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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of brexanolone, a medication for individuals with both PTSD and Alcohol Use Disorder. Researchers seek to determine if administering this treatment safely to individuals with these conditions is feasible. Participants will receive the medication through an IV over 20 hours. This trial may suit those with PTSD who meet specific drinking criteria but are not actively seeking treatment for alcohol use. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

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.

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

Research has shown that brexanolone is generally safe for people. The FDA has approved it for treating postpartum depression, confirming its safety for that use. In another study, researchers administered brexanolone to adults with PTSD (post-traumatic stress disorder) and found it safe, with no major side effects reported. Evidence so far suggests that most people can use the treatment without serious problems. However, each person's experience may vary. Always consult a healthcare provider for advice tailored to individual health needs. ^{1 2 3 4 5}

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

Most treatments for PTSD, like selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy, take weeks or even months to show effectiveness. But Brexanolone works differently, targeting the brain's GABA receptors to potentially stabilize mood rapidly. Researchers are excited about this treatment because it is administered as a continuous IV infusion, which allows for a controlled, steady delivery over 20 hours, possibly leading to quicker symptom relief. This unique approach could offer a faster-acting alternative for those struggling with PTSD.

What evidence suggests that brexanolone might be an effective treatment for PTSD?

Studies have shown that brexanolone effectively treats postpartum depression. This success suggests potential benefits for PTSD (Post-Traumatic Stress Disorder), as both conditions involve mood changes. Research indicates that neurosteroids like brexanolone can positively influence stress and fear responses. Early findings suggest that brexanolone may alter specific brain chemicals related to stress. Although brexanolone is not yet proven for PTSD, its success in similar conditions is promising. Participants in this trial will receive brexanolone as a continuous IV infusion over 20 hours to evaluate its potential effectiveness for PTSD. ^{2 5 6 7 8}

Who Is on the Research Team?

MacKenzie R Peltier, Phd

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05254405

An Open Label Pilot Study of IV Brexanolone for the ... The primary efficacy outcome measure is change in PTSD Checklist for DSM-5 (PCL-5) total score from baseline at study endpoint (i.e., Week 12/Day 90). The PCL-5 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11364262/

The Emerging Role of Neurosteroids - PubMed Central - NIH The four neurosteroids studied have shown positive outcomes in patients with conditions such as postpartum depression, post-traumatic stress ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0278584624002367

Allopregnanolone and intrusive memories: A potential ... Allopregnanolone may have a role in stress, fear and intrusive memories. Allopregnanolone potentially influences intrusive memory development.

4. withpower.com withpower.com/trial/phase-4-stress-disorders-traumatic-2-2022-355c7

Brexanolone for Post-Traumatic Stress Disorder Brexanolone (Zulresso) is an effective new treatment for postpartum depression ... Serious outcomes were reported in 11.61% of patients using brexanolone ...

5. thelancet.com thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00038-5/fulltext

Brexanolone therapeutics in post-partum depression ... The data show that brexanolone infusion alters multiple neuroactive steroid levels, inhibits production of inflammatory mediators TNF-α and IL-6 ...

6. samhsa.gov samhsa.gov/

Home | SAMHSA - Substance Abuse and Mental Health ... SAMHSA leads efforts to advance behavioral health across the U.S., offering resources for mental health, substance use, and community well-being.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10491550/

Safety of Brexanolone in Adults with Postpartum Depression Brexanolone is currently the only medication approved by the US FDA for the treatment of postpartum depression (PPD) in patients ≥15 years.

8. womensmentalhealth.org womensmentalhealth.org/posts/tag/brexanolone/

brexanolone As of October 2023, the Neurosteroid Intervention for Menopausal and Perimenopausal Depression is no longer recruiting participants.