Pilot Trial of Pregnenolone in Autism

Randomized Controlled Pilot Trial of Pregnenolone in Autism

This is a research study to examine the tolerability and effectiveness of pregnenolone in individuals with autism. Pregnenolone is a naturally occurring steroid hormone in the brain that has been implicated in treating various psychiatric conditions. The investigators hope to learn the effects and safety of using pregnenolone in reducing irritability and sensitivity to sensory differences and improving social communication in individuals with autism. The investigators hope by studying the effects of pregnenolone in more detail, the investigators can design better ways to treat individuals with autism.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder; Autism
• Intervention / Treatment: Drug: Pregnenolone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• outpatients between 14 and 25 years of age with a Tanner stage of IV or V;
• male and female subjects who were physically healthy;
• diagnosis of Autism Spectrum Disorder (ASD) based on DSM-5, expert clinical opinion and confirmed with Autism Diagnostic Interview - Revised (ADI-R) and either Autism Diagnostic Observation Schedule (ADOS) or Childhood Autism Rating Scale (CARS-2);
• Aberrant Behavior Checklist -Irritability (ABC-I)≥ 18 and Clinical Global Impression (CGI)-Severity subscale ≥ 4;
• stable concomitant medications for at least 2 weeks;
• no planned changes in psychosocial interventions during the trial.

Exclusion Criteria:

• Diagnostic and Statistical Manual (DSM-5) diagnosis of schizophrenia, schizoaffective disorder, alcohol use disorder;
• prior adequate trial of pregnenolone;
• active medical problems: unstable seizures (>2 in past month), significant physical illness;
• pregnant or sexually active female subjects who do not adhere to use an appropriate form of external prophylactics;
• participants taking steroid medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; orally administered placebo capsules
Experimental: Pregnenolone (up to 500 mg per day); Twice daily intake of orally administered Pregnenolone will occur on a schedule as described below. Weeks 1 and 2: 30mg twice daily (total 60mg per day) Weeks 3 and 4: 60mg twice daily (total: 120mg per day) Weeks 5 and 6: 90mg twice daily (total: 180mg per day) Weeks 7 and 8: 150mg twice daily (total: 300mg per day) Weeks 9 and 10: 210mg twice daily (total: 420mg per day) Weeks 11 to 14: 250mg twice daily (total: 500mg per day)	Drug: Pregnenolone; orally administered Pregnenolone capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in parent rated Aberrant Behavior Checklist Irritability (ABC-I) score during treatment	2-week, 4-week, 6-week, 8-week, 10-week, 14-week

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in parent rated Aberrant Behavior Checklist (ABC) scores during treatment	2-week, 4-week, 6-week, 8-week, 10-week, 14-week
Change from baseline in parent rated Sensory Profile Questionnaire (SPQ) scores during treatment	2-week, 4-week, 6-week, 8-week, 10-week, 14-week
Change from baseline in Vineland Adaptive Behavior Scales Second Edition (VABS-II)	2-week, 6-week, 10-week, 14-week
Change from baseline in Clinical Global Impression (CGI) scores during treatment	2-week, 4-week, 6-week, 8-week, 10-week, 14-week
Change from baseline in levels of pregnenolone and its related neurosteroids in peripheral blood	14-week
Change from baseline on the Autism Diagnostic Observation Schedule (ADOS)	14-week
Change from baseline in laboratory based eye-gaze measures	14-week
Change from baseline in laboratory based electroencephalography (EEG) measures	14-week
Change from baseline in laboratory clinical lab values including complete metabolic panel, complete blood count with differential, cholesterol panel and routine urinalysis.	14-week
Change from baseline in parent rated Social Responsiveness Scale (SRS) scores during treatment	2-week, 6-week, 10-week, 14-week
Change from baseline on the Dosage Record Treatment Emergent Symptom Scale (DOTES) scores during treatment	2-week, 4-week, 6-week, 8-week, 10-week, 14-week

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Simons Foundation
• Investigators: Principal Investigator: Antonio Y. Hardan, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2016
• Primary Completion (Actual): March 13, 2026
• Study Completion (Actual): March 17, 2026

Study Registration Dates

• First Submitted: December 2, 2015
• First Submitted That Met QC Criteria: December 10, 2015
• First Posted (Estimated): December 11, 2015

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Autism; Autism Spectrum Disorder; Pregnenolone
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Gonadal Steroid Hormones; Gonadal Hormones; Pregnenes; Hydroxycorticosteroids; Adrenal Cortex Hormones; Progesterone Congeners; Pregnenolone
• Other Study ID Numbers: IRB-34762

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES