A Study of Pregnenolone in the Treatment of Individuals With Autism

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01881737
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arm: 1
• Duration (Months): 26.1
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This study will assess the tolerability and effectiveness of pregnenolone in the treatment of behavioral deficits in adults with autism. Pregnenolone is a naturally occurring hormone found in the body which has been shown to help with the function of nerve cells. It is also shown to modulate the activity of certain brain receptors implicated in autism. We hope to examine the tolerability of pregnenolone in adults with autism.

Condition or Disease	Intervention/Treatment	Phase
Autistic Disorder	Drug: Pregnenolone	Phase 2

Detailed Description

This study will assess the tolerability and effectiveness of pregnenolone in the treatment of behavioral deficits in adults with autism. Pregnenolone is a naturally occurring hormone found in the body which has been shown to help with the function of nerve cells. It is also shown to modulate the activity of certain brain receptors implicated in autism.

Pregnenolone has been used safely in research studies involving individuals with schizophrenia. In the proposed trial, we hope to examine the tolerability of pregnenolone in adults with autism. We hope to see improvement in behavioral outcomes as measured by standardized behavioral measures. Further, we will measure concentrations of pregnenolone and related neuroactive compounds in the blood. The use of pregnenolone has been studied in a number of mental disorders but not autism. Thus, we hope the study will identify new avenues of research for the treatment of autism.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Pilot Study of Pregnenolone in the Treatment of Individuals With Autism
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Pregnenolone Pregnenolone up to 500 mg per day

Drug: Pregnenolone; With Baseline serving as approximately day 1, twice daily intake of orally administered pregnenolone will occur on a schedule consisting of an up-titration followed by a down-titration as described below. Week 1 and 2: 100 mg Week 3 and 4: 200 mg Week 5 and 6: 300 mg Week 7 and 8: 400 mg Week 9 -12: 500 mg At the end of Week 12, pregnenolone was decreased by 50 mg twice a day every 3 days until it was discontinued. If the participant is unable to tolerate a specific dose then he/she will be maintained at the highest tolerated dose until down titration occurs.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events According to Dosage Record and Treatment Emergent Symptom (DOTES) as Assessed at All Follow-up Visits (2, 4, 6, 8, 10, 12, and 16 Weeks) [2, 4, 6, 8, 10, 12, and 16 weeks]

Secondary Outcome Measures

1. Social Responsiveness Scale (SRS) Total Score [12 weeks]

   SRS total score (total range 0-195); higher scores mean more abnormal social behaviors.

2. Sensory Profile Questionnaire Total Score [12]

   scores on a scale (range: 38-190); lower scores mean more abnormal sensory problems.

3. Vineland Adaptive Behavior Scale [12 weeks]

   Adaptive Behavior Composite Score (score range 20-160); higher scores mean more typical adaptive behaviors.

4. Repetitive Behavior Scale [12 weeks]

5. Pregnenolone Level in Peripheral Blood as Measured at Baseline and After 12 Weeks [12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Outpatients 18-45 years of age;

2. Males and females who are physically healthy;

3. Diagnosis of autism based on Diagnostic and Statistical Manual (DSM-IV-TR) criteria, the Autism Diagnostic Interview-Revised, and expert clinical evaluation;

4. Total Aberrant Behavior Checklist (ABC) greater then 21;

5. Care provider who can reliably bring subject to clinic visits, can provide trustworthy ratings, and interacts with subject on a regular basis;

6. Ability of subject to swallow the compound;

7. Stable concomitant medications for at least 2 weeks; and

8. No planned changes in psychosocial interventions during the open-label pregnenolone trial.

Exclusion Criteria:

1. Diagnostic and Statistical Manual (DSM-IV-TR) diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder, not otherwise specified;

2. Prior adequate trial of pregnenolone;

3. Active medical problems: unstable seizures, significant physical illness (e.g., serious liver or renal pathology);

4. Pregnancy or sexually active females (as determined by a urinary pregnancy test in the beginning of the study); and

5. Subjects taking oil or fat based nutritional supplements will be excluded from the study unless they have been off these compounds for at least 4 weeks

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Antonio Hardan, MD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Antonio Hardan, Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT01881737
• Other Study ID Numbers: SU-08092011-8246
• First Posted: Jun 20, 2013
• Last Update Posted: Mar 29, 2017
• Last Verified: Feb 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Antonio Hardan, Professor, Stanford University: autism
• Additional relevant MeSH terms: Autistic Disorder

Study Results

Participant Flow

Recruitment Details	Participants recruited between November 2011 and September 2013 at Stanford University.

