Trial Outcomes & Findings for Study to Treat Major Depressive Disorder With a New Medication (NCT NCT03043560)
NCT ID: NCT03043560
Last Updated: 2020-10-23
Results Overview
change in activation during reward anticipation within the bilateral VS from baseline (Study Visit 0) to the primary outcome visit (Study Visit 5) as measured by functional MRI during the incentive flanker task (IFT). The IFT, like the Monetary Incentive Delay task, permits discrete modeling of brain activity during anticipation of an incentive. Functional scans were preprocessed and denoised for motion and physiological noise using multi-echo independent component analysis (ME-ICA). Task-based modeling was conducted using AFNI and FSL software. The primary outcome for reward anticipation was the contrast of reward cue compared to neutral cue (reward\>neutral cue). The primary imaging outcome was analyzed using a linear mixed model with a single random intercept term treating time as discrete or continuous as appropriate.
COMPLETED
PHASE2
45 participants
baseline and 5 weeks
2020-10-23
Participant Flow
Participants recruited from Sept 2017 through August 2019
Participant milestones
| Measure |
Ezogabine
Ezogabine up to 900mg/day daily for 5 weeks
|
Placebo
Matching placebo pill daily for 5 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
21
|
24
|
|
Overall Study
COMPLETED
|
20
|
21
|
|
Overall Study
NOT COMPLETED
|
1
|
3
|
Reasons for withdrawal
| Measure |
Ezogabine
Ezogabine up to 900mg/day daily for 5 weeks
|
Placebo
Matching placebo pill daily for 5 weeks
|
|---|---|---|
|
Overall Study
Discontinued Intervention
|
1
|
2
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
Baseline Characteristics
Study to Treat Major Depressive Disorder With a New Medication
Baseline characteristics by cohort
| Measure |
Ezogabine
n=21 Participants
Ezogabine up to 900mg/day daily for 5 weeks
|
Placebo
n=24 Participants
Matching placebo pill daily for 5 weeks
|
Total
n=45 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
44.4 years
STANDARD_DEVIATION 13.6 • n=5 Participants
|
38.9 years
STANDARD_DEVIATION 14.3 • n=7 Participants
|
41.5 years
STANDARD_DEVIATION 14.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White/Caucasian
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic/Latino
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Employment at least Part-Time
|
9 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Educational Attainment - ast least some college
|
15 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
Relationship Status - Single, Never Married
|
8 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Primary Diagnosis
Major Depressive Disorder
|
21 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Primary Diagnosis
Persistent Depressive Disorder
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Current Major Depressive Episode
|
21 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
|
Age at Onset of Depression
|
28.3 years
STANDARD_DEVIATION 15.6 • n=5 Participants
|
21.7 years
STANDARD_DEVIATION 11.5 • n=7 Participants
|
24.3 years
STANDARD_DEVIATION 14.0 • n=5 Participants
|
|
Current Depressive Episode Duration
|
72 months
n=5 Participants
|
24 months
n=7 Participants
|
30 months
n=5 Participants
|
|
Generalized Anxiety Disorder
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Posttraumatic Stress Disorder (PTSD)
|
4 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: baseline and 5 weekschange in activation during reward anticipation within the bilateral VS from baseline (Study Visit 0) to the primary outcome visit (Study Visit 5) as measured by functional MRI during the incentive flanker task (IFT). The IFT, like the Monetary Incentive Delay task, permits discrete modeling of brain activity during anticipation of an incentive. Functional scans were preprocessed and denoised for motion and physiological noise using multi-echo independent component analysis (ME-ICA). Task-based modeling was conducted using AFNI and FSL software. The primary outcome for reward anticipation was the contrast of reward cue compared to neutral cue (reward\>neutral cue). The primary imaging outcome was analyzed using a linear mixed model with a single random intercept term treating time as discrete or continuous as appropriate.
