Trial Outcomes & Findings for Neurosteroids as Novel Therapeutic Agents for Chronic Pain in OEF/OIF Veterans (NCT NCT01898013)
NCT ID: NCT01898013
Last Updated: 2018-10-03
Results Overview
Weekly mean of the 24-hour average pain severity scores recorded daily on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst pain). The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
94 participants
Primary outcome timeframe
Difference Scores (Visit 6-Baseline)
Results posted on
2018-10-03
Participant Flow
Participant milestones
| Measure |
Pregnenolone
Pregnenolone fixed escalating up to 500mg/day will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): 50mg PO, BID x 1 week, Visit 4 (week 2): 150mg PO, BID x 1 week, Visit 5 (week 3): 250mg PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered by 100mg per day and then discontinued.
Pregnenolone
|
Placebo
Placebo will be administered exactly the same as the active comparator (pregnenolone) and will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): placebo PO, BID x 1 week, Visit 4 (week 2): placebo PO, BID x 1 week, Visit 5 (week 3): placebo PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered in the exact manner as active study medication and then discontinued.
Placebo
|
|---|---|---|
|
Visit 3 (Randomization Visit)
STARTED
|
45
|
49
|
|
Visit 3 (Randomization Visit)
COMPLETED
|
45
|
49
|
|
Visit 3 (Randomization Visit)
NOT COMPLETED
|
0
|
0
|
|
Visit 4
STARTED
|
45
|
49
|
|
Visit 4
COMPLETED
|
45
|
48
|
|
Visit 4
NOT COMPLETED
|
0
|
1
|
|
Visit 5
STARTED
|
45
|
48
|
|
Visit 5
COMPLETED
|
44
|
47
|
|
Visit 5
NOT COMPLETED
|
1
|
1
|
|
Visit 6
STARTED
|
44
|
47
|
|
Visit 6
COMPLETED
|
41
|
42
|
|
Visit 6
NOT COMPLETED
|
3
|
5
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Neurosteroids as Novel Therapeutic Agents for Chronic Pain in OEF/OIF Veterans
Baseline characteristics by cohort
| Measure |
Pregnenolone
n=45 Participants
Pregnenolone fixed escalating up to 500mg/day will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): 50mg PO, BID x 1 week, Visit 4 (week 2): 150mg PO, BID x 1 week, Visit 5 (week 3): 250mg PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered by 100mg per day and then discontinued.
Pregnenolone
|
Placebo
n=49 Participants
Placebo will be administered exactly the same as the active comparator (pregnenolone) and will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): placebo PO, BID x 1 week, Visit 4 (week 2): placebo PO, BID x 1 week, Visit 5 (week 3): placebo PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered in the exact manner as active study medication and then discontinued.
Placebo
|
Total
n=94 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
45 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
94 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
37.48 years
STANDARD_DEVIATION 9.47 • n=5 Participants
|
37.55 years
STANDARD_DEVIATION 10.25 • n=7 Participants
|
37.52 years
STANDARD_DEVIATION 9.84 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
40 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
84 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
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 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
|
15 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
26 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
45 participants
n=5 Participants
|
49 participants
n=7 Participants
|
94 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Difference Scores (Visit 6-Baseline)Weekly mean of the 24-hour average pain severity scores recorded daily on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst pain). The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Outcome measures
| Measure |
Pregnenolone
n=41 Participants
Pregnenolone fixed escalating up to 500mg/day will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): 50mg PO, BID x 1 week, Visit 4 (week 2): 150mg PO, BID x 1 week, Visit 5 (week 3): 250mg PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered by 100mg per day and then discontinued.
Pregnenolone
|
Placebo
n=42 Participants
Placebo will be administered exactly the same as the active comparator (pregnenolone) and will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): placebo PO, BID x 1 week, Visit 4 (week 2): placebo PO, BID x 1 week, Visit 5 (week 3): placebo PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered in the exact manner as active study medication and then discontinued.
