Allopregnanolone for Post-Traumatic Stress Disorder

(IV Allo PTSD Trial)

Overseen By Kristen Curran

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Opiates, Benzodiazepines, Hormone therapy, others

Disqualifiers: Substance use disorder, Bipolar, Schizophrenia, Severe TBI, others

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

Compensation: Varies

Number of Visits: 4

Duration: 3 days

96 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for post-traumatic stress disorder (PTSD) using allopregnanolone, a neurosteroid. The researchers aim to determine if this treatment can help the brain manage traumatic memories, either by aiding individuals in releasing the stress these memories cause or by preventing strong, distressing reactions. The trial involves a single intravenous dose of allopregnanolone compared to a non-active placebo. Individuals who have experienced PTSD for over three months and can abstain from alcohol and certain drugs for a few weeks might be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in PTSD treatment.

Will I have to stop taking my current medications?

You may need to stop taking certain medications if they could increase the risk of side effects or affect the study results. Regular psychotropic medications might need to be stopped 3 months before the study, and some non-psychotropic medications should be stopped for a certain period before the procedures. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that allopregnanolone has been tested in humans before, providing insights into its safety. In past trials, researchers closely monitored participants who received allopregnanolone for any safety issues. Early results suggested that the treatment was generally well-tolerated, with no reports of serious side effects directly linked to it.

Allopregnanolone affects brain signals, which may help reduce stress and anxiety. Although researchers are still studying this treatment, it has shown promise in other conditions like depression after a stroke, where it was also reported to be well-tolerated.

This study is in an early phase, meaning researchers are still learning about its safety and effectiveness for PTSD. However, its previous testing in humans is a positive indicator of its safety. Always consult a healthcare provider to understand what joining the trial might mean. ^{1 2 3 4 5}

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

Most treatments for PTSD, like SSRIs and cognitive behavioral therapy, focus on altering serotonin levels or modifying thought patterns over time. But allopregnanolone works differently, targeting the brain's GABA receptors to rapidly reduce symptoms of anxiety and stress. Researchers are excited about allopregnanolone because it could offer quick relief by directly modulating brain chemistry, providing a new approach for those who don't respond well to traditional therapies. Additionally, its use through intravenous administration allows for precise dosing and faster onset of effects, which is particularly promising for addressing acute episodes of PTSD.

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

Research shows that allopregnanolone might help treat PTSD. Allopregnanolone, a substance naturally found in the brain, is often at lower levels in people with PTSD, as studies have found. Increasing these levels may reduce anxiety and unwanted memories. It may also improve the brain's ability to process and store memories, which is crucial for healing from trauma. In this trial, some participants will receive IV allopregnanolone, while others will receive a placebo. Early research suggests that allopregnanolone can help the brain handle stressful memories more effectively, potentially offering a new way to support those with PTSD. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with PTSD. Participants should be able to undergo a three-day aversive conditioning, extinction, and testing paradigm. Specific eligibility criteria are not provided but typically include being diagnosed with PTSD and meeting certain health requirements.

Inclusion Criteria

I am a woman who must use two non-hormonal birth control methods before and after treatment.

I am between 18 and 55 years old, can have children, and speak English.

I have been diagnosed with PTSD for more than 3 months.

Exclusion Criteria

Awake resting O2 saturation < 96%

My kidney function is severely reduced.

Present an imminent risk to self or others or require clinical intervention to maintain safety

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pharmacokinetic Studies

Pharmacokinetic studies are conducted in a small group of individuals with PTSD to confirm that the selected IV Allo doses increase blood Allo levels as expected

1 week

Treatment

Participants undergo a 3-day laboratory psychophysiology paradigm with startle testing and receive either IV Allo or placebo

3 days

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with a follow-up phone session

1 week

1 visit (phone)

What Are the Treatments Tested in This Trial?

Interventions

• Allopregnanolone

Trial Overview The study tests if an IV dose of Allopregnanolone (Allo) can help the brain process traumatic memories by promoting 'extinction learning' or blocking 'reconsolidation'—two ways the brain deals with trauma during psychotherapy. It compares Allo's effects against a placebo in two sub-studies.

How Is the Trial Designed?

Group I: IV Allopregnanolone (Allo) for Extinction Retention (Expt. 1) Experimental Treatment 2 Interventions

Arm 1 of Expt. 1 includes women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV Allo immediately after completion of extinction training.

Group II: IV Allo for Reconsolidation Blockade (Expt. 2) Experimental Treatment 2 Interventions

Arm 1 of Expt. 2 will include women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV Allo immediately after reactivation of the conditioned aversive memory by exposure to one conditioned stimulus (CS+).

Group III: IV Placebo for Extinction Retention (Expt. 1) Placebo Group 2 Interventions

Arm 2 of Expt. 1 includes women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV placebo immediately after completion of extinction training.

Group IV: IV Placebo for Reconsolidation Blockade (Expt. 2) Placebo Group 2 Interventions

Arm 2 of Expt. 2 will include will include women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV placebo immediately after reactivation of the conditioned aversive memory by exposure to one conditioned stimulus (CS+).

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Citations

1. 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3880842/

Targeting neurosteroidogenesis as therapy for PTSD - PMC Thus, allopregnanolone or analogs are more advantageous than benzodiazepines because they improve anxiety, fear, and aggressiveness when benzodiazepines are ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04468360

Facilitation of Extinction Retention and Reconsolidation ... Implications: These studies may help us understand treatable factors that increase risk for chronic or treatment-resistant PTSD and PTSD-related depression.

4. ptsd.va.gov ptsd.va.gov/professional/articles/article-pdf/id48368.pdf

A randomized controlled trial of ganaxolone in posttraumatic ... Abstract Preclinical and clinical research supports a role for neuroactive steroids in the pathophysiology of posttraumatic stress disorder ...

5. withpower.com withpower.com/trial/phase-2-stress-disorders-post-traumatic-7-2025-fa925

Allopregnanolone for Post-Traumatic Stress Disorder Trial Overview The study tests if an IV dose of Allopregnanolone (Allo) can help the brain process traumatic memories by promoting 'extinction learning' or ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6584957/

Relationships between cerebrospinal fluid GABAergic ... It is therefore conceivable that a loss-of-function 5α-reductase II gene polymorphism might increase PTSD risk in men by a) compromising Allopregnanolone ...

7. mdpi.com mdpi.com/2075-1729/13/8/1731

Novel Pharmacological Targets of Post-Traumatic Stress ... In addition, recent data showing that the neurosteroid allopregnanolone, a potent GABAergic modulator, is involved in restoring the normal functioning of the ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06759558

Allopregnanolone (Zuranolone) in Post-stroke Depression The goal of this Phase II clinical trial is to learn if the oral synthetic allopreganolone analog (zuranolone) is safe to take and is well tolerated by stroke ...