St. PETERsburg Pain and Alcohol Intervention With Naltrexone and Gabapentin

NCT ID: NCT04052139

Last Updated: 2022-11-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-25
• Study Completion Date: 2021-12-15

Brief Summary

This study is a 3-arm pilot, randomized, double-blinded, placebo-controlled study of low-dose naltrexone and gabapentin versus placebo among HIV-positive persons with heavy alcohol use and chronic pain to provide estimates of their effects on 1) pain; 2) inflammation; and 3) measures of HIV control. Participants will be followed for 12 weeks. Assessments of study outcomes will be compared at week 8 (end of treatment phase).

Detailed Description

Pain is a common co-morbidity for HIV-positive patients.Prevalence studies suggest that, on average, half of all HIV-positive persons suffer pain. Chronic pain can lead to heavy alcohol use among HIV-positive persons, which may in turn be a barrier to treatment/control of HIV and contribute to spread of HIV. Thus there is an urgent need to address pain among persons with HIV. It is timely and relevant to conduct research on gabapentin, as it has emerged as one of the most commonly prescribed non-opioid medications for pain despite the fact that gabapentin is only FDA approved for "post-herpetic neuralgia" and the literature to support its use for generalized chronic pain is limited. And yet, gabapentin has demonstrated benefits for treatment of alcohol use disorder, and therefore, like naltrexone, it could have a specific role for treating patients with chronic pain and unhealthy alcohol use. This study is a 3-arm pilot, randomized, double-blinded, placebo-controlled study of low-dose naltrexone and gabapentin vs. placebo among HIV-positive persons with heavy alcohol use and chronic pain to provide estimates of their effects on 1) pain (both self-reported and experimental/cold pressor test; 2) inflammation (i.e., levels of inflammatory cytokines IL-6, IL-1β, IL-10, and TNF-α); and 3) measures of HIV control (CD4 count and viral load).

Conditions

Chronic Pain; Alcohol Use, Unspecified; HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Low-dose naltrexone

Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.

Group Type: ACTIVE_COMPARATOR

Low-dose naltrexone

Intervention Type: DRUG

4.5 mg of low dose naltrexone taken once daily for 8 weeks. In week 1, participants will take 4.5mg of naltrexone once daily. In week 2, participants will take 4.5mg of naltrexone once daily, and a placebo capsule twice daily. In weeks 3 through 7, participants will take 1 placebo capsule with 4.5 mg mg of naltrexone once daily, and 2 placebo capsules twice daily. In week 8, in days 1-4 participants will take 4.5 mg of naltrexone with a placebo capsule once daily and 2 placebo capsules twice daily; in days 5-7, participants will take 4.5 mg of naltrexone once daily, and a placebo capsule twice daily.

Gabapentin

Participants randomized to the gabapentin arm begin on a dose of 300 mg daily (300 mg qd). In week 2, participants will take 300 mg of gabapentin three times daily. In week 3 the dose will be titrated up to 1800 mg daily (300 mg+300 mg tid) will remain on the dose until week 8, when they will be tapered back down to 900 mg daily (300 mg tid). In week 8, in days 1-4 participants will take 1800 mg daily (300 mg+300 mg tid); in days 5-7, participants will take 900 mg daily (300 mg of gabapentin three times daily).

Group Type: ACTIVE_COMPARATOR

Gabapentin

Intervention Type: DRUG

Dose will begin at 300 mg daily (300 mg qd), in week 2 the dose will be titrated up to 900 mg daily (300 mg tid). In week 3, the dose will be titrated to 1800 mg daily ( 2 capsules of 300 mg tid) and participants will remain on that dose until week 8. In week 8, in days 1-4 participants will take 1800 mg daily (300 mg+300 mg tid); in days 5-7, participants will take 900 mg daily (300 mg of gabapentin three times daily).

Placebo

Participants will receive a placebo to be taken three times daily for 8 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

In week 1, participants will take 1 placebo capsule once daily. In week 2, participants will take 1 placebo capsule three times per day. In weeks 3 through 7, 2 placebo capsules three times per day. In week 8, in days 1-4 participants will take 2 placebo capsules three times per day; in days 5-7, participants will take 1 placebo capsule three times per day. The placebo medications will be composed of lactose and will not contain active ingredients.

