84 Participants Needed

Pregnenolone for Anxiety and Depression

JC
CE
Overseen ByChristine E Marx, MD MA
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: VA Office of Research and Development
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

Will I have to stop taking my current medications?

You won't have to stop taking your current psychiatric medications, but you can't change them for 4 weeks before starting the study. If you're using benzodiazepines or opioids, you can't participate in the trial.

What evidence supports the effectiveness of the drug pregnenolone for anxiety and depression?

Research suggests that pregnenolone may help improve mood in people with mood disorders, as one study found it led to a reduction in depressive symptoms in patients with a history of substance use. Additionally, it showed some effectiveness in reducing irritability in adults with autism spectrum disorder, which may indirectly suggest potential benefits for mood-related conditions.12345

Is pregnenolone generally safe for humans?

The research does not provide specific safety data for pregnenolone in humans, but it does mention that pregnenolone can affect anxiety levels in mice and interacts with other substances like ethanol. Further studies are needed to determine its safety in humans.56789

How is the drug pregnenolone unique for treating anxiety and depression?

Pregnenolone is unique because it is a neurosteroid that may improve mood and depressive symptoms by affecting brain receptors and possibly interacting with microtubule associated protein 2 (MAP2), which is a novel target for antidepressant therapy. It has shown potential benefits in mood disorders, especially in patients with bipolar disorder, and is generally well-tolerated.1371011

What is the purpose of this trial?

Anxiety and depression symptoms occur at high rates in Veteran populations and can significantly impact function, compromising the ability to work and to successfully form and maintain valued relationships. Several other symptoms commonly occur with anxiety and depression, including poor sleep quality and chronic pain. Since all these symptoms frequently occur together, they may have a common underlying biological basis. A single medication that could effectively treat all these symptoms would be ideal. Converging data suggest that pregnenolone is a promising pharmacological agent for treating multiple psychiatric symptoms and functional impairment. The investigators thus propose to conduct a clinical trial of pregnenolone in Veterans with anxiety and depression symptoms. Pregnenolone has minimal side effects, and the prior research demonstrates that pregnenolone is well-tolerated by Veterans. Treatment with pregnenolone could thus be an efficacious new therapeutic for Veterans experiencing depression, anxiety, poor sleep quality and chronic pain conditions.

Research Team

JC

Jennifer C Naylor, PhD

Principal Investigator

Durham VA Medical Center, Durham, NC

CE

Christine E Marx, MD MA

Principal Investigator

Durham VA Medical Center, Durham, NC

Eligibility Criteria

This trial is for veterans experiencing symptoms of anxiety and depression, who may also be dealing with poor sleep quality and chronic pain. To participate, they should not have any conditions that would exclude them from the study as per the trial's specific criteria.

Inclusion Criteria

I am using or will use a non-hormonal birth control method or cannot become pregnant.
I don't expect to change my psychiatric meds during the study.
Veterans enrolled for care at the Durham VAHCS
See 2 more

Exclusion Criteria

I do not have a serious illness like a stroke or cancer (prostate, uterine, breast) that is currently unstable.
Current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern
I don't have health issues that would make taking PREG unsafe.
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Placebo Lead-in

Participants receive placebo for 2 weeks before randomization

2 weeks

Treatment

Participants receive either pregnenolone or placebo for 8 weeks with flexible dosing

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Pregnenolone
Trial Overview The clinical trial is testing pregnenolone, a medication thought to help with psychiatric symptoms and improve overall function in those suffering from anxiety and depression. Participants will either receive pregnenolone or a placebo (a substance with no active drug).
Participant Groups
2Treatment groups
Active Control
Placebo Group
Group I: PregnenoloneActive Control1 Intervention
Pregnenolone 250 mg BID x 14 DAYS, followed by Pregnenolone 500 mg BID x 14 DAYS, followed by Pregnenolone 1000 mg BID x thereafter for the remainder of the 8-week trial.
Group II: PlaceboPlacebo Group1 Intervention
Same as active comparator, except placebo dispensed

Find a Clinic Near You

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials
1,691
Recruited
3,759,000+

Findings from Research

In a study with 17 volunteers, pregnenolone was found to be well-tolerated but did not significantly affect mood, memory, or sleep quality over a 4-week period.
In a follow-up study with 11 participants, those pre-treated with pregnenolone experienced significantly less sedation from diazepam, suggesting that pregnenolone may counteract some effects of benzodiazepines, indicating a potential for enhancing arousal.
Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation.Meieran, SE., Reus, VI., Webster, R., et al.[2019]
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.
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 study of 70 participants with bipolar disorder or major depressive disorder and a history of substance abuse, pregnenolone showed a statistically significant reduction in depression symptoms compared to placebo after 8 weeks, indicating its potential efficacy in mood improvement.
Pregnenolone was found to be safe and well tolerated, but it did not demonstrate significant effects on cognitive function, suggesting that its benefits may be more focused on mood rather than cognitive deficits in this population.
Pregnenolone for cognition and mood in dual diagnosis patients.Osuji, IJ., Vera-Bolaños, E., Carmody, TJ., et al.[2013]

References

Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. [2019]
Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder. [2021]
Pregnenolone for cognition and mood in dual diagnosis patients. [2013]
Plasma pregnenolone levels in cynomolgus monkeys following pharmacological challenges of the hypothalamic-pituitary-adrenal axis. [2013]
Effects of cytochrome P450 inhibitors and of steroid hormones on the formation of 7-hydroxylated metabolites of pregnenolone in mouse brain microsomes. [2019]
Synthesis of 3beta, 7alpha, 11alpha-trihydroxy-pregn-21-benzylidene-5-en-20-one derivatives and their cytotoxic activities. [2013]
Pregnenolone and pregnenolone sulfate, alone and with ethanol, in mice on the plus-maze. [2019]
Effect of the position of the cyano-group of cyanopregnenolones on their drug metabolic inducing activity. [2018]
The Knoevenagel reactions of pregnenolone with cyanomethylene reagents: synthesis of thiophene, thieno[2,3-b]pyridine, thieno[3,2-d]isoxazole derivatives of pregnenolone and their in vitro cytotoxicity towards tumor and normal cell lines. [2013]
A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. [2021]
Microtubule associated protein 2 in bipolar depression: Impact of pregnenolone. [2022]
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