Arm/Group Title	Pregnenolone
Arm/Group Description	Open-Label Trial
Period Title: Overall Study
STARTED	15
Number Screened	15
COMPLETED	10
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Pregnenolone
Arm/Group Description	Twice daily intake of orally administered pregnenolone will occur on a schedule consisting of an up-titration followed by a down-titration as described below. Week 1 and 2: 100 mg Week 3 and 4: 200 mg Week 5 and 6: 300 mg Week 7 and 8: 400 mg Week 9 -12: 500 mg At the end of Week 12, pregnenolone was decreased by 50 mg twice a day every 3 days until it was discontinued. If the participant is unable to tolerate a specific dose then he/she will be maintained at the highest tolerated dose until down titration occurs.
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22.5 (5.8)
Sex: Female, Male (Count of Participants)
Female	2 16.7%
Male	10 83.3%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events According to Dosage Record and Treatment Emergent Symptom (DOTES) as Assessed at All Follow-up Visits (2, 4, 6, 8, 10, 12, and 16 Weeks)
Time Frame	2, 4, 6, 8, 10, 12, and 16 weeks

Outcome Measure Data

Analysis Population Description

During the 12-week treatment period, two participants dropped out of the study. The follow-up observations for the two participants who dropped out were included in the analyses.

Arm/Group Title	Pregnenolone
Arm/Group Description	Open-Label study
Measure Participants	12
Tiredness	1 8.3%
Diarrhea	2 16.7%
Depressive Affect	2 16.7%
Increased Excitement/Agitation	3 25%
Sleep Problems	1 8.3%
Drowsiness	1 8.3%
Anorexia/Decreased Appetite	2 16.7%
Increased Motor Activity	1 8.3%
Sweating	1 8.3%
Constipation	1 8.3%
Tremor	1 8.3%

2. Secondary Outcome

Title	Social Responsiveness Scale (SRS) Total Score
Description	SRS total score (total range 0-195); higher scores mean more abnormal social behaviors.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pregnenolone
Arm/Group Description	Pregnenolone up to 500 mg per day Pregnenolone: With Baseline serving as approximately day 1, twice daily intake of orally administered pregnenolone will occur on a schedule consisting of an up-titration followed by a down-titration as described below. Week 1 and 2: 100 mg Week 3 and 4: 200 mg Week 5 and 6: 300 mg Week 7 and 8: 400 mg Week 9 -12: 500 mg At the end of Week 12, pregnenolone was decreased by 50 mg twice a day every 3 days until it was discontinued. If the participant is unable to tolerate a specific dose then he/she will be maintained at the highest tolerated dose until down titration occurs.
Measure Participants	12
Baseline SRS Total Score	84.9 (8.1)
Week 12 SRS Total Score	84.5 (9.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregnenolone
	Comments	Effect Size Cohen's d = -0.05
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.848
	Comments
	Method	Paired t test
	Comments

3. Secondary Outcome

Title	Sensory Profile Questionnaire Total Score
Description	scores on a scale (range: 38-190); lower scores mean more abnormal sensory problems.
Time Frame	12

Outcome Measure Data

Analysis Population Description

During the 12-week treatment period, two participants dropped out of the study. The follow-up observations for one of the participants who dropped out were included in the analyses.

Arm/Group Title	Pregnenolone
Arm/Group Description	Twice daily intake of orally administered pregnenolone will occur on a schedule consisting of an up-titration followed by a down-titration as described below. Week 1 and 2: 100 mg Week 3 and 4: 200 mg Week 5 and 6: 300 mg Week 7 and 8: 400 mg Week 9 -12: 500 mg At the end of Week 12, pregnenolone was decreased by 50 mg twice a day every 3 days until it was discontinued. If the participant is unable to tolerate a specific dose then he/she will be maintained at the highest tolerated dose until down titration occurs.
Measure Participants	11
Baseline Score on the Sensory Profile	137.7 (21.5)
Week 12 Score on the Sensory Profile	147.6 (15.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregnenolone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	Paired t test
	Comments	Effect Size Cohen's d = 0.53

