Trial Outcomes & Findings for Adjunctive Pregnenolone in Veterans With Mild TBI (NCT NCT00623506)

Last Updated: 2013-06-20

Results Overview

Mean change scores (Week 2 minus Week 10) to assess cognitive changes. The BAC-A includes brief assessments of executive functions, verbal fluency, attention, verbal memory, working memory and motor speed. Z-scores are calculated from composite scores. Higher z-scores are indicative of better cognitive performance, lower z-scores are indicative of lower cognitive performance. Range of z-scores anticipated to be between -3 and 3. Mean change scores from week 2 and week 10 (Week 2 minus Week 10).

Recruitment status

COMPLETED

Study phase

Target enrollment

30 participants

Primary outcome timeframe

Week 2, Week 10

Results posted on

2013-06-20

Participant Flow

Subjects were recruited from the Durham Medical Center, Durham, NC.

Each subject received a two week placebo-lead in following enrollment.

Participant milestones

Participant milestones
Measure	Pregnenolone Pregnenolone Pregnenolone : Pregnenolone 100 mg in divided doses (50 mg, PO, BID) Pregnenolone 300 mg in divided doses (150 mg, PO, BID) Pregnenolone 500 mg in divided doses (250 mg, PO, BID)	Placebo Placebo Subjects received placebo study medication; dispensed exactly as active study medication was dispensed.
Overall Study STARTED	15	15
Overall Study Week 4	11	11
Overall Study COMPLETED	11	11
Overall Study NOT COMPLETED	4	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Adjunctive Pregnenolone in Veterans With Mild TBI

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pregnenolone n=11 Participants Pregnenolone Pregnenolone : Pregnenolone 100 mg in divided doses (50 mg, PO, BID) Pregnenolone 300 mg in divided doses (150 mg, PO, BID) Pregnenolone 500 mg in divided doses (250 mg, PO, BID)	Placebo n=11 Participants Placebo Subjects received placebo study medication; dispensed exactly as active study medication was dispensed.	Total n=22 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	11 Participants n=5 Participants	11 Participants n=7 Participants	22 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	34.27 years STANDARD_DEVIATION 10.51 • n=5 Participants	36.38 years STANDARD_DEVIATION 9.74 • n=7 Participants	35.76 years STANDARD_DEVIATION 9.97 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Region of Enrollment United States	11 participants n=5 Participants	11 participants n=7 Participants	22 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 2, Week 10

Population: 22 out of 30 patients randomized completed 4 or more weeks of the study and were retained for data analysis. Statistics were completed using Last Observation Carried Forward (LOCF).

Outcome measures

Outcome measures
Measure	Pregnenolone n=11 Participants Pregnenolone Pregnenolone : Pregnenolone 100 mg in divided doses (50 mg, PO, BID) Pregnenolone 300 mg in divided doses (150 mg, PO, BID) Pregnenolone 500 mg in divided doses (250 mg, PO, BID)	Placebo n=11 Participants Placebo Subjects received placebo study medication; dispensed exactly as active study medication was dispensed.
Brief Assessment of Cognition in Affective Disorders (BAC-A)	0.61 units on a scale Standard Error 0.14	0.80 units on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: Week 2, Week 10

Population: 22 out of 30 patients randomized completed 4 or more weeks of the study and were retained for data analysis. Statistics were completed using LOCF.

Mean change scores (Week 2 minus Week 10) in posttraumatic stress disorder symptoms. Scores may range from 0 (no symptoms) to 136 (severe symptoms; score of 136 is based on the first 17 CAPS items administered). A reduced CAPS score indicates a reduction in (improvement) PTSD symptoms, while an increase in CAPS score indicates an increase (worsening) in PTSD symptoms.

Outcome measures

Outcome measures
Measure	Pregnenolone n=11 Participants Pregnenolone Pregnenolone : Pregnenolone 100 mg in divided doses (50 mg, PO, BID) Pregnenolone 300 mg in divided doses (150 mg, PO, BID) Pregnenolone 500 mg in divided doses (250 mg, PO, BID)	Placebo n=11 Participants Placebo Subjects received placebo study medication; dispensed exactly as active study medication was dispensed.
Clinician Administered PTSD Scale (CAPS)	-8.5 units on a scale Standard Error 3.22	-7.3 units on a scale Standard Error 4.74

SECONDARY outcome

Timeframe: Week 2, Week 10

Population: 22 out of 30 patients randomized completed 4 or more weeks of the study and were retained for data analysis. Statistics were completed using LOCF.

The QIDS total scores range from 0 to 27. Total score is obtained by adding the scores for each of the nine symptom domains of the DSM-IV Major Depressive Disorder (MDD) criteria: depressed mood,loss of interest or pleasure,concentration/decision making,self-outlook,suicidal ideation, energy/fatigability,sleep,weight/appetite change,and psychomotor changes. Each item is rated 0-3 (0=least or no severity, 3=greatest severity).

Outcome measures

Outcome measures
Measure	Pregnenolone n=11 Participants Pregnenolone Pregnenolone : Pregnenolone 100 mg in divided doses (50 mg, PO, BID) Pregnenolone 300 mg in divided doses (150 mg, PO, BID) Pregnenolone 500 mg in divided doses (250 mg, PO, BID)	Placebo n=11 Participants Placebo Subjects received placebo study medication; dispensed exactly as active study medication was dispensed.
Quick Inventory of Depressive Symptomatology (QIDS)	-1.09 units on a scale Standard Error 0.73	-0.54 units on a scale Standard Error 0.71

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

Additional Information

Christine E. Marx, MD

Durham VA Medical Center

Phone: 919 286-0411

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Pregnenolone n=11 participants at risk Pregnenolone Pregnenolone : Pregnenolone 100 mg in divided doses (50 mg, PO, BID) Pregnenolone 300 mg in divided doses (150 mg, PO, BID) Pregnenolone 500 mg in divided doses (250 mg, PO, BID)	Placebo n=11 participants at risk Placebo Subjects received placebo study medication; dispensed exactly as active study medication was dispensed.
General disorders Headache	27.3% 3/11 • Number of events 4 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Excitation and Agitation	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	0.00% 0/11 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Restlessness	0.00% 0/11 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Increased motor activity	0.00% 0/11 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Decreased Motor Activity	0.00% 0/11 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	9.1% 1/11 • Number of events 2 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Malaise	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Insomnia	0.00% 0/11 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	9.1% 1/11 • Number of events 2 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Hypersomnia	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	0.00% 0/11 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Drowsiness	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	27.3% 3/11 • Number of events 7 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Cramps	0.00% 0/11 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Akathisia	0.00% 0/11 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Dizziness	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Dry Mouth	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Blurred Vision	0.00% 0/11 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Constipation	0.00% 0/11 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Nausea	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Decreased Interest in Sex	9.1% 1/11 • Number of events 2 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	0.00% 0/11 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Impaired Sexual Performance	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Dermatological	18.2% 2/11 • Number of events 4 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	18.2% 2/11 • Number of events 4 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Muscle pain/stiffness	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	0.00% 0/11 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Decreased Appetite	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	0.00% 0/11 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.
General disorders Increased appetite	9.1% 1/11 • Number of events 1 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.	18.2% 2/11 • Number of events 4 • Adverse Events were collected following the one-week placebo-lead phase and at each subsequent study visit and telephone check-in. Adverse events were collected during 11 out of the 12 weeks.