Placebo
|
|---|---|---|
|
Change in Pain Intensity Rating (Visit 6-Baseline)
|
4.11 units on a scale
Standard Error 0.18
|
4.67 units on a scale
Standard Error 0.17
|
SECONDARY outcome
Timeframe: Difference Scores of Averaged Pain Interference Domains (Visit 6-Baseline)The The Brief Pain Inventory (BPI) is a self-reported scale that measures the severity of pain and the interference of pain on function. The scores range from 0 (no pain) to 10 (pain as severe as you can imagine). There are 4 questions assessing worst pain, least pain, average pain in the past 24 hours, and the pain right now. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Outcome measures
| Measure |
Pregnenolone
n=41 Participants
Pregnenolone fixed escalating up to 500mg/day will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): 50mg PO, BID x 1 week, Visit 4 (week 2): 150mg PO, BID x 1 week, Visit 5 (week 3): 250mg PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered by 100mg per day and then discontinued.
Pregnenolone
|
Placebo
n=42 Participants
Placebo will be administered exactly the same as the active comparator (pregnenolone) and will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): placebo PO, BID x 1 week, Visit 4 (week 2): placebo PO, BID x 1 week, Visit 5 (week 3): placebo PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered in the exact manner as active study medication and then discontinued.
Placebo
|
|---|---|---|
|
Change in Pain Interference Scores (Visit 6-Baseline)
|
1.84 units on a scale
Standard Error 0.23
|
2.21 units on a scale
Standard Error 0.26
|
SECONDARY outcome
Timeframe: Difference Scores of BDI (Visit 6-Baseline)The Beck Depression Inventory is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression (Beck, et al., 1961). Scores range from 0 (no depression) to 63 (severe depression). The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Outcome measures
| Measure |
Pregnenolone
n=41 Participants
Pregnenolone fixed escalating up to 500mg/day will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): 50mg PO, BID x 1 week, Visit 4 (week 2): 150mg PO, BID x 1 week, Visit 5 (week 3): 250mg PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered by 100mg per day and then discontinued.
Pregnenolone
|
Placebo
n=42 Participants
Placebo will be administered exactly the same as the active comparator (pregnenolone) and will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): placebo PO, BID x 1 week, Visit 4 (week 2): placebo PO, BID x 1 week, Visit 5 (week 3): placebo PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered in the exact manner as active study medication and then discontinued.
Placebo
|
|---|---|---|
|
Change in Beck Depression Inventory (Visit 6-Baseline)
|
6.06 units on a scale
Standard Deviation 0.50
|
6.26 units on a scale
Standard Deviation 0.66
|
SECONDARY outcome
Timeframe: Difference Scores of Total DTS Scores (Visit 6-Baseline)The Davidson Trauma Scale (DTS) is a 17-item self-report measure that assesses the 17 DSM-IV symptoms of PTSD. Items are rated on 5-point frequency (0 = "not at all" to 4 = "every day") and severity scales (0 = "not at all distressing" to 4 = "extremely distressing"). Respondents are asked to identify the trauma that is most disturbing to them and to rate, in the past week, how much trouble they have had with each symptom. The DTS yields a frequency score (ranging from 0 to 68), severity score (ranging from 0 to 68), and total score (ranging from 0 to 136). The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Outcome measures
| Measure |
Pregnenolone
n=41 Participants
Pregnenolone fixed escalating up to 500mg/day will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): 50mg PO, BID x 1 week, Visit 4 (week 2): 150mg PO, BID x 1 week, Visit 5 (week 3): 250mg PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered by 100mg per day and then discontinued.
Pregnenolone
|
Placebo
n=42 Participants
Placebo will be administered exactly the same as the active comparator (pregnenolone) and will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): placebo PO, BID x 1 week, Visit 4 (week 2): placebo PO, BID x 1 week, Visit 5 (week 3): placebo PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered in the exact manner as active study medication and then discontinued.
Placebo
|
|---|---|---|
|
Change in Davidson Trauma Scale (Visit 6-Baseline)
|
17.71 units on a scale
Standard Error 1.93
|
15.04 units on a scale
Standard Error 11.70
|
SECONDARY outcome
Timeframe: Difference Z-Score (Visit 6-Baseline)The Tower of London is a clinician administered subtest from the Brief Assessment of Cognition-Affect (BAC-A) which measures executive functioning. Participants were shown two pictures simultaneously. Each picture showed three balls of different colors arranged on three pegs, with the balls in a unique arrangement in each picture. Participants were asked to give the total number of times the balls in one picture need to be moved in order to make the arrangement of balls identical to that of the other, opposing picture. There were 20 trials, 2 more were added if all 10 prior trials were correct. Range of scores was 0-22, higher scores are better. Z scores calculated and reported. The outcome measure is the change in Z scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Outcome measures
| Measure |
Pregnenolone
n=41 Participants
Pregnenolone fixed escalating up to 500mg/day will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): 50mg PO, BID x 1 week, Visit 4 (week 2): 150mg PO, BID x 1 week, Visit 5 (week 3): 250mg PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered by 100mg per day and then discontinued.
