Pregnenolone for Chronic Traumatic Brain Injury

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Chris Marx, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Christine Marx, MD

Must not be taking: Benzodiazepines, Opioids, Hormonal supplements, others

Disqualifiers: Seizures, Stroke, Bipolar, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing whether pregnenolone can help improve mental and physical health in veterans with long-term brain injuries. Participants will take pregnenolone daily for a period of time. The study aims to see if pregnenolone is effective in improving health outcomes and to find the best safe dose.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications if they are for stable and well-controlled conditions, like hypertension. However, you cannot change psychiatric or pain medications during the study or in the two weeks before joining. Some medications, like prednisone, are not allowed as they could affect the study results.

What evidence supports the effectiveness of pregnenolone as a drug for chronic traumatic brain injury?

Pregnenolone has shown potential in reducing sedation effects when used with diazepam, a medication affecting the brain, and has been studied for its role in modulating alcohol intake in animal models. However, its direct effectiveness for chronic traumatic brain injury is not clearly established in the provided research. ^{1 2 3 4 5}

Is pregnenolone generally safe for humans?

Pregnenolone has been generally well-tolerated in studies with humans, showing no significant negative effects on mood, memory, sleep quality, or well-being. It appeared safe and well-tolerated in patients with mood and substance-use disorders, although it may increase certain risks in specific conditions, such as facilitating neuronal damage in animal models exposed to hypoxia. ^{2 4 5 6 7}

How is the drug pregnenolone unique for treating chronic traumatic brain injury?

Pregnenolone is unique because it is a neurosteroid that can modulate brain receptors like GABA(A), potentially affecting mood and cognition, which might be beneficial for brain injury recovery. Unlike other treatments, it has been studied for its effects on mood and cognitive functions in various conditions, suggesting it might offer novel benefits for brain injury patients. ^{2 4 5 6 7}

Research Team

Chris Marx, MD

Principal Investigator

Duke University

Eligibility Criteria

This trial is for OEF/OIF/OND-era U.S. Military Veterans aged 21-65 with a history of mild TBI since 2001, who can read English and consent to the study. They must not plan to change psychiatric or pain meds during the study, have no recent psychotropic interventions, and if female and able to become pregnant, must use birth control.

Inclusion Criteria

Ability to read/understand English and to participate fully in the informed consent process

History of mild TBI since 2001 and service in the U.S. Military since 9/11/01 (OEF/OIF/OND era) adhering to the WHO diagnostic definition of mild TBI

No changes in psychotropic or behavioral interventions during the study or in the 2 weeks prior to study enrollment

Exclusion Criteria

Participants with current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern

Participants who report a history of seizures, a history of stroke, a history of prostate cancer (or any other cancer other than non-melanoma skin cancer), a history of myocardial infarction, the presence of congestive heart failure, or any other serious health condition that would likely preclude safe study participation in the medical opinion of the PI or in consultation with the participant's PCP/other health care provider

Substance use disorder (DSM-5), other than nicotine use disorder

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either pregnenolone or placebo daily at home over an 8-week period

8 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 weeks

Treatment Details

Interventions

• Placebo (Other)
• Pregnenolone (Corticosteroid)

Trial Overview The trial tests whether pregnenolone improves psychological health, physical function, cognition, PTSD symptoms, and pain in veterans with chronic TBI compared to a placebo over eight weeks. It also examines biological effects of pregnenolone and its optimal safe dose.

Participant Groups

Group I: Pregnenolone Active Control 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Durham VA Health Care System Durham, NC

Duke University School of Medicine Durham, NC

Who Is Running the Clinical Trial?

Christine Marx, MD

Lead Sponsor

Trials

1

Patients Recruited

110+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnenolone and ganaxolone reduce operant ethanol self-administration in alcohol-preferring p rats. Besheer, J., Lindsay, TG., O'Buckley, TK., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Meieran, SE., Reus, VI., Webster, R., et al.[2019]

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of pregnenolone effects on alcohol intake and preference in male alcohol preferring (P) rats. Rezvani, AH., Levin, ED.[2014]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential effect of dehydroepiandrosterone and its steroid precursor pregnenolone against the behavioural deficits in CO-exposed mice. Maurice, T., Phan, V., Sandillon, F., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnenolone for cognition and mood in dual diagnosis patients. Osuji, IJ., Vera-Bolaños, E., Carmody, TJ., et al.[2013]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pregnenolone and ganaxolone reduce operant ethanol self-administration in alcohol-preferring p rats. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. [2019]

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]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Assessment of pregnenolone effects on alcohol intake and preference in male alcohol preferring (P) rats. [2014]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Differential effect of dehydroepiandrosterone and its steroid precursor pregnenolone against the behavioural deficits in CO-exposed mice. [2019]

6. Ireland pubmed.ncbi.nlm.nih.gov

Pregnenolone for cognition and mood in dual diagnosis patients. [2013]

7. 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]