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Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects

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ClinicalTrials.gov Identifier: NCT02487485
Recruitment Status : Completed
First Posted : July 1, 2015
Results First Posted : July 7, 2020
Last Update Posted : July 16, 2020
Sponsor:
Information provided by (Responsible Party):
Yale University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Other
Condition Depression
Interventions Drug: Ketamine
Drug: sirolimus
Drug: Placebo
Enrollment 23
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ketamine + Sirolimus First, Then Ketamine + Placebo Ketamine + Placebo First, Then Ketamine + Sirolimus
Hide Arm/Group Description Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally. After two weeks, they received another infusion of ketamine, and a single dose of placebo. Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo. After two weeks, they received another infusion of ketamine, and a single dose of sirolimus 6 mg.
Period Title: Overall Study
Started 12 11
Completed 9 8
Not Completed 3 3
Arm/Group Title Ketamine + Sirolimus First, Then Ketamine + Placebo Ketamine + Placebo First, Then Ketamine + Sirolimus Total
Hide Arm/Group Description Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally. After two weeks, they received another infusion of ketamine, and a single dose of placebo. Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo. After two weeks, they received another infusion of ketamine, and a single dose of sirolimus 6 mg. Total of all reporting groups
Overall Number of Baseline Participants 11 10 21
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 11 participants 10 participants 21 participants
40.09  (13.22) 44.1  (12.6) 42  (12.79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 10 participants 21 participants
Female
6
  54.5%
8
  80.0%
14
  66.7%
Male
5
  45.5%
2
  20.0%
7
  33.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 10 participants 21 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   9.1%
1
  10.0%
2
   9.5%
White
10
  90.9%
6
  60.0%
16
  76.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
3
  30.0%
3
  14.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 11 participants 10 participants 21 participants
11
 100.0%
10
 100.0%
21
 100.0%
1.Primary Outcome
Title Montgomery-Asberg Depression Rating Scale
Hide Description Montgomery-Asberg Depression Rating Scale (MADRS): The MADRS is a standardized instrument to ascertain depressed mood and neurovegetative signs and symptoms of depression. Ranges from 0-60 (higher is worse).
Time Frame Pretreatment and 2 week
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine + Sirolimus Ketamine + Placebo
Hide Arm/Group Description:
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally.
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
Overall Number of Participants Analyzed 20 20
Mean (Standard Error)
Unit of Measure: score on a scale
Pretreatment 27.9387  (1.9) 26.5756  (1.9)
At 2 weeks 16.5482  (2.3) 20.9065  (2.3)
2.Secondary Outcome
Title Quick Inventory of Depressive Symptoms (QIDS)
Hide Description Quick Inventory of Depressive Symptoms - Self-Report (QIDS-SR): The QIDS-SR is a patient-rated depression instrument. Ranges from 0-27 (higher is worse).
Time Frame Pretreatment and 2 week
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine + Sirolimus Ketamine + Placebo
Hide Arm/Group Description:
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally.
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
Overall Number of Participants Analyzed 20 20
Mean (Standard Error)
Unit of Measure: score on a scale
Pretreatment 12.6342  (1.4) 11.3942  (1.4)
At 2 weeks 9.1193  (1.2) 10.6699  (1.3)
3.Secondary Outcome
Title Hamilton Anxiety Rating Scale (HAMA)
Hide Description Hamilton Anxiety Rating Scale (HAM-A): The HAM-A is a standardized clinician-rated instrument to evaluate the severity of anxiety symptoms. Ranges from 0-56 (higher is worse).
Time Frame Pretreatment and 2 week
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine + Sirolimus Ketamine + Placebo
Hide Arm/Group Description:
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally.
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
Overall Number of Participants Analyzed 20 20
Mean (Standard Error)
Unit of Measure: score on a scale
Pretreatment 12.9678  (1.4) 13.8222  (1.4)
At 2 weeks 9.8755  (1.4) 10.8669  (1.6)
4.Secondary Outcome
Title Clinician Administered Dissociative States Scale (CADSS)
Hide Description Clinician Administered Dissociative States Scale (CADSS): The CADSS has self and interviewer-administered items including 5 subscales, generated a priori, evaluating dissociation including altered environmental perception, time perception, spatial/body perception, derealization and memory impairment. Ranges from 0-108 (higher is worse).
