adult.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
88 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Rapid-acting antidepressant
Arm Type
Experimental
Arm Description
Subjects eligible to participate in the study will receive IM ketamine and will use 2 placebo tablets as randomized.
Arm Title
Comparator
Arm Type
Active Comparator
Arm Description
Subjects eligible to participate in the study will receive IM saline and will use escitalopram 15 mg and aripiprazole 5 mg as randomized
Intervention Type
Drug
Intervention Name(s)
Ketamine
Other Intervention Name(s)
Active comparator (escitalopram plus aripiprazole), Placebo
Intervention Description
(0,75 mg/kg) saline solution (15 mg) Escitalopram (5 mg) Aripiprazole
Intervention Type
Diagnostic Test
Intervention Name(s)
Cognition
Intervention Description
Composite tools
Intervention Type
Other
Intervention Name(s)
Suicide risk
Intervention Description
MADRS (10) and HAM-D (3)
Intervention Type
Other
Intervention Name(s)
Depression thoughts
Intervention Description
EPD
Intervention Type
Other
Intervention Name(s)
Quality of life and disability
Intervention Description
Quality of life and disability
Intervention Type
Other
Intervention Name(s)
Clinical and epidemiological factors
Intervention Description
Variables and categories
Intervention Type
Device
Intervention Name(s)
Safety of ketamine IM
Intervention Description
Vital signs
Intervention Type
Other
Intervention Name(s)
Tolerability of ketamine IM
Intervention Description
UKU-SERS, YOUNG, CADSS and BPRS-12.
Primary Outcome Measure Information:
Title
Change in depressive symptoms
Description
Montomery-Åsberg Depression Rating Scale ([0-60] higher scores: worse outcome). No improvement: MADRS ≤ 25% Partial response: MADRS ≥ 25% and < 50% Response: MADRS ≥ 50% Remission: MADRS ≤10
Time Frame
3 times a week in once month (Phase II)
Title
Change in depressive symptoms
Description
Montgomery-Åsberg Depression Rating Scale ([0-60] higher scores: worse outcome).
Recovery: Maintenance ≥ 6-8 months Relapse: Full return of symptoms once remission has occurred or worsening ≤ 75% with lower percentage of improvement (HAM-D inclusion criteria)
Time Frame
Once a week in six months (Phase III)
Title
Change in depressive symptoms
Description
Montgomery-Åsberg Depression Rating Scale ([0-60] higher scores: worse outcome).
Relapse: Full return of symptoms once remission has occurred or worsening ≤ 75% with lower percentage of improvement (HAM-D inclusion criteria).
Time Frame
Once a week in once month (Phase IV)
Secondary Outcome Measure Information:
Title
Depression symptoms
Description
Hamiltom Depression Ratins Scale (HAM-D [0-50] higher scores: worse outcome).
Time Frame
Through study completion, an average of 1 year.
Title
Clinical impressions-S
Description
Clinical Global Impression Scale (CGI [0-7] higher scores: worse outcome).
Time Frame
Through study completion, an average of 1 year.
Title
Clinical impressions-I
Description
Clinical Global Impression Scale (CGI [0-7] higher scores: worse outcome).
Time Frame
Through study completion, an average of 1 year.
Title
Electrocardiographic monitoring
Description
P wave, PR interval, QRS complex, J-point, ST segment, T wave, Corrected QT interval and U wave Rhythm (irregular rhythm: worse outcome).
Time Frame
3 times a week in once month (Fase II) and once a week in six months (Phase III)
Title
Blood Pressure (BP [mmHg]).
Description
BP low <90/60 (systolic/diastolic) mmHg and high >140/90 mmHg ( (systolic/diastolic).
Time Frame
3 times a week in once month (Fase II) and once a week in six months (Phase III)
Title
Heart rate (HR [bpm]).
Description
Anormal HR <60 bpm or >100 bpm.
Time Frame
3 times a week in once month (Fase II) and once a week in six months (Phase III)
Title
Digital pulse oximetry (%).
Description
Low oxygen saturation <95%.
Time Frame
3 times a week in once month (Fase II) and once a week in six months (Phase III)
Title
Respiratory rate (RR [cycles/min])
Description
Anormal RR <10 cycles/min or >20 cycles/min.
