Autistic Disorder
Conditions
Keywords
autism
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.
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.
Interventions
DRUGPregnenolone
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.
Sponsors
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Social Responsiveness Scale (SRS) Total Score | 12 weeks | SRS total score (total range 0-195); higher scores mean more abnormal social behaviors. |
| Sensory Profile Questionnaire Total Score | 12 | scores on a scale (range: 38-190); lower scores mean more abnormal sensory problems. |
| Vineland Adaptive Behavior Scale | 12 weeks | Adaptive Behavior Composite Score (score range 20-160); higher scores mean more typical adaptive behaviors. |
| Repetitive Behavior Scale | 12 weeks | — |
| Pregnenolone Level in Peripheral Blood as Measured at Baseline and After 12 Weeks | 12 weeks | — |
Countries
United States
Participant flow
Recruitment details
Participants recruited between November 2011 and September 2013 at Stanford University.
Participants by arm
| Arm | Count |
|---|---|
| Pregnenolone 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. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Inclusion/Exclusion Criteria Not Met | 3 |
| Overall Study | Withdrawal by Subject | 1 |
| Overall Study | Worsening of baseline behavior | 1 |
Baseline characteristics
| Characteristic | Pregnenolone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 22.5 years STANDARD_DEVIATION 5.8 |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregnenolone | 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) | Tiredness | 1 participants |
| Pregnenolone | 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) | Diarrhea | 2 participants |
| Pregnenolone | 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) | Depressive Affect | 2 participants |
| Pregnenolone | 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) | Sleep Problems | 1 participants |
| Pregnenolone | 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) | Drowsiness | 1 participants |
| Pregnenolone | 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) | Anorexia/Decreased Appetite | 2 participants |
| Pregnenolone | 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) | Increased Motor Activity | 1 participants |
| Pregnenolone | 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) | Sweating | 1 participants |
| Pregnenolone | 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) | Constipation | 1 participants |
| Pregnenolone | 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) | Tremor | 1 participants |
| Pregnenolone | 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) | Increased Excitement/Agitation | 3 participants |
Secondary
Pregnenolone Level in Peripheral Blood as Measured at Baseline and After 12 Weeks
Time frame: 12 weeks
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregnenolone | Pregnenolone Level in Peripheral Blood as Measured at Baseline and After 12 Weeks | Week 12 | 7.0 ng/ml | Standard Deviation 4.1 |
| Pregnenolone | Pregnenolone Level in Peripheral Blood as Measured at Baseline and After 12 Weeks | Baseline level | 1.9 ng/ml | Standard Deviation 0.7 |
p-value: 0.0001t-test, 2 sided
Secondary
Repetitive Behavior Scale
Time frame: 12 weeks
Population: Data were not collected for this Outcome Measure because the total score is not a very valid measure of receptive behaviors.
Secondary
Sensory Profile Questionnaire Total Score
scores on a scale (range: 38-190); lower scores mean more abnormal sensory problems.
Time frame: 12
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregnenolone | Sensory Profile Questionnaire Total Score | Baseline Score on the Sensory Profile | 137.7 scores on a scale (range: 38-190) | Standard Deviation 21.5 |
| Pregnenolone | Sensory Profile Questionnaire Total Score | Week 12 Score on the Sensory Profile | 147.6 scores on a scale (range: 38-190) | Standard Deviation 15.3 |
p-value: 0.009Paired t test
Secondary
Social Responsiveness Scale (SRS) Total Score
SRS total score (total range 0-195); higher scores mean more abnormal social behaviors.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregnenolone | Social Responsiveness Scale (SRS) Total Score | Baseline SRS Total Score | 84.9 SRS total score (total range 0-195) | Standard Deviation 8.1 |
| Pregnenolone | Social Responsiveness Scale (SRS) Total Score | Week 12 SRS Total Score | 84.5 SRS total score (total range 0-195) | Standard Deviation 9.2 |
Comparison: Effect Size Cohen's d = -0.05p-value: 0.848Paired t test
Secondary
Vineland Adaptive Behavior Scale
Adaptive Behavior Composite Score (score range 20-160); higher scores mean more typical adaptive behaviors.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregnenolone | Vineland Adaptive Behavior Scale | Baseline Vineland Adaptive Behavior Score | 37.3 score (range 20-160) | Standard Deviation 13.1 |
| Pregnenolone | Vineland Adaptive Behavior Scale | Week 12 Vineland Adaptive Behavior Score | 42.9 score (range 20-160) | Standard Deviation 16.5 |
p-value: 0.38paired t test