Trial Outcomes & Findings for Ketamine for Treatment Resistant Late-Life Depression (NCT NCT02556606)
NCT ID: NCT02556606
Last Updated: 2022-01-11
Results Overview
To determine the best performing intervention among three sub-anesthetic doses of a single ketamine (0.1 mg/kg, 0.25 mg/kg, and 0.50 mg/kg) and midazolam (0.03 mg/kg) in Veterans with LL-TRD as measured by the percentage of participants demonstrating at least a 50% reduction from pre-treatment baseline on Montgomery-Asberg Depression Rating Scale (MADRS; score range 0 - 60, higher scores meaning more severe depression) scores at 7 days post-infusion.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
33 participants
Primary outcome timeframe
Day 7 post-infusion
Results posted on
2022-01-11
Participant Flow
Participant milestones
| Measure |
Ketamine 0.10 mg/kg
randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
|
Ketamine 0.25 mg/kg
randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
|
Ketamine 0.50 mg/kg
randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
|
Midazolam 0.03 mg/kg
randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg
Midazolam: single 40 min infusion of MID 0.03mg/Kg
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
5
|
11
|
13
|
|
Overall Study
COMPLETED
|
4
|
5
|
11
|
13
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Ketamine for Treatment Resistant Late-Life Depression
Baseline characteristics by cohort
| Measure |
Ketamine 0.10 mg/kg
n=4 Participants
randomly assigned to a single 40 min infusion of KET 0.1 mg/kg
|
Ketamine 0.25 mg/kg
n=5 Participants
randomly assigned to a single 40 min infusion of KET 0.25 mg/kg
|
Ketamine 0.50 mg/kg
n=11 Participants
randomly assigned to a single 40 min infusion of KET 0.50 mg/kg
|
Midazolam 0.03 mg/kg
n=13 Participants
randomly assigned to a single 40 min infusion of MID 0.03 mg/kg
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
66.75 Years
STANDARD_DEVIATION 5.54 • n=5 Participants
|
61.8 Years
STANDARD_DEVIATION 6.06 • n=7 Participants
|
60.91 Years
STANDARD_DEVIATION 4.97 • n=5 Participants
|
62.15 Years
STANDARD_DEVIATION 5.54 • n=4 Participants
|
62.24 Years
STANDARD_DEVIATION 5.60 • n=21 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
23 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
31 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 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
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
17 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Day 7 post-infusionTo determine the best performing intervention among three sub-anesthetic doses of a single ketamine (0.1 mg/kg, 0.25 mg/kg, and 0.50 mg/kg) and midazolam (0.03 mg/kg) in Veterans with LL-TRD as measured by the percentage of participants demonstrating at least a 50% reduction from pre-treatment baseline on Montgomery-Asberg Depression Rating Scale (MADRS; score range 0 - 60, higher scores meaning more severe depression) scores at 7 days post-infusion.
Outcome measures
| Measure |
Ketamine 0.10 mg/kg
n=4 Participants
randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
|
Ketamine 0.25 mg/kg
n=5 Participants
randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
|
Ketamine 0.50 mg/kg
n=11 Participants
randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
|
Midazolam 0.03 mg/kg
n=13 Participants
randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg
Midazolam: single 40 min infusion of MID 0.03mg/Kg
|
|---|---|---|---|---|
|
Percentage of Participants Demonstrating at Least a 50% Reduction on Montgomery-Asberg Depression Rating Scale Scores
|
0 Participants
|
2 Participants
|
8 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: 28 days post-infusion follow-upPopulation: Day 7 responders were followed until day 28 post-infusion or until relapse
Patients with a day 7 treatment response (at least a 50% improvement from baseline in Montgomery-Asberg Depression Rating Scale \[MADRS\]) are followed until day 28 post-infusion; day 7 non-responders are not followed. Outcome measure is the percentage of patients who continue to be responder at day 28, and is interpreted as a measure of durability of efficacy.
Outcome measures
| Measure |
Ketamine 0.10 mg/kg
randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
|
Ketamine 0.25 mg/kg
n=2 Participants
randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
|
Ketamine 0.50 mg/kg
n=8 Participants
randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
|
Midazolam 0.03 mg/kg
n=6 Participants
randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg
Midazolam: single 40 min infusion of MID 0.03mg/Kg
|
|---|---|---|---|---|
|
Percentage of Patients With Continuation From Day 7 to Day 28 Post-infusion of at Least a 50% Improvement in MADRS
|
0 Participants
|
1 Participants
|
7 Participants
|
4 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 40 minutes after start of infusionChange from pre-infusion baseline to end of infusion at 40 minutes after start of infusion on the Clinician-Administered Dissociative States Scale (CADSS; scale form 0 \[no psychosis-like symptoms\] to 90 \[severe psychosis-like symptoms\]) to assess psychosis-like side effect on day of infusion.