Time Frame
3 times a week in once month (Fase II) and once a week in six months (Phase III)
Title
Suicide risk 1
Description
Montgomery-Åsberg Depression Rating Scale (item 10 [0-6] higher scores: worse outcome).
Time Frame
Through study completion, an average of 1 year.
Title
Suicide risk 2
Description
Hamilton Depression Rating Scale (item 3 [0-4] higher scores: worse outcome).
Time Frame
Through study completion, an average of 1 year.
Title
General side effects
Description
Ugvalg for Kliniske Undersgelser-Side Effect Rating Scale (UKU-SERS [48 specific symptoms).
Time Frame
3 times a week in once month (Phase II) and once a week in six months (Phase III)
Title
Hypo/maniac symptoms
Description
Young Mania Rating Scale (YOUNG [0-58] higher scores: worse outcome).
Time Frame
3 times a week in once month (Phase II) and once a week in six months (Phase III)
Title
Dissociative symptoms
Description
Clinician-Administered Dissociative State Scale (CADSS [0-108] higher scores: worse outcome)
Time Frame
3 times a week in once month (Phase II) and once a week in six months (Phase III)
Title
Psychotic symptoms
Description
Brief Psychiatric Rating Scale (item 12 [0-6] higher scores: worse outcome).
Time Frame
3 times a week in once month (Phase II) and once a week in six months (Phase III)
Title
Depression thoughts
Description
Depression Thoughts Scale (EPD [1-78] higher scores: worse outcome)
Time Frame
Through study completion, an average of 1 year.
Title
Stimate intelligence quocient
Description
Wechsler Abreviated Scale of Intelligence (WASI [70-160 percentille] higher scores: better outcomes).
Time Frame
Through study completion, an average of 1 year.
Title
Intelligence quocient
Description
Wechsler Scale of Intelligence (WAIS III [70-155 percentille] higher scores: better outcomes).
Time Frame
Through study completion, an average of 1 year.
Title
Attention
Description
Trial Making Test (5-95 percentille, higher scores: better outcomes).
Time Frame
Through study completion, an average of 1 year.
Title
Memory
Description
Rey figures (10-100 percentille, higher scores: better outcomes)
Time Frame
Through study completion, an average of 1 year.
Title
Executive functions 1
Description
Wisconsin Test (50->80 score, higher scores: better outcomes).
Time Frame
Through study completion, an average of 1 year.
Title
Executive functions 2
Description
Stroop Color Word Test (5-95 percentille, higher scores: better outcomes)
Time Frame
Through study completion, an average of 1 year.
Title
Verbal fluency 1
Description
Verbal Fluency Test (FAS [10-90 percentille], higher scores: better outcomes))
Time Frame
Through study completion, an average of 1 year.
Title
Verbal fluency 2
Description
The Rey Auditory-Verbal Learning Test (RAVLT [5-95 percentille], higher scores: better outcomes).
Time Frame
Through study completion, an average of 1 year.
Title
Functional recovery 1
Description
World Health Organization Quality of Life (WHOQOL-brief [4 domains, 26 questions higher scores: better outcome]).
Time Frame
Through study completion, an average of 1 year.
Title
Functional recovery 2
Description
Sheehan Disability Scale (SDS [0-30] higher scores: worse outcome).
Time Frame
Through study completion, an average of 1 year.
Title
Body Mass Index (BMI)
Description
Weight and height (kg/m2).
Time Frame
Through study completion, an average of 1 year.
Title
Clinical and psychiatric features 1
Description
Disease intensity (HAM-D [% of patients], moderate or severe)
Time Frame
Through study completion, an average of 1 year.
Title
Clinical and psychiatric features 2
Description
Number of episodes (questionnaire [incidence])
Time Frame
Through study completion, an average of 1 year.
Title
Clinical and psychiatric features 3
Description
Current episode duration (questionnaire [years])
Time Frame
Through study completion, an average of 1 year.
Title
Clinical and psychiatric features 4
Description
Suicide attempts (questionnaire [% of pacients])
Time Frame
Through study completion, an average of 1 year.
Title
Clinical and psychiatric features 5
Description
History of physical abuse (questionnaire [% of pacients])
Time Frame
Through study completion, an average of 1 year.
