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

Trial Summary

What is the purpose of this trial?

A double-blind randomized placebo-controlled trial to further investigate glecaprevir/pibrentasvir (GLE/PIB), a direct acting antiviral (DAA) that has been associated with posttraumatic stress disorder (PTSD) symptom improvement when prescribed for the treatment of chronic hepatitis C viral infection (HCV).

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.

What data supports the effectiveness of the drug Glecaprevir/Pibrentasvir for treating PTSD?

A study found that Glecaprevir/Pibrentasvir, a drug effective for hepatitis C, was associated with improvement in PTSD symptoms among veterans, showing better results compared to another hepatitis C treatment, ledipasvir/sofosbuvir. ^{1 2 3 4 5}

Is Glecaprevir/Pibrentasvir safe for humans?

Glecaprevir/Pibrentasvir has been used safely in humans for treating hepatitis C virus infection, with most patients being cured of the virus. While the study focused on its effectiveness for PTSD, it suggests that the medication is generally safe for human use. ^{1 2 5 6 7}

How does the drug glecaprevir/pibrentasvir differ from other treatments for PTSD?

Glecaprevir/pibrentasvir is unique because it is a direct-acting antiviral originally used for hepatitis C, but it has shown potential in improving PTSD symptoms, unlike traditional PTSD treatments which primarily involve antidepressants and psychotherapy. ^{1 5 6 8 9}

Research Team

Bradley V Watts, MD, MPH

Principal Investigator

US Department of Veterans Affairs

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Direct-Acting Antivirals for Posttraumatic Stress Disorder in Veterans Affairs Patients With Hepatitis C Virus Infection. [2023]

2. United States 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Comparing Medications for DSM-5 PTSD in Routine VA Practice. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Changes in Alcohol Consumption following Direct-Acting Antiviral Treatment for Hepatitis C in VA Patients with Comorbid Alcohol Use Disorder and PTSD. [2023]

5. England pubmed.ncbi.nlm.nih.gov

A pilot randomized placebo-controlled trial of adjunctive aripiprazole for chronic PTSD in US military Veterans resistant to antidepressant treatment. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Aripiprazole for Post-traumatic Stress Disorder: A Systematic Review. [2018]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Pharmacological Management of Nightmares Associated with Posttraumatic Stress Disorder. [2022]

8. Brazil pubmed.ncbi.nlm.nih.gov

Aripiprazole in the treatment of posttraumatic stress disorder: an open-label trial. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Treatment-resistant posttraumatic stress disorder: strategies for intervention. [2019]