Brexanolone for PTSD

Overseen By MacKenzie R Peltier, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: Anxiolytics, Antidepressants, Opioids, Benzodiazepines

Disqualifiers: Schizophrenia, Bipolar, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the safety and feasibility of using brexanolone, given through an IV, for people with both PTSD and AUD. The medication aims to balance brain chemicals to improve mood and reduce stress.

Will I have to stop taking my current medications?

The trial requires that participants stop using psychoactive drugs, including anxiolytics (anti-anxiety medications) and antidepressants, for at least 30 days before joining. It also excludes those taking opioids or other central nervous system depressants like benzodiazepines.

What data supports the effectiveness of the drug Brexanolone for PTSD?

Brexanolone is effective for postpartum depression (PPD), significantly reducing depression scores in women with moderate to severe PPD. However, there is no direct evidence supporting its effectiveness for PTSD, and a similar drug, ganaxolone, did not show significant benefits for PTSD in a clinical trial. ^{1 2 3 4 5}

Is Brexanolone safe for human use?

Brexanolone, also known as Zulresso, has been approved by the FDA for the treatment of postpartum depression, indicating it has been evaluated for safety in humans. While it is generally well-tolerated, the treatment involves a lengthy infusion time and can be costly. There is no specific safety data for its use in PTSD, but its approval for postpartum depression suggests a level of safety in human use. ^{1 2 4 6 7}

How is the drug Brexanolone unique for treating PTSD?

Brexanolone is unique because it is an intravenous drug that acts as a neuroactive steroid, specifically targeting GABAA receptors in the brain, which is different from most oral medications used for PTSD. It was originally developed for postpartum depression, highlighting its novel mechanism of action compared to traditional PTSD treatments. ^{1 3 4 5 8}

Research Team

MacKenzie R Peltier, Phd

Principal Investigator

Yale University

Eligibility Criteria

This trial is for adults aged 21-55 with PTSD and AUD who drink heavily but don't have severe mental illnesses, other substance use disorders (except tobacco), or are using psychoactive drugs. Pregnant/nursing women or those not on birth control are excluded, as well as anyone with serious health issues like heart problems, liver disease, seizures, or seeking AUD treatment.

Inclusion Criteria

I have been diagnosed with PTSD in the last 6 months.

Provision of signed and dated informed consent form

I am a man who drinks more than 14 times a week and has more than 5 drinks at least once a week.

Exclusion Criteria

I have been diagnosed with schizophrenia, bipolar disorder, or another severe mental illness.

I have severe kidney disease or am taking opioids or drugs like Xanax.

I do not have any major health issues like heart problems, kidney or liver disease, seizures, or HIV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive brexanolone as a continuous IV infusion over 20 hours

1 day

1 visit (in-person)

Laboratory Session

Participants complete a laboratory session with personalized imagery and a 2-hour alcohol self-administration period

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including assessments of alcohol use, PTSD symptoms, and side effects

4 weeks

Weekly visits (virtual or in-person)

Treatment Details

Interventions

• Brexanolone

Trial Overview The study tests the safety and feasibility of Brexanolone in individuals with PTSD and AUD. It aims to see if this medication can reduce stress-induced alcohol consumption among men and women meeting specific drinking criteria related to their conditions.

Participant Groups

Group I: Brexanaolone Experimental Treatment 1 Intervention

In this single-arm study, participants will be administered brexanolone as a continuous IV infusion over 20 hours (titrated up to 90mcg/kg/hour).

Brexanolone is already approved in United States for the following indications:

Approved in United States as Zulresso for:

• Postpartum Depression

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Sage Therapeutics

Industry Sponsor

Trials

51

Recruited

11,000+

Founded

2010

Headquarters

Cambridge, USA

Known For

Brain Health Medicines

Top Products

ZURZUVAE (zuranolone), SAGE-324

Findings from Research

Brexanolone (ZULRESSO™) is an intravenously administered treatment specifically designed for postpartum depression (PPD), acting as a positive allosteric modulator of GABAA receptors, which helps enhance inhibitory neurotransmission in the brain.

Approved in March 2019, brexanolone is a formulation that combines allopregnanolone, a natural neurosteroid, with a solubilizing agent, marking a significant advancement in the treatment options available for adult women suffering from PPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexanolone: First Global Approval. Scott, LJ.[2020]

In a trial involving 112 participants, ganaxolone, a neuroactive steroid, did not show significant improvements in PTSD symptoms compared to placebo, suggesting it may not be effective at the tested doses.