Title
Clinical and psychiatric features 6
Description
History of sexual abuse (questionnaire [% of pacients])
Time Frame
Through study completion, an average of 1 year.
Title
Clinical and psychiatric features 7
Description
Psychiatric hospitalizations (questionnaire [% of pacients])
Time Frame
Through study completion, an average of 1 year.
Title
Clinical and psychiatric features 8
Description
Clinical comorbidities (questionnaire [% of patients]).
Time Frame
Through study completion, an average of 1 year.
Title
Clinical and psychiatric features 9
Description
Family history of depression (questionnaire [% of patients])
Time Frame
Through study completion, an average of 1 year.
Title
Clinical and psychiatric features 10
Description
Family history of bipolar disorders (questionnaire [% of patients)
Time Frame
Through study completion, an average of 1 year.
Title
Clinical and psychiatric features 11
Description
Family history of other mental disorders (questionnaire [% of patients]).
Time Frame
Through study completion, an average of 1 year.
Title
Epidemiological features 1
Description
Age (questionnaire [years]).
Time Frame
Through study completion, an average of 1 year.
Title
Epidemiological features 2
Description
Gender (questionnaire [% of patients]; male/female)
Time Frame
Through study completion, an average of 1 year.
Title
Epidemiological features 3
Description
Marital status (questionnaire [% of patients] single, married, separated, divorced or widower).
Time Frame
Through study completion, an average of 1 year.
Title
Epidemiological features 4
Description
Ethnicity (questionnaire [% of patients])
Time Frame
Through study completion, an average of 1 year.
Title
Epidemiological features 5
Description
Religion (questionnaire [% of patients] protestant, pentecostal or neopentecostal, spiritism, afro-brazilian, no religion or atheism and others]).
Time Frame
Through study completion, an average of 1 year.
Title
Epidemiological features 6
Description
Occupation (questionnaire [% of patients])
Time Frame
Through study completion, an average of 1 year.
Title
Epidemiological features 7
Description
Education (questionnaire [years])
Time Frame
Through study completion, an average of 1 year.
Title
Epidemiological features 8
Description
Individual income (questionnaire [dollars]).
Time Frame
Through study completion, an average of 1 year.
Title
Epidemiological features 9
Description
Family income (questionnaire [dollars]).
Time Frame
Through study completion, an average of 1 year.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of TRD, according to clinical evaluation and confirmed by SCID-IV (Structured Clinical Interview for the DSM);
Moderate to severe intensity of the disease;
Female patients in fertile conditions should be using a clinically accepted contraceptive method (oral contraceptive and/or condom);
a. Blood test will be requested at the diagnostic stage and in case of clinical doubt as to the patient's gestational status,
Literate and able to understand the tasks requested;
With clinical comorbidities, however compensated;
Patients and/or legal representatives should understand the nature of the study and sign the Informed Consent Form.
Exclusion Criteria:
Imminent risk of suicide;
Patients with psychoactive substance dependence;
Intellectual deficit and psychotic symptoms;
Bipolar spectrum disorders and other primary psychiatric diagnoses;
Allergic to ketamine;
Glaucoma;
Treatment with reversible MAOI (monoamine oxidase inhibitor) in the week prior to visit 0;
Treatment with irreversible MAOI in two weeks prior to visit 0;
Fluoxetine treatment within 4 weeks prior to visit 0;
Treatment with others antidepressants;
Treatment with antipsychotics, lithium, benzodiazepines or other psychotropic drugs within 7 days prior to visit 0;
a. Lorazepam and zolpidem may be used;
Patients who become pregnant will be excluded from the study and referred for obstetric care.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ricardo A Moreno, MD, PhD
Organizational Affiliation
Department and Institute of Psychiatry, University of Sao Paulo
Official's Role
Principal Investigator
Facility Information:
Facility Name
Núcleo de Pesquisas em Saúde Mental
City
Blumenau
State/Province
Santa Catarina
ZIP/Postal Code
89.020-070
Country
Brazil
12. IPD Sharing Statement
Plan to Share IPD
No
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Intramuscular Ketamine Versus Aripiprazole and Escitalopram in the Treatment of Resistant Depression
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