4. Secondary Outcome

Title	Vineland Adaptive Behavior Scale
Description	Adaptive Behavior Composite Score (score range 20-160); higher scores mean more typical adaptive behaviors.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pregnenolone
Arm/Group Description	Twice daily intake of orally administered pregnenolone will occur on a schedule consisting of an up-titration followed by a down-titration as described below. Week 1 and 2: 100 mg Week 3 and 4: 200 mg Week 5 and 6: 300 mg Week 7 and 8: 400 mg Week 9 -12: 500 mg At the end of Week 12, pregnenolone was decreased by 50 mg twice a day every 3 days until it was discontinued. If the participant is unable to tolerate a specific dose then he/she will be maintained at the highest tolerated dose until down titration occurs.
Measure Participants	12
Baseline Vineland Adaptive Behavior Score	37.3 (13.1)
Week 12 Vineland Adaptive Behavior Score	42.9 (16.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregnenolone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	paired t test
	Comments	Effect size Cohen's d = 0.38

5. Secondary Outcome

Title	Repetitive Behavior Scale
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Data were not collected for this Outcome Measure because the total score is not a very valid measure of receptive behaviors.

Arm/Group Title	Pregnenolone
Arm/Group Description	Twice daily intake of orally administered pregnenolone will occur on a schedule consisting of an up-titration followed by a down-titration as described below. Week 1 and 2: 100 mg Week 3 and 4: 200 mg Week 5 and 6: 300 mg Week 7 and 8: 400 mg Week 9 -12: 500 mg At the end of Week 12, pregnenolone was decreased by 50 mg twice a day every 3 days until it was discontinued. If the participant is unable to tolerate a specific dose then he/she will be maintained at the highest tolerated dose until down titration occurs.
Measure Participants	0

6. Secondary Outcome

Title	Pregnenolone Level in Peripheral Blood as Measured at Baseline and After 12 Weeks
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

During the 12-week treatment period, two participants dropped out of the study. The follow-up observations for one of the participants who dropped out were included in the analyses.

Arm/Group Title	Pregnenolone
Arm/Group Description	Twice daily intake of orally administered pregnenolone will occur on a schedule consisting of an up-titration followed by a down-titration as described below. Week 1 and 2: 100 mg Week 3 and 4: 200 mg Week 5 and 6: 300 mg Week 7 and 8: 400 mg Week 9 -12: 500 mg At the end of Week 12, pregnenolone was decreased by 50 mg twice a day every 3 days until it was discontinued. If the participant is unable to tolerate a specific dose then he/she will be maintained at the highest tolerated dose until down titration occurs.
Measure Participants	11
Baseline level	1.9 (0.7)
Week 12	7.0 (4.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregnenolone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Time Frame: Baseline, 2, 4, 6, 8, 10, 12, and 16 weeks
Arm/Group Title	Pregnenolone
Arm/Group Description	Pregnenolone was not associated with any severe adverse effects. Single episodes of tiredness (n = 1), diarrhea (n = 1), and depressive affect (n = 1) that could possibly be related to pregnenolone were reported. A few other adverse events with remote chance to be related to the medication were reported: increased excitement/agitation (n = 3), sleep problems (n = 1), drowsiness (n = 1), anorexia/decreased appetite (n = 2), increased motor activity (n = 1), sweating (n = 1), constipation (n = 1), diarrhea (n = 1), tremor (n = 1), and depressive affect (n = 1). No significant vital sign or EKG changes occurred in any study participants. No abnormal laboratory tests were caused by pregnenolone.
All Cause Mortality
	Pregnenolone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pregnenolone
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Other (Not Including Serious) Adverse Events
	Pregnenolone
	Affected / at Risk (%)	# Events
Total	6/12 (50%)
Gastrointestinal disorders
Diarrhea	2/12 (16.7%)	2
Anorexia/Decreased Appetite	2/12 (16.7%)	2
Constipation	1/12 (8.3%)	1
General disorders
Tiredness	1/12 (8.3%)	1
Sleep Problems	1/12 (8.3%)	1
Drowsiness	1/12 (8.3%)	1
Increased Motor Activity	1/12 (8.3%)	1
Sweating	1/12 (8.3%)	1
Tremor	1/12 (8.3%)	1
Psychiatric disorders
Depressive Affect	2/12 (16.7%)	2
Increased Excitement/Agitation	3/12 (25%)	3

Limitations/Caveats

This is an open-label trial with a very small sample size. No measures of plasma or salivary concentrations of metabolites were completed in this study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.