Trial Outcomes & Findings for Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects (NCT NCT02487485)
NCT ID: NCT02487485
Last Updated: 2020-07-16
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
23 participants
Primary outcome timeframe
Pretreatment and 2 week
Results posted on
2020-07-16
Participant Flow
Participant milestones
| Measure |
Ketamine + Sirolimus First, Then Ketamine + Placebo
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.
|
Ketamine + Placebo First, Then Ketamine + Sirolimus
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.
|
|---|---|---|
|
Overall Study
STARTED
|
12
|
11
|
|
Overall Study
COMPLETED
|
9
|
8
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects
Baseline characteristics by cohort
| Measure |
Ketamine + Sirolimus First, Then Ketamine + Placebo
n=11 Participants
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.
|
Ketamine + Placebo First, Then Ketamine + Sirolimus
n=10 Participants
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
n=21 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
40.09 years
STANDARD_DEVIATION 13.22 • n=5 Participants
|
44.1 years
STANDARD_DEVIATION 12.6 • n=7 Participants
|
42 years
STANDARD_DEVIATION 12.79 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pretreatment and 2 weekMontgomery-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).
Outcome measures
| Measure |
Ketamine + Sirolimus
n=20 Participants
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally.
|
Ketamine + Placebo
n=20 Participants
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
|
|---|---|---|
|
Montgomery-Asberg Depression Rating Scale
Pretreatment
|
27.9387 score on a scale
Standard Error 1.9
|
26.5756 score on a scale
Standard Error 1.9
|
|
Montgomery-Asberg Depression Rating Scale
At 2 weeks
|
16.5482 score on a scale
Standard Error 2.3
|
20.9065 score on a scale
Standard Error 2.3
|
SECONDARY outcome
Timeframe: Pretreatment and 2 weekQuick Inventory of Depressive Symptoms - Self-Report (QIDS-SR): The QIDS-SR is a patient-rated depression instrument. Ranges from 0-27 (higher is worse).
Outcome measures
| Measure |
Ketamine + Sirolimus
n=20 Participants
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally.
|
Ketamine + Placebo
n=20 Participants
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
|
|---|---|---|
|
Quick Inventory of Depressive Symptoms (QIDS)
Pretreatment
|
12.6342 score on a scale
Standard Error 1.4
|
11.3942 score on a scale
Standard Error 1.4
|
|
Quick Inventory of Depressive Symptoms (QIDS)
At 2 weeks
|
9.1193 score on a scale
Standard Error 1.2
|
10.6699 score on a scale
Standard Error 1.3
|
SECONDARY outcome
Timeframe: Pretreatment and 2 weekHamilton 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).
Outcome measures
| Measure |
Ketamine + Sirolimus
n=20 Participants
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally.
|
Ketamine + Placebo
n=20 Participants
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
|
|---|---|---|
|
Hamilton Anxiety Rating Scale (HAMA)
Pretreatment
|
12.9678 score on a scale
Standard Error 1.4
|
13.8222 score on a scale
Standard Error 1.4
|
|
Hamilton Anxiety Rating Scale (HAMA)
At 2 weeks
|
9.8755 score on a scale
Standard Error 1.4
|
10.8669 score on a scale
Standard Error 1.6
|
SECONDARY outcome
Timeframe: During infusion, approximately 40 minsClinician 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).
Outcome measures
| Measure |
Ketamine + Sirolimus
n=20 Participants
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally.
|
Ketamine + Placebo
n=20 Participants
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
|
|---|---|---|
|
Clinician Administered Dissociative States Scale (CADSS)
|
12.1 score on a scale
Standard Error 3.1
|
13.95 score on a scale
Standard Error 3.1
|
SECONDARY outcome
Timeframe: During infusion, approximately 40 minsPositive 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).
Outcome measures
| Measure |
Ketamine + Sirolimus
n=20 Participants
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally.
|
Ketamine + Placebo
n=20 Participants
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
|
|---|---|---|
|
Positive and Negative Symptom Scale (PANSS) - Positive
|
9.1537 score on a scale
Standard Error 0.59
|
8.9444 score on a scale
Standard Error 0.60
|
SECONDARY outcome
Timeframe: During infusion, approximately 0 minsPlasma level of rapamycin (a.k.a. sirolimus).
Outcome measures
| Measure |
Ketamine + Sirolimus
n=20 Participants
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally.
|
Ketamine + Placebo
n=20 Participants
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
|
|---|---|---|
|
Rapamycin Level
|
26.5 ng/mL
Standard Error 2.4
|
0 ng/mL
Standard Error 0
|
SECONDARY outcome
Timeframe: During infusion, approximately 40 minsPlasma level of ketamine
Outcome measures
| Measure |
Ketamine + Sirolimus
n=20 Participants
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally.
|
Ketamine + Placebo
n=20 Participants
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
|
|---|---|---|
|
Ketamine Level
|
115 ng/mL
Standard Error 16
|
125 ng/mL
Standard Error 13
|
Adverse Events
Ketamine + Sirolimus
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Ketamine + Placebo
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Ketamine + Sirolimus
n=20 participants at risk
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally.
|
Ketamine + Placebo
n=20 participants at risk
Participants received ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of placebo.
|
|---|---|---|
|
Psychiatric disorders
Anxiety
|
5.0%
1/20 • 4 weeks
|
0.00%
0/20 • 4 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Chest Tightness
|
5.0%
1/20 • 4 weeks
|
0.00%
0/20 • 4 weeks
|
|
Psychiatric disorders
Depression
|
5.0%
1/20 • 4 weeks
|
5.0%
1/20 • 4 weeks
|
|
General disorders
Dizzy
|
10.0%
2/20 • 4 weeks
|
0.00%
0/20 • 4 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
5.0%
1/20 • 4 weeks
|
5.0%
1/20 • 4 weeks
|
|
General disorders
Dry Mouth
|
0.00%
0/20 • 4 weeks
|
5.0%
1/20 • 4 weeks
|
|
General disorders
Fatigue
|
20.0%
4/20 • 4 weeks
|
15.0%
3/20 • 4 weeks
|
|
General disorders
Fever
|
5.0%
1/20 • 4 weeks
|
0.00%
0/20 • 4 weeks
|
|
Gastrointestinal disorders
GI Discomfort
|
10.0%
2/20 • 4 weeks
|
0.00%
0/20 • 4 weeks
|
|
Nervous system disorders
Headaches
|
15.0%
3/20 • 4 weeks
|
15.0%
3/20 • 4 weeks
|
|
Gastrointestinal disorders
Nausea
|
15.0%
3/20 • 4 weeks
|
10.0%
2/20 • 4 weeks
|
|
General disorders
Pain
|
15.0%
3/20 • 4 weeks
|
5.0%
1/20 • 4 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Issues
|
10.0%
2/20 • 4 weeks
|
0.00%
0/20 • 4 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place