Time Frame During infusion, approximately 40 mins
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine + Sirolimus Ketamine + Placebo
Hide Arm/Group Description:
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally.
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
Overall Number of Participants Analyzed 20 20
Mean (Standard Error)
Unit of Measure: score on a scale
12.1  (3.1) 13.95  (3.1)
5.Secondary Outcome
Title Positive and Negative Symptom Scale (PANSS) - Positive
Hide Description Positive and Negative Symptom Scale (PANSS): The PANSS is commonly used to measure the severity of symptoms in psychotic disorders. It is a clinician- administered scale and includes three categories of symptoms: (1) positive symptoms, such as hallucination and delusion; (2) negative symptoms, such as flat affect and difficulty in abstract thinking; (3) general psychopathology, such as mannerisms and posturing. Ranges from 0-49 for positive scale (higher is worse).
Time Frame During infusion, approximately 40 mins
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine + Sirolimus Ketamine + Placebo
Hide Arm/Group Description:
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally.
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
Overall Number of Participants Analyzed 20 20
Mean (Standard Error)
Unit of Measure: score on a scale
9.1537  (0.59) 8.9444  (0.60)
6.Secondary Outcome
Title Rapamycin Level
Hide Description Plasma level of rapamycin (a.k.a. sirolimus).
Time Frame During infusion, approximately 0 mins
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine + Sirolimus Ketamine + Placebo
Hide Arm/Group Description:
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally.
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
Overall Number of Participants Analyzed 20 20
Mean (Standard Error)
Unit of Measure: ng/mL
26.5  (2.4) 0  (0)
7.Secondary Outcome
Title Ketamine Level
Hide Description Plasma level of ketamine
Time Frame During infusion, approximately 40 mins
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine + Sirolimus Ketamine + Placebo
Hide Arm/Group Description:
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally.
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
Overall Number of Participants Analyzed 20 20
Mean (Standard Error)
Unit of Measure: ng/mL
115  (16) 125  (13)
Time Frame 4 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ketamine + Sirolimus Ketamine + Placebo
Hide Arm/Group Description Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally. Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
All-Cause Mortality
Ketamine + Sirolimus Ketamine + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/20 (0.00%)      0/20 (0.00%)    
Hide Serious Adverse Events
Ketamine + Sirolimus Ketamine + Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/20 (0.00%)      0/20 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Ketamine + Sirolimus Ketamine + Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/20 (30.00%)      6/20 (30.00%)    
Gastrointestinal disorders     
Diarrhea *  1/20 (5.00%)  1/20 (5.00%) 
GI Discomfort *  2/20 (10.00%)  0/20 (0.00%) 
Nausea *  3/20 (15.00%)  2/20 (10.00%) 
General disorders     
Dizzy *  2/20 (10.00%)  0/20 (0.00%) 
Dry Mouth *  0/20 (0.00%)  1/20 (5.00%) 
Fatigue *  4/20 (20.00%)  3/20 (15.00%) 
Fever *  1/20 (5.00%)  0/20 (0.00%) 
Pain *  3/20 (15.00%)  1/20 (5.00%) 
Nervous system disorders     
Headaches *  3/20 (15.00%)  3/20 (15.00%) 
Psychiatric disorders     
Anxiety *  1/20 (5.00%)  0/20 (0.00%)  0
Depression *  1/20 (5.00%)  1/20 (5.00%) 
Respiratory, thoracic and mediastinal disorders     
Chest Tightness *  1/20 (5.00%)  0/20 (0.00%) 
Upper Respiratory Issues *  2/20 (10.00%)  0/20 (0.00%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chadi Abdallah
Organization: Yale School of Medicine
Phone: 347-987-0717
EMail: chadi.abdallah@yale.edu
Layout table for additonal information
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02487485    
Other Study ID Numbers: 1504015604
First Submitted: June 29, 2015
First Posted: July 1, 2015
Results First Submitted: April 22, 2020
Results First Posted: July 7, 2020
Last Update Posted: July 16, 2020