Pregnenolone for Autism

Overseen By Lawrence K. Fung, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Steroid medications

Disqualifiers: Schizophrenia, Schizoaffective, Alcohol use, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 14 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pregnenolone, a naturally occurring hormone in the brain, to determine its effects on irritability, sensory sensitivity, and social communication in people with autism. Researchers aim to assess the safety and effectiveness of pregnenolone for these symptoms. Participants will be divided into two groups: one will receive pregnenolone, and the other will receive a placebo (a harmless pill with no active ingredient). This trial targets physically healthy individuals with autism who experience frequent irritability and maintain stable medication use. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that participants have stable medications for at least 2 weeks before joining, and they cannot be taking steroid medications.

Is there any evidence suggesting that pregnenolone is likely to be safe for humans?

Research has shown that pregnenolone, a natural hormone in the brain, has been studied for its safety and potential benefits in treating various mental health conditions. Although specific safety information for individuals with autism is limited, studies in other areas provide some insights.

Pregnenolone supports brain health and cognitive function. It helps produce other important hormones, suggesting it plays a key role in maintaining the body's balance.

Generally, pregnenolone is considered safe for many people. However, like any treatment, it can cause side effects, such as headaches or fatigue. Since this trial is in an early stage, the primary goal is to assess how well participants tolerate the treatment and to monitor for any side effects.

Consult a healthcare provider to weigh the potential benefits and risks before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for autism?

Pregnenolone is unique for autism treatment because it is a naturally occurring steroid hormone that acts on the brain, potentially improving symptoms by modulating neurosteroid pathways. Unlike traditional medications for autism, which often focus on behavioral symptoms or neurotransmitter regulation, pregnenolone targets the underlying neurochemical environment. Researchers are excited about its potential to address core symptoms of autism by offering a new mechanism of action that isn't covered by current treatments like antipsychotics or selective serotonin reuptake inhibitors (SSRIs). This could mean more comprehensive symptom management with potentially fewer side effects.

What evidence suggests that pregnenolone might be an effective treatment for autism?

Research has shown that pregnenolone, a hormone naturally found in the brain, might help with autism symptoms. Studies have found it can lower irritability and improve social interactions in people with autism spectrum disorder (ASD). Pregnenolone likely works by calming the brain and reducing overstimulation. Participants who took pregnenolone reported feeling less socially withdrawn and irritable. In this trial, participants will receive either pregnenolone or a placebo to evaluate its effectiveness. These findings suggest that pregnenolone could be a promising option for managing some autism symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Antonio Hardan, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for healthy males and females aged 14-25 with Autism Spectrum Disorder (ASD), confirmed by specific diagnostic tools. Participants must have a certain level of irritability and severity of ASD symptoms, be in the late stages of puberty, and on stable medications without changes planned during the study. Those with unstable seizures, significant illness, other major psychiatric disorders, or women who are pregnant or not using contraception cannot join.

Inclusion Criteria

I am between 14 and 25 years old and have reached a late stage of puberty.

I am physically healthy.

My medications have not changed in the last 2 weeks.

Exclusion Criteria

I am not pregnant or I use birth control if sexually active.

I am currently taking steroid medications.

You have already tried the medication pregnenolone in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pregnenolone with increasing doses over 14 weeks to assess tolerability and effectiveness

14 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Pregnenolone

Trial Overview

The study tests pregnenolone's safety and effectiveness compared to a placebo in reducing irritability, improving sensitivity to sensory differences, and enhancing social communication in individuals with autism. Pregnenolone is a hormone thought to help various psychiatric conditions.

How Is the Trial Designed?

Group I: Pregnenolone (up to 500 mg per day) Experimental Treatment 1 Intervention

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)

Group II: Placebo Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Simons Foundation

Collaborator

Trials

8

Recruited

101,000+

Published Research Related to This Trial

The study identified two metabolites, 7 alpha-hydroxy-PREG and 7 beta-hydroxy-PREG, produced in mouse brain microsomes, with different kinetic properties indicating distinct enzymatic pathways for their production.

Different cytochrome P450 (CYP) enzymes are involved in the hydroxylation of pregnenolone, with specific inhibitors revealing that 7 alpha-hydroxylation is primarily inhibited by certain compounds, while 7 beta-hydroxylation involves CYP 1A1 and other unidentified enzymes, providing insights for future research on these metabolic processes in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cytochrome P450 inhibitors and of steroid hormones on the formation of 7-hydroxylated metabolites of pregnenolone in mouse brain microsomes. Doostzadeh, J., Morfin, R.[2019]

Pregnenolone at a dose of 10 μM was found to be optimal for promoting the proliferation of neural stem cells (NSCs), significantly increasing the number of neurospheres compared to controls.

Lower doses of pregnenolone (5 and 10 μM) enhanced NSC differentiation into oligodendrocytes, while higher doses (15 μM) promoted differentiation into neurons, indicating that pregnenolone can regulate NSC fate depending on the concentration used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnenolone enhances the proliferation of mouse neural stem cells and promotes oligodendrogenesis, together with Sox10, and neurogenesis, along with Notch1 and Pax6. Negintaji, K., Ghanbari, A., Frozanfar, M., et al.[2023]

A new compound, 3-beta-pregnenolone acetate (compound #43), was developed as a non-metabolizable derivative of pregnenolone (P5) and was found to effectively promote microtubule polymerization, similar to P5.

Compound #43 demonstrated significant effects in live cells, including increased neurite outgrowth and stable microtubule formation in zebrafish, suggesting its potential as a therapeutic candidate for neurodevelopmental diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A synthetic pregnenolone analog promotes microtubule dynamics and neural development. Kolas, V., Bandonil, JSA., Wali, N., et al.[2022]

In a 12-week pilot study involving 12 young adults with autism spectrum disorder, pregnenolone significantly reduced irritability, as measured by the Aberrant Behavior Checklist, with scores improving from 17.4 to 11.2 (p = 0.028).

Pregnenolone was well-tolerated with no severe side effects reported, and only mild adverse effects like tiredness and diarrhea were noted, indicating its safety for use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder. Fung, LK., Libove, RA., Phillips, J., et al.[2021]

In a randomized controlled trial involving 120 participants with schizophrenia, pregnenolone treatment for 8 weeks significantly improved functional capacity compared to placebo, particularly in communication skills.

While pregnenolone did not show significant effects on cognitive symptoms, it was well-tolerated and serum levels of pregnenolone correlated with functional improvements in female participants, suggesting potential as a therapeutic option for schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia. Marx, CE., Lee, J., Subramaniam, M., et al.[2021]

In a study of 64 adolescents with autism spectrum disorders, adding pregnenolone to risperidone treatment showed significant improvements in irritability, stereotypy, and hyperactivity, suggesting it may enhance the effectiveness of standard treatment.

The addition of pregnenolone did not increase the frequency or severity of adverse effects compared to placebo, indicating it is a safe adjunct therapy for managing symptoms of ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Pregnenolone Adjunct to Risperidone Ameliorate Irritable Behavior in Adolescents With Autism Spectrum Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial? Ayatollahi, A., Bagheri, S., Ashraf-Ganjouei, A., et al.[2023]

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