Glecaprevir/Pibrentasvir for Post-Traumatic Stress Disorder

Overseen By Emily Colon, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: White River Junction Veterans Affairs Medical Center

Must not be taking: HCV NS5A inhibitors

Disqualifiers: Hepatic impairment, Hepatitis B, Psychosis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

92 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the medication glecaprevir/pibrentasvir, already used for hepatitis C, can reduce PTSD symptoms. Participants will receive either the medication or a placebo (a sugar pill with no active ingredient) to compare effects. The trial aims to determine if this drug can offer new PTSD treatment options. Individuals diagnosed with PTSD and eligible for Veterans Affairs healthcare might be suitable for this study. As a Phase 2, Phase 3 trial, it focuses on assessing the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking PTSD treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using drugs that have significant interactions with the trial medication. Also, you should not have changed your PTSD medications in the past two months.

Is there any evidence suggesting that glecaprevir/pibrentasvir is likely to be safe for humans?

Research has shown that glecaprevir/pibrentasvir (GLE/PIB) is generally safe for people. It is already used to treat hepatitis C and is usually well-tolerated. In studies, most side effects were mild, such as headaches and fatigue, while serious side effects were rare. As this treatment is in the later stages of testing for a new use, strong evidence supports its safety. Prospective trial participants should know that the treatment has a good safety record. ^{1 2 3 4 5}

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

Unlike the standard treatments for PTSD, which often include psychotherapy and medications like SSRIs and SNRIs, Glecaprevir/Pibrentasvir offers a novel approach by utilizing antiviral agents. These drugs, typically used to treat hepatitis C, work by targeting specific proteins involved in viral replication, which might also have a role in the underlying biology of PTSD. Researchers are excited about this treatment because it explores a completely different mechanism of action, which could open new pathways for addressing PTSD symptoms more effectively. If successful, this could lead to faster and potentially more effective relief for patients.

What evidence suggests that glecaprevir/pibrentasvir might be an effective treatment for PTSD?

Research has shown that the medication glecaprevir/pibrentasvir (GLE/PIB), typically used for hepatitis C, might also alleviate PTSD symptoms. In studies, participants taking GLE/PIB showed greater improvement in PTSD symptoms compared to those using other treatments. Specifically, they improved by 15 points on the PTSD Checklist, which measures symptom severity—a significant improvement. This trial will compare GLE/PIB to a placebo to evaluate its effectiveness in reducing PTSD symptoms, even for those without hepatitis C. This makes GLE/PIB a promising option for treating PTSD. ^{3 5 6 7 8}

Who Is on the Research Team?

Bradley V Watts, MD, MPH

Principal Investigator

US Department of Veterans Affairs

Are You a Good Fit for This Trial?

Adults aged 19-70 with PTSD, weighing at least 45 kg, eligible for Veterans Affairs healthcare can join. They must use effective birth control if applicable and be able to consent. Excluded are those with recent PTSD treatment changes, advanced liver disease, hepatitis B or current HCV infection, unstable conditions, pregnancy, severe hepatic impairment or certain drug interactions.

Inclusion Criteria

Eligible for Veterans Affairs healthcare

I have been diagnosed with PTSD recently.

My weight is at least 45 kg.

Exclusion Criteria

Significant suicidal ideation

Pregnant or lactating person

I am not taking any medications that are known to have serious interactions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Glecaprevir/Pibrentasvir or placebo, 3 oral tablets once daily for 8 weeks

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Glecaprevir/pibrentasvir

Trial Overview The trial is testing Glecaprevir/Pibrentasvir (GLE/PIB), a medication typically used for hepatitis C but may improve PTSD symptoms. Participants will either receive GLE/PIB or a placebo without knowing which one they're getting to compare the effects on PTSD.

How Is the Trial Designed?

Group I: Active Drug Active Control 1 Intervention

Glecaprevir 100 mg/Pibrentasvir 40 mg, 3 oral tablets once daily for 8 weeks.

