Glecaprevir/Pibrentasvir for Post-traumatic Stress Disorder

Study Overview
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Brief Summary
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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).

Detailed Description
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N=92 patients with posttraumatic stress disorder (PTSD) will be enrolled into a double-blind randomized placebo-controlled trial to further investigate glecaprevir/pibrentasvir (GLE/PIB), a direct acting antiviral (DAA) that has been associated with PTSD symptom improvement when prescribed for the treatment of chronic hepatitis C viral infection (HCV). The research is intended to test the efficacy of GLE/PIB for PTSD symptom improvement in the absence of HCV. Primary Aims: Aim 1: Determine the efficacy of GLE/PIB for PTSD symptom improvement. Aim 2: Determine the efficacy of GLE/PIB for functioning improvement among patients with PTSD. Aim 3: Assess the safety and tolerability of GLE/PIB treatment for patients with PTSD in the absence of HCV.

Official Title
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Randomized Controlled Trial of Glecaprevir/Pibrentasvir for the Treatment of Post-traumatic Stress Disorder

Conditions
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PTSD

Intervention / Treatment
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* Drug: Glecaprevir/pibrentasvir
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 19-70 years Weight ≥ 45 kg Diagnosed with PTSD as determined by the CAPS-5 within seven days of enrollment Eligible for Veterans Affairs healthcare If person with childbearing potential, use of acceptable method of birth control (i.e., effective contraceptives, abstinence) is required. Able to read, understand, and sign the informed consent document. Exclusion (unable to participate) Criteria: Pregnant or lactating person Moderate or severe hepatic impairment (Child-Pugh B or C) History of prior hepatic decompensation Current use of drugs listed as having significant drug interactions on prescribing label Advanced liver disease Current or prior hepatitis B infection Prior clinical use of GLE/PIB or HCV NS5A inhibitor AND NS3/4A protease inhibitor Current HCV infection Current psychosis or mania Significant suicidal ideation Unstable medical conditions Current severe alcohol or substance use disorder (excluding nicotine) Evidence-based PTSD psychotherapy changes in the past two months Evidence-based PTSD medication changes in the past two months

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Blinded placebo-controlled randomized trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Drug<br>Glecaprevir 100 mg/Pibrentasvir 40 mg, 3 oral tablets once daily for 8 weeks. | Drug: Glecaprevir/pibrentasvir<br>* Direct-acting antiviral, Food & Drug Administration (FDA) approved for the treatment of hepatitis C viral infection<br>* Other names: Mavyret;|
| Placebo Comparator: Placebo<br>Placebo, 3 oral tablets once daily for 8 weeks. | Other: Placebo<br>* Compounded, inactive pill equal in appearance to active study drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Administered Post-Traumatic Stress Disorder Scale version 5 (CAPS-5) | Queries the frequency and intensity of symptoms of post-traumatic stress disorder (PTSD). The score ranges from 0-80 with a higher score indicating worse symptoms. It is considered the gold standard for diagnosis and symptoms assessment in PTSD clinical studies. | Change from Baseline CAPS score at 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| World Health Organization Disability Assessment Schedule, version 2.0 (WHODAS) | A 36 item self-report instrument that assesses disability and function across six domains: communicating, getting around, self-care, getting along with people, life activities, and participation in society. The WHODAS has been used as an outcome of function and disability across many disorders and is commonly used in mental health treatment trials. The total score ranges from 0-180 with a higher score indicating worse functioning. | Change from Baseline WHODAS score at 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PTSD, Antiviral, Hepatitis C