Outcome measures
| Measure |
Ezogabine
n=21 Participants
Ezogabine up to 900mg/day daily for 5 weeks
|
Placebo
n=24 Participants
Matching placebo pill daily for 5 weeks
|
|---|---|---|
|
Change in Ventral Striatum (VS) Activation
baseline
|
-0.26 Bold Oxygen-level Dependent (BOLD) Signa
Standard Deviation 0.69
|
0.95 Bold Oxygen-level Dependent (BOLD) Signa
Standard Deviation 0.79
|
|
Change in Ventral Striatum (VS) Activation
5 weeks
|
0.176 Bold Oxygen-level Dependent (BOLD) Signa
Standard Deviation 0.81
|
0.015 Bold Oxygen-level Dependent (BOLD) Signa
Standard Deviation 0.68
|
SECONDARY outcome
Timeframe: baseline and 5 weeksThe SHAPS is a well-validated 14-item self-report questionnaire commonly used to assess anhedonia. Each item on the SHAPS is worded so that higher scores indicate greater pleasure capacity. A total score can be derived by summing the responses to each item. Items answered with "strongly agree" are coded as "1", while a "strongly disagree" response was assigned a score of "4." Total scores on the SHAPS can range from 14 to 56, with higher scores corresponding to higher levels of anhedonia.
Outcome measures
| Measure |
Ezogabine
n=21 Participants
Ezogabine up to 900mg/day daily for 5 weeks
|
Placebo
n=24 Participants
Matching placebo pill daily for 5 weeks
|
|---|---|---|
|
Change in Snaith-Hamilton Pleasure Scale (SHAPS)
Baseline
|
38.7 score on a scale
Standard Deviation 8.1
|
33.7 score on a scale
Standard Deviation 6
|
|
Change in Snaith-Hamilton Pleasure Scale (SHAPS)
5 weeks
|
27.5 score on a scale
Standard Deviation 8.5
|
30 score on a scale
Standard Deviation 10.9
|
SECONDARY outcome
Timeframe: baseline and 5 weeksA widely administered clinician rated global measure of the degree of improvement from the initial assessment in subject overall illness severity. 7 point scale rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Outcome measures
| Measure |
Ezogabine
n=21 Participants
Ezogabine up to 900mg/day daily for 5 weeks
|
Placebo
n=24 Participants
Matching placebo pill daily for 5 weeks
|
|---|---|---|
|
Clinical Global Impression - Improvement (CGI-I)
baseline
|
4 score on a scale
Standard Deviation 0.2
|
4 score on a scale
Standard Deviation 0.4
|
|
Clinical Global Impression - Improvement (CGI-I)
5 weeks
|
2.1 score on a scale
Standard Deviation 1
|
2.8 score on a scale
Standard Deviation 1.3
|
SECONDARY outcome
Timeframe: baseline and 5 weeksClinician rated global measure of subject overall illness severity. a 7-point scale rated as 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
Outcome measures
| Measure |
Ezogabine
n=21 Participants
Ezogabine up to 900mg/day daily for 5 weeks
|
Placebo
n=24 Participants
Matching placebo pill daily for 5 weeks
|
|---|---|---|
|
Clinical Global Impression - Severity (CGI-S)
baseline
|
4.4 score on a scale
Standard Deviation 0.5
|
4.6 score on a scale
Standard Deviation 0.6
|
|
Clinical Global Impression - Severity (CGI-S)
5 weeks
|
2.6 score on a scale
Standard Deviation 1.2
|
3.3 score on a scale
Standard Deviation 1.2
|
SECONDARY outcome
Timeframe: baseline and 5 weeksA measure specifically designed to assess hedonic capacity for social and interpersonal pleasure.The ACIPS is a 17-item self-report measure scored on a likert scale, ranging from 1 (very false for me) to 6 (very true for me). Full scale from 17-102, higher score indicates higher hedonic capacity
Outcome measures
| Measure |
Ezogabine
n=21 Participants
Ezogabine up to 900mg/day daily for 5 weeks
|
Placebo
n=24 Participants
Matching placebo pill daily for 5 weeks
|
|---|---|---|
|
Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS)
baseline
|
46.1 score on a scale
Standard Deviation 15.1
|
53.7 score on a scale
Standard Deviation 15
|
|
Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS)
5 weeks
|
65.1 score on a scale
Standard Deviation 22.8
|
59 score on a scale
Standard Deviation 23.5
|
SECONDARY outcome
Timeframe: baseline and 5 weeksA 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each items is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression).
