Pregnenolone for Autism

Recruiting in Palo Alto (17 mi)

Overseen by Antonio Hardan, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Stanford University

Must not be taking: Steroid medications

Disqualifiers: Schizophrenia, Schizoaffective, Alcohol use, others

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing pregnenolone, a natural hormone in the brain, to see if it can help people with autism. Pregnenolone is part of a neurosteroid pathway that has been studied for its potential therapeutic value in stress and drug abuse-related disorders. The goal is to find out if it can reduce irritability and sensitivity to sensory differences, and improve social communication. Researchers hope this will lead to better treatments for autism.

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.

What data supports the effectiveness of the drug pregnenolone for autism?

Research shows that pregnenolone, a neurosteroid, can reduce irritability in adults with autism spectrum disorder, as seen in a study where participants showed significant improvement in irritability scores after 12 weeks of treatment. ^{1 2 3 4 5}

Is pregnenolone safe for use in humans?

Pregnenolone has been studied in people with autism and was generally well-tolerated, with no severe side effects reported. Some participants experienced mild issues like tiredness, diarrhea, and a low mood, but these were not common. ^{1 2 3 5 6}

How is the drug pregnenolone unique for treating autism?

Pregnenolone is a neurosteroid that may help reduce irritability in individuals with autism by modulating neurotransmission in the brain. Unlike other treatments, it is known for its role in enhancing neural development and memory, and it has been shown to be well-tolerated with minimal side effects. ^{1 2 4 5 6}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Placebo (Other)
• Pregnenolone (Corticosteroid)

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.

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Stanford University School of Medicine Stanford, CA

Who Is Running the Clinical Trial?

Stanford University Lead Sponsor

Simons Foundation Collaborator

References

1. United States 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? [2023] Pregnenolone is a neurosteroid with modulatory effects on γ-aminobutyric acid neurotransmission. Here, we aimed to evaluate the effectiveness and safety of pregnenolone add-on to risperidone in adolescents with autism spectrum disorders (ASD).

2. United States pubmed.ncbi.nlm.nih.gov

Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder. [2021] The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse effects. Pregnenolone yielded a statistically significant improvement in the primary measure, Aberrant Behavior Checklist (ABC)-Irritability [from 17.4 ± 7.4 at baseline to 11.2 ± 7.0 at 12 weeks (p = 0.028)]. Secondary measures were not statistically significant with the exception of ABC-lethargy (p = 0.046) and total Short Sensory Profile score (p = 0.009). No significant vital sign changes occurred during this study. Pregnenolone was not associated with any severe side effects. Single episodes of tiredness, diarrhea and depressive affect that could be related to pregnenolone were reported. Overall, pregnenolone was modestly effective and well-tolerated in individuals with ASD.

3. England 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. [2019] Hydroxylations of pregnenolone (PREG) at the 7 alpha- and 7 beta-positions have been reported in numerous murine tissues and organs and responsible cytochrome P450 (CYP) species await identification. Using thin layer chromatography and gas chromatography-mass spectrometry, we report identification of 7 alpha-hydroxy-PREG and 7 beta-hydroxy-PREG metabolites produced in mouse brain microsome digests and kinetic studies of their production with apparent KM values of 0.5 +/- 0.1 microM and 5.1 +/- 0.6 microM for 7 alpha- and 7 beta-hydroxylation respectively. Investigation of CYP inhibitors and of steroid hormone effects on both 7 alpha- and 7 beta-hydroxylations of PREG showed that: (i) different CYP were involved in 7 alpha- and 7 beta-hydroxylation of PREG because solely 7 alpha-hydroxylation was extensively inhibited by metyrapone, alpha-naphthoflavone, ketoconazole and 3 beta-hydroxysteroids, (ii) CYP 1A2, 2D6, 2B1 and 2B11 were not responsible for 7 alpha- and 7 beta-hydroxylation of PREG because respective specific inhibitors furafylline, quinidine and chloramphenicol triggered no inhibition, (iii) CYP 1A1 was responsible for only part of the 7 beta-hydroxylation of PREG because use of alpha-naphthoflavone, which inhibits specifically CYP 1A1, did not suppress entirely 7 beta-hydroxylation, while ketoconazole, metyrapone and antipyrine, which do not inhibit CYP 1A1, decreased part of the 7 beta-hydroxylation, (iv) 7 alpha-hydroxylation of PREG may be shared with other 3 beta-hydroxysteroids such as isoandrosterone and 5-androstene-3 beta,17 beta-diol which were strong inhibitors, but not with dehydroepiandrosterone which was a non-competitive inhibitor as weak as 3-oxosteroids, and (v) 7 beta-hydroxylation of PREG was not markedly changed by other steroids. Taken together, these findings will be of use for identification of the CYP species responsible for 7 alpha- and 7 beta-hydroxylation of PREG and for studies of their activities in brain.

4. Germany pubmed.ncbi.nlm.nih.gov

Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia. [2021] Preclinical and clinical data suggest that pregnenolone may be a promising therapeutic in schizophrenia. Pregnenolone is neuroprotective and enhances learning and memory, myelination, and microtubule polymerization. Treatment with pregnenolone elevates allopregnanolone (a neurosteroid that enhances GABAA receptor responses) and pregnenolone sulfate (a positive NMDA receptor modulator). Pregnenolone could thus potentially mitigate GABA dysregulation and/or NMDA receptor hypofunction in schizophrenia via metabolism to other neurosteroids.

5. England pubmed.ncbi.nlm.nih.gov

A synthetic pregnenolone analog promotes microtubule dynamics and neural development. [2022] Pregnenolone (P5) is a neurosteroid that promotes microtubule polymerization. It also reduces stress and negative symptoms of schizophrenia, promotes memory, as well as recovery from spinal cord injury. P5 is the first substance in the steroid-synthetic pathway; it can be further metabolized into other steroids. Therefore, it is difficult to differentiate the roles of P5 versus its metabolites in the brain. To alleviate this problem, we synthesized and screened a series of non-metabolizable P5 derivatives for their ability to polymerize microtubules similar to P5.

6. England 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. [2023] Pregnenolone is a precursor of various steroid hormones involved in osteoblast proliferation, microtubules polymerization and cell survival protection. Previous reports focused on the effects of pregnenolone metabolites on stem cell proliferation and differentiation; however, the effects of pregnenolone itself has not been well explored. The present study aimed to investigate the role of pregnenolone on NSC proliferation and to determine the doses required for NSC differentiation as well as the various genes involved in its mechanism of action.