Brexanolone for Post-Traumatic Stress Disorder

Overseen By Madeline Sheehan

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Donald Jeffrey Newport

Must not be taking: Benzodiazepines, CNS depressants

Disqualifiers: Pregnancy, Renal failure, Bipolar, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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: 6

Duration: 30 hours

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if brexanolone, administered through a 24-hour IV infusion, can reduce PTSD symptoms in women who have experienced non-military trauma. Researchers are also assessing the treatment's safety and its effects on depression and daily functioning. Women diagnosed with PTSD who face significant daily challenges due to their symptoms might be suitable candidates. As a Phase 4 trial, this study involves an FDA-approved treatment and focuses on understanding its benefits for a broader patient population.

Will I have to stop taking my current medications?

The trial requires that if you are taking psychotropic medications, they must be at a stable dose for at least 14 days before the study and until 72 hours after the study drug infusion. You cannot start any new antidepressant or anti-anxiety medications until after the 72-hour assessments are completed.

What is the safety track record for brexanolone?

Research shows that brexanolone, also known as Zulresso, is generally safe for adults. Studies have found it effective for treating conditions like postpartum depression. After the drug's approval, data from users indicated that side effects are usually mild to moderate, with serious side effects being rare.

In clinical trials, most participants reported feeling sleepy or dizzy, but these symptoms typically resolved. Safety measures, such as monitoring vital signs and assessing sleepiness and mood, ensure brexanolone's safe use. Since it is already approved for other conditions, confidence in its safety remains high. However, discussing any concerns with the healthcare team before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike standard treatments for PTSD that often involve therapy or oral medications like SSRIs and SNRIs, brexanolone is administered intravenously over a continuous 60-hour period. This unique delivery method allows for direct and controlled dosing in a healthcare setting. Researchers are particularly excited about brexanolone because it targets the brain's GABA system, potentially offering faster symptom relief compared to traditional options. This novel approach could provide a new avenue for managing PTSD symptoms more effectively and quickly.

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

Research has shown that brexanolone, also known as Zulresso, effectively treats postpartum depression by significantly lowering depression scores compared to a placebo. This success has sparked interest in its use for other conditions like PTSD. Brexanolone increases levels of allopregnanolone, a brain chemical often low in people with PTSD. Studies have found that low levels of this chemical link to memory problems in PTSD, suggesting that brexanolone could help by boosting these levels. While primarily used for postpartum depression, the mechanism of brexanolone suggests it could also alleviate PTSD symptoms. Participants in this trial will receive an open-label infusion of brexanolone to explore its potential benefits for PTSD. ^{1 6 7 8 9}

Who Is on the Research Team?

Donald J Newport, MD

Principal Investigator

University of Texas at Austin/ Dell Medical School

Are You a Good Fit for This Trial?

This trial is for premenopausal women aged 18-50 with PTSD from civilian trauma, fluent in the test language, and in good health. Participants must not be pregnant or breastfeeding, have a stable psychotropic medication dose if any, and agree to use effective birth control during the study.

Inclusion Criteria

I have been diagnosed with PTSD from a civilian trauma.

Subject has signed an ICF prior to any study-specific procedures being performed

Subject agrees to adhere to the study requirements

Exclusion Criteria

History of an active substance use disorder in the 6 months prior to screening

I am not starting any new mental health medications within 2 weeks of screening.

I have a history of seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive continuous IV infusion of brexanolone over a 24-hour period

30 hours

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

5 visits (telemedicine)

What Are the Treatments Tested in This Trial?

Interventions

• Brexanolone Injection [Zulresso]

Trial Overview The study tests Brexanolone Injection [Zulresso], given intravenously over 60 hours to see if it reduces PTSD symptoms severity based on PCL-5 scores and improves sleepiness and depression scales without causing significant side effects.

How Is the Trial Designed?

Group I: Open-Label Infusion of Brexanolone Experimental Treatment 1 Intervention

This is a single arm pilot study of open label brexanolone delivered intravenously over a continuous 60-hour period. Infusions will be administered in a certified healthcare setting in accordance with the Zulresso™ dosing, administration and safety guidelines.

Brexanolone Injection [Zulresso] 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?

Donald Jeffrey Newport

Lead Sponsor

Trials

1

Recruited

20+

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]

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]

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]

Citations

1. 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 ...

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

Allopregnanolone and intrusive memories: A potential ... As allopregnanolone is documented to be decreased in PTSD populations (Rasmusson et al., 2006), it may be suggested that allopregnanolone decreases memory and ...

3. 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 (PPD), showing significant reductions in depression scores compared to placebo in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8293057/

Treating Postpartum Depression: What Do We Know about ... Brexanolone is being hailed as a 'breakthrough' medication for the treatment of PPD [50]. As highlighted in this review, the positive outcomes ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02942004

NCT02942004 | A Study to Evaluate Efficacy and Safety of ... The purpose of this study was to determine if SAGE-547 Injection infused intravenously at up to 90 micrograms per kilogram per hour (μg/kg/h) for 60 hours ...

6. womensmentalhealth.org womensmentalhealth.org/posts/post-marketing-safety-data-for-brexanolone-zulresso/

Post-Marketing Safety Data for Brexanolone (Zulresso) A recent study has examined postmarketing surveillance data to better estimate the frequency and severity of adverse events reported in adults treated with ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05254405

An Open Label Pilot Study of IV Brexanolone for the ... Safety and tolerability will be assessed throughout the study by ascertainment of adverse events (AEs) including serious AEs throughout the study. Official ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10455314/

Novel Pharmacological Targets of Post-Traumatic Stress ... An Open Label Pilot Study of IV Brexanolone for the Treatment of Post-Traumatic Stress Disorder ... data suggest safety and efficacy in attenuating elevated ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178123004006

The efficacy and safety of some new GABAkines for ... This study aims to systematically review and examine the efficacy and safety of zuranolone or brexanolone for treatment of depression.