Outcome measures
| Measure |
Ezogabine
n=21 Participants
Ezogabine up to 900mg/day daily for 5 weeks
|
Placebo
n=24 Participants
Matching placebo pill daily for 5 weeks
|
|---|---|---|
|
Montgomery-Asberg Depression Rating Scale (MADRS)
baseline
|
28.3 score on a scale
Standard Deviation 6.1
|
26.8 score on a scale
Standard Deviation 5.1
|
|
Montgomery-Asberg Depression Rating Scale (MADRS)
5 weeks
|
12.7 score on a scale
Standard Deviation 8.7
|
18.5 score on a scale
Standard Deviation 10.1
|
SECONDARY outcome
Timeframe: baseline and 5 weeksA 12-item generic assessment instrument that measures the level of functioning. Each item is scored from 0 to 4 and the items are summed to provide a total score. The score therefore ranges from 0 to 48, with higher scores indicating greater disability.
Outcome measures
| Measure |
Ezogabine
n=21 Participants
Ezogabine up to 900mg/day daily for 5 weeks
|
Placebo
n=24 Participants
Matching placebo pill daily for 5 weeks
|
|---|---|---|
|
World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)
baseline
|
15.5 score on a scale
Standard Deviation 7.5
|
16.5 score on a scale
Standard Deviation 9.4
|
|
World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)
5 weeks
|
10.2 score on a scale
Standard Deviation 9.5
|
11.6 score on a scale
Standard Deviation 9.8
|
SECONDARY outcome
Timeframe: baseline and 5 weeksThe TEPS is composed of 18-items rated on a likert-type scale ranging from 1 (Very True for me) to 6 (Very False for me), and yields two subscales. Ten items make up the TEPS-Anticipatory Pleasure (TEPS-ANT) scale with a range from 10 (not motivated) to 60 (highly motivated). The other eight TEPS items make up the TEPS-Consummatory Pleasure (TEPS-CON) scale; range from 8 (not responsive) to 48 (highly responsive). Total scores range is 18-108. Lower scores indicate greater levels of anhedonia.
Outcome measures
| Measure |
Ezogabine
n=21 Participants
Ezogabine up to 900mg/day daily for 5 weeks
|
Placebo
n=24 Participants
Matching placebo pill daily for 5 weeks
|
|---|---|---|
|
Temporal Experience of Pleasure Scale (TEPS)
TEPS-ANT baseline
|
26.3 score on a scale
Standard Deviation 8.3
|
28.6 score on a scale
Standard Deviation 8.7
|
|
Temporal Experience of Pleasure Scale (TEPS)
TEPS-ANT 5 weeks
|
37.3 score on a scale
Standard Deviation 10.5
|
32.4 score on a scale
Standard Deviation 11.5
|
|
Temporal Experience of Pleasure Scale (TEPS)
TEPS-CON baseline
|
24.8 score on a scale
Standard Deviation 8.1
|
25.6 score on a scale
Standard Deviation 7.6
|
|
Temporal Experience of Pleasure Scale (TEPS)
TEPS-CON 5 weeks
|
32.2 score on a scale
Standard Deviation 6
|
29.9 score on a scale
Standard Deviation 10.5
|
SECONDARY outcome
Timeframe: baseline 5 weeksThe SLIPS is a recently developed and validated measure of anhedonia that is tailored to detect recent changes in anhedonia. A 23-item measure, each item range from 0-3. Full scale from 0 to 69, higher score indicates more recent changes.