Group II: Placebo Placebo Group 1 Intervention

Placebo, 3 oral tablets once daily for 8 weeks.

Who Is Running the Clinical Trial?

White River Junction Veterans Affairs Medical Center

Lead Sponsor

Trials

32

Recruited

17,900+

Published Research Related to This Trial

In a study of 834 VA outpatients with PTSD, venlafaxine was found to be significantly more effective than fluoxetine, paroxetine, sertraline, and topiramate in achieving remission of PTSD symptoms during the acute treatment phase.

Continuing medication during the continuation phase was associated with a lower risk of needing acute psychiatric services, highlighting the importance of ongoing treatment for managing PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing Medications for DSM-5 PTSD in Routine VA Practice. Shiner, B., Leonard, CE., Gui, J., et al.[2022]

Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine, paroxetine, and sertraline show a statistically significant but small effect in reducing PTSD symptoms compared to placebo, based on a systematic review of 115 randomized controlled trials.

Prazosin and risperidone also demonstrate small positive effects when used to augment other treatments, but no single pharmacological intervention was found to be superior to others in head-to-head comparisons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches. Hoskins, MD., Bridges, J., Sinnerton, R., et al.[2023]

Post-traumatic nightmares (PTNs) are a significant issue for individuals with PTSD, leading to distress and decreased quality of life, and effective treatment of these nightmares can improve overall PTSD symptoms and health outcomes.

While traditional medications for PTSD have limited effects on nightmares, novel agents like ramelteon, cannabinoids, and ketamine show promise, but more large randomized controlled trials are needed to confirm their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological Management of Nightmares Associated with Posttraumatic Stress Disorder. Geldenhuys, C., van den Heuvel, LL., Steyn, P., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05637879

Glecaprevir/Pibrentasvir for Post-traumatic Stress Disorder N=92 patients with posttraumatic stress disorder (PTSD) will be enrolled into a double-blind randomized placebo-controlled trial to further investigate ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9989349/

Comparative Effectiveness of Direct-Acting Antivirals for ... PTSD outcomes were superior for those receiving GLE/PIB compared with those receiving LDV/SOF, indicating that GLE/PIB may merit further investigation as a ...

3. ptsd.va.gov ptsd.va.gov/professional/articles/article-pdf/id1580991.pdf

Mining Clinical Data for Novel Posttraumatic Stress Disorder ... Improved by 15 or more points on the PTSD Checklist (compared with 7 points or less or PTSD Checklist worsening). b. Mavyret (glecaprevir/pibrentasvir), fixed- ...

4. clinicaltrial.be clinicaltrial.be/en/details/85424?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

Glecaprevir/Pibrentasvir for Post-traumatic Stress Disord... The research is intended to test the efficacy of GLE/PIB for PTSD symptom improvement in the absence of HCV.

5. cdmrp.health.mil cdmrp.health.mil/tbiphrp/research_highlights/23Watts_highlight

Glecaprevir/Pibrentasvir for the Treatment of Posttraumatic ... Glecaprevir/Pibrentasvir for the Treatment of Posttraumatic Stress Disorder. Posted September 26, 2023. Dr. Bradley V. Watts, M.D., White River ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05637879?term=AREA%5BConditionSearch%5D(PTSD%20%26%20C-PTSD)&rank=2

Glecaprevir/Pibrentasvir for Post-traumatic Stress Disorder An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37380536/

Safety of Glecaprevir/Pibrentasvir for hepatitis C in patients ... Safety of Glecaprevir/Pibrentasvir for hepatitis C in patients with posttraumatic stress disorder: A post-marketing surveillance study

8. mdpi.com mdpi.com/1999-4915/14/7/1541

Updated Data from the German Hepatitis C-Registry (DHC-R) Real-World Safety, Effectiveness, and Patient-Reported Outcomes in Patients with Chronic Hepatitis C Virus Infection Treated with Glecaprevir/Pibrentasvir: ...