Gabapentin to Reduce Alcohol and Improve Viral Load Suppression

HIV Clinical Trial

— GRAIL  

Official title:

Gabapentin to Reduce Alcohol and Improve Viral Load Suppression - Promoting "Treatment as Prevention"

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05443555
• Other study ID #: H-42904
• Secondary ID: R01AA030460
• Status: Recruiting
• Phase: Phase 2
• Start date: November 20, 2023
• Est. completion date: May 2027

Study information

• Verified date: May 2024
• Source: Boston Medical Center
• Contact: Jeffrey Samet, MD MA MPH
• Phone: (617) 414-7288
• Email: jsamet[@]bu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

GRAIL is a Randomized Controlled Trial (RCT) among 300 HIV-positive persons with heavy alcohol consumption (by NIAAA definition) who have had detectable HIV viral load (HVL) at least 6 months after their HIV diagnosis. This trial aims to test the efficacy of gabapentin versus placebo to achieve undetectable HVL and assess the impact of gabapentin compared to placebo on alcohol consumption, pain severity, ART adherence, and engagement in HIV care. HIV viral load will be assessed at 3 (primary), 6 and 12 months via laboratory test. Eligible participants will be randomly assigned into one of two study arms: 1) gabapentin (1800mg/day target dose) for 3 months vs. 2) placebo for 3 months. All participants will receive evidence-based counseling for alcohol and either an active medication or placebo.

Description:

Ending the HIV epidemic requires achieving HIV viral load (HVL) suppression (i.e., undetectable viral load) for key populations. Unhealthy alcohol use by people with HIV (PWH) is a barrier to reaching HVL suppression at multiple stages of the HIV care cascade. Alcohol use is common among PWH and results in lower antiretroviral therapy (ART) adherence and HVL suppression, mitigating the effectiveness of Treatment as Prevention (TasP), a key strategy for preventing HIV transmission. Treating alcohol use is therefore a mechanism to support PWH with unhealthy alcohol use along the HIV care cascade (e.g., ART initiation, retention in care, medication adherence, and HVL suppression).

The investigators propose the Gabapentin to Reduce Alcohol and Improve Viral Load Suppression (GRAIL) trial to test the efficacy of gabapentin vs. placebo on achieving viral load suppression among PWH. The study population will be heavy drinkers with a detectable viral load at least 6 months after their HIV diagnosis. The rationale for this trial is that effective pharmacological alcohol treatment will help PWH with heavy alcohol use who have a known HIV diagnosis for at least 6 months to successfully engage in HIV care. The overarching strategy to achieve TasP is that gabapentin will reduce heavy alcohol use, thereby increasing HIV care engagement, ART use and adherence while decreasing pain, all of which ultimately promote viral load suppression.

GRAIL is a randomized, double-blinded, placebo-controlled clinical trial that will evaluate the efficacy of gabapentin in promoting HVL suppression via reducing alcohol use among PWH but not virally suppressed (i.e., The study population will be heavy drinkers with a detectable viral load for 6 months or more after their HIV diagnosis). Participants will be randomized 1:1 to receive either gabapentin (1800mg/day target dose) or placebo for 3 months; both arms will employ a brief intervention to reduce alcohol use.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: May 2027
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Having an HIV diagnosis for at least 6 months

• Current (within 2 months) detectable HIV viral load at least 6 months after HIV diagnosis

• Positive EtG urine test

• Able and willing to comply with all study protocols and procedures

• Living within 2 hours travel time of the study site

Exclusion Criteria:

• Not fluent in English or Runyankole

• Cognitive impairment resulting in inability to provide informed consent based on research assessor (RA) assessment

• Pregnancy, planning to become pregnant in next 3 months, or breast feeding

• Taking gabapentin/pregabalin in past 30 days

• Taking any medication for alcohol use disorder

• Enrolled in another HIV research study seeking viral load suppression

• Known hypersensitivity to gabapentin

• Unstable psychiatric illness (i.e., answered yes to any of the following: past three month active hallucinations; mental health symptoms prompting a visit to the emergency department (ED) or hospital; mental health medication changes due to worsening symptoms; presence of suicidal ideations)

Related Conditions & MeSH terms

• Heavy Drinking
• HIV

Intervention

Drug:
• Gabapentin
Dosing will be titrated up over 3 weeks, starting with a daily dose of 300mg (1 capsule/day) in week 1, followed by a daily dose of 900mg (3 capsules/day) in week 2, up to a target daily dose of 1800mg (6 capsules/day) in week 3. The target dose of 1800mg per day will be sustained from weeks 3 through day 4 of week 12. Then, dose will be tapered down to 900mg in days 5-7 of week 12, and medication will be discontinued at the end of week 12.
• Placebo
Participants randomized to this group will receive a placebo medication for 3 months and will be instructed to follow the same pill regimen as the intervention arm.

Locations

Country	Name	City	State
Uganda	Mbarara Regional Referral Hospital (MRRH): Immune Suppression Syndrome HIV	Mbarara

Sponsors (2)

Lead Sponsor	Collaborator
Boston Medical Center	National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of heavy drinking days in the past month	Assessed by self-report using the Timeline Followback method	3, 6, and 12 months post randomization
Other	Number of participants with heavy alcohol consumption defined as Phosphatidylethanol (PEth) =50 ng/mL	Assessed by study test	3, 6, and 12 months post randomization
Other	Adherence to ART	Measured by participants' drawing a line on a Visual Analog Scale, which ranges from 0 to 100. =80% indicates adherence to ART.	3, 6, and 12 months post randomization
Other	Percentage of ART pills taken	Assessed by self-report	3, 6, and 12 months post randomization
Other	Change in pain severity from baseline to follow-up	Assessed by Brief Pain Inventory with a range of scores from 0 (none) to 10 (high) where lower scores are favorable.	3, 6, and 12 months post randomization
Other	Engagement in HIV care	Defined as = 1 HIV visit in the past 3 months assessed by medical record review	3, 6, and 12 months post randomization
Primary	Number of participants with undetectable HIV viral load	Assessed by study test	3 months post randomization
Secondary	Number of participants with undetectable HIV viral load	Assessed by study test	6 months post randomization
Secondary	Number of participants with undetectable HIV viral load	Assessed by study test	12 months post randomization