Prazosin for Post-Traumatic Stress Disorder

(PREDICT Trial)

Overseen By Rebecca C Hendrickson, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: VA Office of Research and Development

Must not be taking: Prazosin, Doxazosin, Clonidine, others

Disqualifiers: Schizophrenia, Bipolar I, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests prazosin, a medication, to determine if it can reduce symptoms in people with PTSD. Researchers are also investigating whether simple tests, such as monitoring blood pressure changes and eye reactions, can predict who will benefit from prazosin. Participants will alternate between taking prazosin and a placebo to compare effects. This trial suits veterans with PTSD who are not experiencing severe psychiatric issues or certain medical conditions. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for PTSD.

Will I have to stop taking my current medications?

You may need to stop taking certain medications like prazosin, doxazosin, clonidine, guanfacine, trazodone, and nonbenzodiazepine hypnotics at least 7 days before starting the trial. Some medications like avanafil, sildenafil, tadalafil, and vardenafil are not allowed during the dose titration period but can be used at half the usual dose afterward. It's best to discuss your current medications with the study team to see if any changes are needed.

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

Research has shown that prazosin may help alleviate PTSD symptoms such as nightmares and trouble sleeping. One review found that prazosin was more effective than a placebo in reducing PTSD-related nightmares.

While the FDA has not specifically approved prazosin for PTSD, its use for other health issues suggests it can be safe when prescribed carefully. Most people tolerate prazosin well, though some may experience mild side effects like dizziness or headaches. Participants should discuss any concerns with the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about prazosin for PTSD because it offers a different approach compared to standard treatments like SSRIs and benzodiazepines. Unlike these common medications, prazosin targets the body's response to stress by blocking certain receptors involved in the stress response, potentially reducing nightmares and improving sleep quality. This unique mechanism could provide relief for symptoms that other treatments don't fully address, making it a promising option for those who haven't found success with existing therapies.

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

Research shows that prazosin can help with PTSD symptoms, particularly nightmares and sleep issues. Studies have found that prazosin often reduces bad dreams and improves sleep quality for many people with PTSD. Some also feel less jumpy or easily startled. However, not all studies agree; one study found that prazosin didn't help military veterans with long-term PTSD as much. In this trial, participants will experience different phases, including periods of active treatment with prazosin and placebo. Overall, prazosin seems promising for some, particularly those with sleep-related PTSD symptoms. ^{1 5 6 7 8}

Who Is on the Research Team?

Rebecca C. Hendrickson, MD PhD

Principal Investigator

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Are You a Good Fit for This Trial?

This trial is for U.S. veterans with PTSD who can take prazosin, are not pregnant or breastfeeding, and don't have severe psychiatric conditions like schizophrenia or bipolar type I. Participants should not be in immediate danger to themselves or others and must agree to use birth control if applicable.

Inclusion Criteria

Veteran of the U.S. Armed Forces

I am a woman who can become pregnant and agree to use birth control or abstain from sex during the study.

I have been diagnosed with PTSD.

Exclusion Criteria

I do not have a major psychiatric or neurocognitive disorder like schizophrenia or Alzheimer's.

I haven't taken certain blood pressure or sleep medications in the last week and am willing to avoid them during the study.

Severe psychiatric instability or severe situational life crises, including evidence of being actively suicidal or homicidal, or any behavior which poses an immediate danger to participant or others. Note: Nonsuicidal depression comorbid with PTSD will not be exclusionary. Participants may continue in any concurrent psychotherapy or pharmacotherapy in which they are participating, other than pharmacotherapeutic agents specifically listed above. Participants with active suicidal ideation or with depression severe enough to require psychiatric hospitalization will be excluded.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants receive 8 weeks of active treatment with prazosin

8 weeks

Regular visits for monitoring

Blinded Discontinuation

Participants undergo a 4-week period where treatment may switch from prazosin to placebo

4 weeks

Regular visits for monitoring

Randomized Treatment

Participants are randomized to either 4 weeks of prazosin followed by 4 weeks of placebo, or vice versa

8 weeks

Regular visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Prazosin

Trial Overview The study tests whether blood pressure response upon standing and eye reaction to light can predict the effectiveness of prazosin for PTSD treatment. It also examines how trauma exposure affects stress-response regulation in the body.

How Is the Trial Designed?

Group I: Open label, blinded discontinuation, prazosin, placebo Experimental Treatment 2 Interventions

All participants in this study will begin with 8 weeks of active treatment (prazosin), followed by a 4 week "blinded discontinuation" block where they will take a capsule that will start out as active treatment (prazosin), but will at some point change to placebo. Following these phases of the study, participants will be randomized to two arms. In this first arm, participants will spend 4 weeks on active treatment (prazosin), followed by 4 weeks on placebo.

Group II: Open label, blinded discontinuation, placebo, prazosin Experimental Treatment 2 Interventions

All participants in this study will begin with 8 weeks of active treatment (prazosin), followed by a 4 week "blinded discontinuation" block where they will take a capsule that will start out as active treatment (prazosin), but will at some point change to placebo. Following these phases of the study, participants will be randomized to two arms. In this second arm, participants will spend 4 weeks on placebo, followed by 4 weeks on active treatment (prazosin).

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

Approved in United States as Minipress for:

• Hypertension
• Benign prostatic hypertrophy
• Posttraumatic stress disorder (PTSD) nightmares and hyperarousal symptoms

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8169333/

Using Prazosin to Treat Posttraumatic Stress Disorder and ... Prazosin was significantly more effective than placebo in reducing distressing dreams in PTSD patients, although our results should be interpreted with caution ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27828694/

Efficacy of Prazosin in Posttraumatic Stress Disorder This study suggests that prazosin improves nightmares and overall PTSD symptoms including hyperarousal, sleep disturbances, total sleep time, and sleep quality.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0278584625000077

Factors impacting prazosin efficacy for nightmares and ... Prazosin effectively reduces insomnia and nightmares in PTSD patients. Benzodiazepine co-administration seems to enhance prazosin's efficacy.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1507598

Trial of Prazosin for Post-Traumatic Stress Disorder in ... In this trial involving military veterans who had chronic PTSD, prazosin did not alleviate distressing dreams or improve sleep quality.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00990106

Augmentation Trial of Prazosin for Post-Traumatic Stress ... The purpose of this study is to determine whether prazosin will: reduce the incidence of nightmares and sleep disturbance; increase functioning and sense of ...

6. mayoclinic.org mayoclinic.org/diseases-conditions/post-traumatic-stress-disorder/diagnosis-treatment/drc-20355973

Post-traumatic stress disorder (PTSD) - Diagnosis and ... While the FDA has not approved this procedure to treat PTSD , studies have shown promising results. Prazosin. Prazosin (Minipress) is usually ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK555959/

Prazosin - StatPearls - NCBI Bookshelf - NIH Prazosin may reduce PTSD-associated nightmares. A systematic review by Kung et al. suggests that there is a benefit as compared to placebo in ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1389945724002478

Pharmacotherapy for sleep disturbances in post-traumatic ... Prazosin may be effective in treating insomnia, nightmares and improving sleep quality. Mirtazapine, benzodiazepines and z-drugs lack evidence and may be ...