Pregnenolone
|
Placebo
n=42 Participants
Placebo will be administered exactly the same as the active comparator (pregnenolone) and will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): placebo PO, BID x 1 week, Visit 4 (week 2): placebo PO, BID x 1 week, Visit 5 (week 3): placebo PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered in the exact manner as active study medication and then discontinued.
Placebo
|
|---|---|---|
|
Change in Tower of London (Visit 6-Baseline)
|
0.71 units on a scale
Standard Deviation 0.08
|
0.76 units on a scale
Standard Deviation 0.07
|
SECONDARY outcome
Timeframe: Difference Z-Scores (Visit 6-Baseline)Digit Sequencing Task is a clinician administered subtest from the Brief Assessment of Cognition-Affect (BAC-A) which measures working memory and attention. Participants were presented with clusters of numbers of increasing length.They were asked to tell the experimenter the numbers in order, from lowest to highest. Measures: number of correct responses (range: 0-28, higher is better). Scores converted to Z-scores. The outcome measure is the change in Z scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Outcome measures
| Measure |
Pregnenolone
n=41 Participants
Pregnenolone fixed escalating up to 500mg/day will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): 50mg PO, BID x 1 week, Visit 4 (week 2): 150mg PO, BID x 1 week, Visit 5 (week 3): 250mg PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered by 100mg per day and then discontinued.
Pregnenolone
|
Placebo
n=42 Participants
Placebo will be administered exactly the same as the active comparator (pregnenolone) and will consist of the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): placebo PO, BID x 1 week, Visit 4 (week 2): placebo PO, BID x 1 week, Visit 5 (week 3): placebo PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered in the exact manner as active study medication and then discontinued.
Placebo
|
|---|---|---|
|
Change in Digit Sequence (Visit 6-Baseline)
|
0.79 units on a scale
Standard Deviation 0.06
|
0.74 units on a scale
Standard Deviation 0.07
|
Adverse Events
Pregnenolone
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
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 |
Pregnenolone
n=45 participants at risk
Pregnenolone fixed escalating up to 500mg/day with following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): 50mg PO, BID x 1 week, Visit 4 (week 2): 150mg PO, BID x 1 week, Visit 5 (week 3): 250mg PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered by 100mg per day and then discontinued.
Pregnenolone
|
Placebo
n=49 participants at risk
Placebo was administered exactly the same as the active comparator (pregnenolone) with the following schedule:
Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): placebo PO, BID x 1 week, Visit 4 (week 2): placebo PO, BID x 1 week, Visit 5 (week 3): placebo PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered in the exact manner as active study medication and then discontinued.
Placebo
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
2.2%
1/45 • Number of events 1 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
2.0%
1/49 • Number of events 1 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
|
General disorders
Decreased Appetite
|
2.2%
1/45 • Number of events 1 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
0.00%
0/49 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
|
Gastrointestinal disorders
Diarrhea
|
2.2%
1/45 • Number of events 2 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
0.00%
0/49 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
|
General disorders
Drowsiness
|
2.2%
1/45 • Number of events 1 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
2.0%
1/49 • Number of events 2 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
|
General disorders
Dry Mouth
|
2.2%
1/45 • Number of events 2 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
4.1%
2/49 • Number of events 2 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
|
General disorders
Headache
|
2.2%
1/45 • Number of events 2 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
4.1%
2/49 • Number of events 3 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
|
General disorders
Insomnia
|
2.2%
1/45 • Number of events 4 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
0.00%
0/49 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
|
General disorders
Myoclonus
|
0.00%
0/45 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
2.0%
1/49 • Number of events 1 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
|
General disorders
Nausea
|
0.00%
0/45 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
2.0%
1/49 • Number of events 1 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
|
General disorders
Paresthesia
|
0.00%
0/45 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
2.0%
1/49 • Number of events 1 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
|
General disorders
Tremor
|
0.00%
0/45 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
2.0%
1/49 • Number of events 2 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
|
General disorders
Urinary Retention
|
0.00%
0/45 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
4.1%
2/49 • Number of events 2 • Adverse Event data was collected at each visit throughout study participation and by phone two weeks post study completion, up to 8 weeks.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place