Outcome measures
| Measure |
Ezogabine
n=21 Participants
Ezogabine up to 900mg/day daily for 5 weeks
|
Placebo
n=24 Participants
Matching placebo pill daily for 5 weeks
|
|---|---|---|
|
Specific Loss of Interest and Pleasure Scale (SLIPS)
baseline
|
32.3 score on a scale
Standard Deviation 9.8
|
28.8 score on a scale
Standard Deviation 10.4
|
|
Specific Loss of Interest and Pleasure Scale (SLIPS)
5 weeks
|
16.3 score on a scale
Standard Deviation 16.7
|
21.5 score on a scale
Standard Deviation 16.8
|
Adverse Events
Ezogabine
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Ezogabine
n=21 participants at risk
Ezogabine up to 900mg/day daily for 5 weeks
|
Placebo
n=24 participants at risk
Matching placebo pill daily for 5 weeks
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
9.5%
2/21 • 8 weeks
|
12.5%
3/24 • 8 weeks
|
|
Psychiatric disorders
Anxiety
|
4.8%
1/21 • 8 weeks
|
4.2%
1/24 • 8 weeks
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/21 • 8 weeks
|
4.2%
1/24 • 8 weeks
|
|
Psychiatric disorders
Confusional state
|
19.0%
4/21 • 8 weeks
|
0.00%
0/24 • 8 weeks
|
|
Gastrointestinal disorders
Constipation
|
4.8%
1/21 • 8 weeks
|
8.3%
2/24 • 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.8%
1/21 • 8 weeks
|
4.2%
1/24 • 8 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
23.8%
5/21 • 8 weeks
|
4.2%
1/24 • 8 weeks
|
|
Nervous system disorders
Disturbance in attention
|
14.3%
3/21 • 8 weeks
|
0.00%
0/24 • 8 weeks
|
|
Nervous system disorders
Dizziness
|
100.0%
21/21 • 8 weeks
|
20.8%
5/24 • 8 weeks
|
|
Gastrointestinal disorders
Dry mouth
|
4.8%
1/21 • 8 weeks
|
0.00%
0/24 • 8 weeks
|
|
Nervous system disorders
Headache
|
23.8%
5/21 • 8 weeks
|
29.2%
7/24 • 8 weeks
|
|
Metabolism and nutrition disorders
Increased appetite
|
4.8%
1/21 • 8 weeks
|
0.00%
0/24 • 8 weeks
|
|
General disorders
Malaise
|
4.8%
1/21 • 8 weeks
|
0.00%
0/24 • 8 weeks
|
|
Nervous system disorders
Memory impairment
|
4.8%
1/21 • 8 weeks
|
8.3%
2/24 • 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
4.8%
1/21 • 8 weeks
|
0.00%
0/24 • 8 weeks
|
|
Gastrointestinal disorders
Nausea
|
14.3%
3/21 • 8 weeks
|
20.8%
5/24 • 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
4.8%
1/21 • 8 weeks
|
0.00%
0/24 • 8 weeks
|
|
Cardiac disorders
Palpitations
|
4.8%
1/21 • 8 weeks
|
4.2%
1/24 • 8 weeks
|
|
Psychiatric disorders
Panic attack
|
9.5%
2/21 • 8 weeks
|
0.00%
0/24 • 8 weeks
|
|
Renal and urinary disorders
Polyuria
|
0.00%
0/21 • 8 weeks
|
4.2%
1/24 • 8 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
9.5%
2/21 • 8 weeks
|
0.00%
0/24 • 8 weeks
|
|
Psychiatric disorders
Restlessness
|
0.00%
0/21 • 8 weeks
|
4.2%
1/24 • 8 weeks
|
|
Nervous system disorders
Sedation
|
0.00%
0/21 • 8 weeks
|
4.2%
1/24 • 8 weeks
|
|
Nervous system disorders
Somnolence
|
9.5%
2/21 • 8 weeks
|
12.5%
3/24 • 8 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/21 • 8 weeks
|
4.2%
1/24 • 8 weeks
|
|
Eye disorders
Vision blurred
|
14.3%
3/21 • 8 weeks
|
4.2%
1/24 • 8 weeks
|
|
Gastrointestinal disorders
Vomiting
|
9.5%
2/21 • 8 weeks
|
4.2%
1/24 • 8 weeks
|
|
General disorders
Other
|
42.9%
9/21 • 8 weeks
|
33.3%
8/24 • 8 weeks
|
Additional Information
Dr, James Murrough
Icahn School of Medicine at Mount Sinai
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place