The study indicated that many participants had lower than expected blood levels of ganaxolone, which could explain the lack of efficacy, highlighting the need for higher dosing and better monitoring in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of ganaxolone in posttraumatic stress disorder. Rasmusson, AM., Marx, CE., Jain, S., et al.[2018]

Brexanolone (Zulresso) is an effective new treatment for postpartum depression (PPD), showing significant reductions in depression scores compared to placebo in clinical trials, particularly at doses of 60 and 90 μg/kg/hour.

While brexanolone has promising efficacy, it carries risks of somnolence and loss of consciousness, necessitating a Risk Evaluation and Mitigation Strategies (REMS) program to ensure patient safety during its administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexanolone for Postpartum Depression: Clinical Evidence and Practical Considerations. Leader, LD., O'Connell, M., VandenBerg, A.[2020]

Zulresso (brexanolone) is the only FDA-approved treatment for postpartum depression (PPD) and works by stimulating specific GABAA receptors in the brain, but its long infusion time and high cost can be barriers to use.

The study suggests that barbiturates and pyrazolopyridines, which also target the same GABAA receptors, could be repurposed as safer and more cost-effective alternatives for treating PPD, despite concerns about dependence with barbiturates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Barbiturates and pyrazolopyridines for the treatment of postpartum depression-repurposing of two drug classes. Horwitz, AB., Rubin, RT.[2023]

A pharmacovigilance study identified 267 cases of adverse drug reactions (ADRs) associated with brexanolone, with a significant number of reports related to psychiatric and nervous system issues, indicating a need for further investigation into these effects.

Serious outcomes were reported in 11.61% of patients using brexanolone, highlighting potential safety concerns that warrant additional prospective research to clarify the drug's safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety profile of brexanolone: a pharmacovigilance analysis based on FDA Adverse Event Reporting System (FAERS). Zhang, M., Xie, W., Li, J., et al.[2023]

Researchers developed new prodrugs of brexanolone, which is a synthetic version of a natural compound that helps modulate brain receptors related to mood regulation.

These prodrugs were shown to effectively release brexanolone both in laboratory tests and in living organisms, suggesting they could provide a longer-lasting treatment option for conditions like depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design, synthesis and characterizations of prodrugs of brexanolone. Xu, L., Ma, J., Shi, L., et al.[2023]

Allopregnanolone, a neuroactive steroid, shows promise in treating various stress-related conditions like PTSD, depression, and alcohol use disorders due to its ability to interact with GABAA receptors and influence stress-related pathways.

The review emphasizes the need for more clinical studies to better understand the therapeutic potential and limitations of allopregnanolone and its precursors, pregnenolone and progesterone, in managing stress-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pleiotropic actions of allopregnanolone underlie therapeutic benefits in stress-related disease. Boero, G., Porcu, P., Morrow, AL.[2020]

ZULRESSO (Brexanolone) is an FDA-approved treatment specifically for moderate-to-severe postpartum depression, highlighting the role of neurosteroids like allopregnanolone in managing this condition.

While brexanolone shows efficacy in alleviating depressive symptoms, it remains uncertain whether its effects last beyond 30 days after treatment, indicating a need for further research to assess long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexanolone to Treat Postpartum Depression in Adult Women. Cornett, EM., Rando, L., Labbé, AM., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Brexanolone: First Global Approval. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of ganaxolone in posttraumatic stress disorder. [2018]

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

Brexanolone for Postpartum Depression: Clinical Evidence and Practical Considerations. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Barbiturates and pyrazolopyridines for the treatment of postpartum depression-repurposing of two drug classes. [2023]

5. Austria pubmed.ncbi.nlm.nih.gov

Postmarketing safety profile of brexanolone: a pharmacovigilance analysis based on FDA Adverse Event Reporting System (FAERS). [2023]

6. England pubmed.ncbi.nlm.nih.gov

Design, synthesis and characterizations of prodrugs of brexanolone. [2023]

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

Pleiotropic actions of allopregnanolone underlie therapeutic benefits in stress-related disease. [2020]

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

Brexanolone to Treat Postpartum Depression in Adult Women. [2023]