Outcome measures
| Measure |
Ketamine 0.10 mg/kg
n=4 Participants
randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
|
Ketamine 0.25 mg/kg
n=5 Participants
randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
|
Ketamine 0.50 mg/kg
n=11 Participants
randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
|
Midazolam 0.03 mg/kg
n=13 Participants
randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg
Midazolam: single 40 min infusion of MID 0.03mg/Kg
|
|---|---|---|---|---|
|
Change in Clinician-Administered Dissociative States Scale (CADSS)
Pre-infusion baseline
|
1.41 Score on CADSS scale
Standard Deviation 0.71
|
0 Score on CADSS scale
Standard Deviation 0
|
0.09 Score on CADSS scale
Standard Deviation 0.30
|
0.23 Score on CADSS scale
Standard Deviation 0.60
|
|
Change in Clinician-Administered Dissociative States Scale (CADSS)
End of infusion at 40 minutes
|
4.79 Score on CADSS scale
Standard Deviation 2.39
|
14.98 Score on CADSS scale
Standard Deviation 6.70
|
21.36 Score on CADSS scale
Standard Deviation 20.53
|
4.38 Score on CADSS scale
Standard Deviation 6.73
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 30 minutes after start of infusionPopulation: Missing data due to poor data quality for KET 0.1 (n=1), KET 0.5 (n=3) or MID (n=3)
Change in EEG frontal gamma power from pre-infusion baseline to 30 minutes after start of infusion to assess engagement of the study drug with the N-methyl-D-aspartate receptor.
Outcome measures
| Measure |
Ketamine 0.10 mg/kg
n=3 Participants
randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
|
Ketamine 0.25 mg/kg
n=5 Participants
randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
|
Ketamine 0.50 mg/kg
n=8 Participants
randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
|
Midazolam 0.03 mg/kg
n=10 Participants
randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg
Midazolam: single 40 min infusion of MID 0.03mg/Kg
|
|---|---|---|---|---|
|
Change in Resting-state Quantitative Electroencephalography (EEG) Frontal Gamma Band Power (Log of Microvolt Squared)
Pre-infusion baseline
|
0.0019 uV^2
Standard Deviation 0.0004
|
0.055 uV^2
Standard Deviation 0.0030
|
0.0042 uV^2
Standard Deviation 0.0026
|
0.0061 uV^2
Standard Deviation 0.0078
|
|
Change in Resting-state Quantitative Electroencephalography (EEG) Frontal Gamma Band Power (Log of Microvolt Squared)
30 minutes after start of infusion
|
0.0035 uV^2
Standard Deviation 0.0012
|
0.0057 uV^2
Standard Deviation 0.0044
|
0.0098 uV^2
Standard Deviation 0.0067
|
0.004 uV^2
Standard Deviation 0.0027
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 30 minutes after start of infusionChange in systolic blood pressure from pre-infusion baseline to 30 minutes after start of infusion
Outcome measures
| Measure |
Ketamine 0.10 mg/kg
n=4 Participants
randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
|
Ketamine 0.25 mg/kg
n=5 Participants
randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
|
Ketamine 0.50 mg/kg
n=11 Participants
randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
|
Midazolam 0.03 mg/kg
n=13 Participants
randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg
Midazolam: single 40 min infusion of MID 0.03mg/Kg
|
|---|---|---|---|---|
|
Change in Systolic Blood Pressure (Millimeters of Mercury, mm Hg)
Pre-infusion baseline
|
154.25 mm Hg
Standard Deviation 5.91
|
142.2 mm Hg
Standard Deviation 15.97
|
132.91 mm Hg
Standard Deviation 10.56
|
125.54 mm Hg
Standard Deviation 213.01
|
|
Change in Systolic Blood Pressure (Millimeters of Mercury, mm Hg)
30 minutes after start of infusion
|
152.75 mm Hg
Standard Deviation 12.97
|
148.2 mm Hg
Standard Deviation 18.07
|
160.36 mm Hg
Standard Deviation 25.94
|
116.62 mm Hg
Standard Deviation 15.56
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 30 minutes after start of infusionChange in systolic blood pressure from pre-infusion baseline to 30 minutes after start of infusion
Outcome measures
| Measure |
Ketamine 0.10 mg/kg
n=4 Participants
randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
|
Ketamine 0.25 mg/kg
n=5 Participants
randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
|
Ketamine 0.50 mg/kg
n=11 Participants
randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
|
Midazolam 0.03 mg/kg
n=13 Participants
randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg
Midazolam: single 40 min infusion of MID 0.03mg/Kg
|
|---|---|---|---|---|
|
Change in Diastolic Blood Pressure (Millimeters of Mercury, mm Hg)
Pre-infusion baseline
|
80.5 mm Hg
Standard Deviation 7.05
|
74.6 mm Hg
Standard Deviation 13.37
|
82.64 mm Hg
Standard Deviation 4.72
|
72.23 mm Hg
Standard Deviation 9.36
|
|
Change in Diastolic Blood Pressure (Millimeters of Mercury, mm Hg)
30 minutes after start of infusion
|
91.25 mm Hg
Standard Deviation 14.24
|
82.6 mm Hg
Standard Deviation 18.53
|
95.45 mm Hg
Standard Deviation 16.01
|
73.54 mm Hg
Standard Deviation 12.29
|
Adverse Events
Ketamine 0.10 mg/kg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Ketamine 0.25 mg/kg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Ketamine 0.50 mg/kg
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Midazolam 0.03 mg/kg
Serious events: 1 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ketamine 0.10 mg/kg
n=4 participants at risk
randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
|
Ketamine 0.25 mg/kg
n=5 participants at risk
randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
|
Ketamine 0.50 mg/kg
n=11 participants at risk
randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
|
Midazolam 0.03 mg/kg
n=13 participants at risk
randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg
Midazolam: single 40 min infusion of MID 0.03mg/Kg
|
|---|---|---|---|---|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/4 • 28 days
|
0.00%
0/5 • 28 days
|
0.00%
0/11 • 28 days
|
7.7%
1/13 • Number of events 1 • 28 days
|
Other adverse events
| Measure |
Ketamine 0.10 mg/kg
n=4 participants at risk
randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
|
Ketamine 0.25 mg/kg
n=5 participants at risk
randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
|
Ketamine 0.50 mg/kg
n=11 participants at risk
randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
Ketamine: randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
|
Midazolam 0.03 mg/kg
n=13 participants at risk
randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg
Midazolam: single 40 min infusion of MID 0.03mg/Kg
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal complaints
|
100.0%
4/4 • Number of events 4 • 28 days
|
80.0%
4/5 • Number of events 4 • 28 days
|
72.7%
8/11 • Number of events 8 • 28 days
|
84.6%
11/13 • Number of events 11 • 28 days
|
|
Cardiac disorders
Cardiac complaints
|
25.0%
1/4 • Number of events 1 • 28 days
|
60.0%
3/5 • Number of events 3 • 28 days
|
36.4%
4/11 • Number of events 4 • 28 days
|
53.8%
7/13 • Number of events 7 • 28 days
|
|
Skin and subcutaneous tissue disorders
Skin complaints
|
100.0%
4/4 • Number of events 4 • 28 days
|
100.0%
5/5 • Number of events 5 • 28 days
|
63.6%
7/11 • Number of events 7 • 28 days
|
69.2%
9/13 • Number of events 9 • 28 days
|
|
Nervous system disorders
Nervous system complaints
|
100.0%
4/4 • Number of events 4 • 28 days
|
100.0%
5/5 • Number of events 5 • 28 days
|
63.6%
7/11 • Number of events 7 • 28 days
|
84.6%
11/13 • Number of events 11 • 28 days
|
|
Eye disorders
Eye or ear complaints
|
75.0%
3/4 • Number of events 3 • 28 days
|
100.0%
5/5 • Number of events 5 • 28 days
|
36.4%
4/11 • Number of events 4 • 28 days
|
84.6%
11/13 • Number of events 11 • 28 days
|
|
Reproductive system and breast disorders
Genital or urinary complaints
|
50.0%
2/4 • Number of events 2 • 28 days
|
60.0%
3/5 • Number of events 3 • 28 days
|
45.5%
5/11 • Number of events 5 • 28 days
|
46.2%
6/13 • Number of events 6 • 28 days
|
|
General disorders
Sleep complaints
|
100.0%
4/4 • Number of events 4 • 28 days
|
100.0%
5/5 • Number of events 5 • 28 days
|
100.0%
11/11 • Number of events 11 • 28 days
|
100.0%
13/13 • Number of events 13 • 28 days
|
|
Reproductive system and breast disorders
Sexual functioning complaints
|
75.0%
3/4 • Number of events 3 • 28 days
|
80.0%
4/5 • Number of events 4 • 28 days
|
81.8%
9/11 • Number of events 9 • 28 days
|
92.3%
12/13 • Number of events 12 • 28 days
|
|
General disorders
Other complaints
|
100.0%
4/4 • Number of events 4 • 28 days
|
100.0%
5/5 • Number of events 5 • 28 days
|
100.0%
11/11 • Number of events 11 • 28 days
|
100.0%
13/13 • Number of events 13 • 28 days
|
Additional Information
Marijn Lijffijt, PhD
Michael E. DeBakey VA Medical Center
Phone: 3618274395
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place