Interventions

Low-dose naltrexone

4.5 mg of low dose naltrexone taken once daily for 8 weeks. In week 1, participants will take 4.5mg of naltrexone once daily. In week 2, participants will take 4.5mg of naltrexone once daily, and a placebo capsule twice daily. In weeks 3 through 7, participants will take 1 placebo capsule with 4.5 mg mg of naltrexone once daily, and 2 placebo capsules twice daily. In week 8, in days 1-4 participants will take 4.5 mg of naltrexone with a placebo capsule once daily and 2 placebo capsules twice daily; in days 5-7, participants will take 4.5 mg of naltrexone once daily, and a placebo capsule twice daily.

Intervention Type: DRUG

Gabapentin

Dose will begin at 300 mg daily (300 mg qd), in week 2 the dose will be titrated up to 900 mg daily (300 mg tid). In week 3, the dose will be titrated to 1800 mg daily ( 2 capsules of 300 mg tid) and participants will remain on that dose until week 8. In week 8, in days 1-4 participants will take 1800 mg daily (300 mg+300 mg tid); in days 5-7, participants will take 900 mg daily (300 mg of gabapentin three times daily).

Intervention Type: DRUG

Placebo

In week 1, participants will take 1 placebo capsule once daily. In week 2, participants will take 1 placebo capsule three times per day. In weeks 3 through 7, 2 placebo capsules three times per day. In week 8, in days 1-4 participants will take 2 placebo capsules three times per day; in days 5-7, participants will take 1 placebo capsule three times per day. The placebo medications will be composed of lactose and will not contain active ingredients.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 18 years or older
• HIV-positive
• Chronic pain (present ≥3 mo) of moderate to severe intensity
• Heavy drinking past year (Based on NIAAA criteria: > 14 standard drinks per week/ > 4 drinks in a day for men; > 7 drinks in the past week/ > 3 drinks in a day for women)
• If female, negative pregnancy test and willing to use adequate birth control
• Provision of contact information for 2 contacts to assist with follow-up
• Stable address within 100 kilometers of St. Petersburg
• Possession of a telephone (home or cell)
• Able and willing to comply with all study protocols and procedures

Exclusion Criteria

• Not fluent in Russian
• Cognitive impairment resulting in inability to provide informed consent based on research assessor (RA) assessment
• Known active TB or current febrile illness
• Breastfeeding
• Known uncontrolled psychiatric illness (such as active psychosis)
• Current suicidal ideation
• History of hypersensitivity to naltrexone, gabapentin, or naloxone
• Current use (past week) of illicit or prescribed opiates as documented by either self-report or positive urine drug test
• Unwilling to abstain from opiates during the treatment period
• Current use of neuroleptics
• History of seizure disorder
• Known liver failure
• AST/ALT levels >5x normal
• CrCl< 60mL/min
• History of Reynaud's disease
• Planned surgeries in the next 3 months
• Enrolled in another HIV and/or substance use medication intervention study
• Taking naltrexone in the past 30 days
• Taking gabapentin in the past 30 days
• Taking pregabalin in the past 30 days
• Diagnosis of chronic obstructive pulmonary disease (COPD)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

Boston Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey H. Samet, MD, MA, MPH

Role: PRINCIPAL_INVESTIGATOR

Boston University/Boston Medical Center

Locations

First St. Petersburg Pavlov State Medical University

Saint Petersburg, , Russia

Countries

Russia

References

Tsui JI, Rossi SL, Cheng DM, Bendiks S, Vetrova M, Blokhina E, Winter M, Gnatienko N, Backonja M, Bryant K, Krupitsky E, Samet JH. Pilot RCT comparing low-dose naltrexone, gabapentin and placebo to reduce pain among people with HIV with alcohol problems. PLoS One. 2024 Feb 26;19(2):e0297948. doi: 10.1371/journal.pone.0297948. eCollection 2024.

Reference Type: DERIVED

PMID: 38408060 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://www.urbanarch.org

URBAN ARCH, a member of NIAAA CHAART (Consortiums for HIV/AIDS \& Alcohol Research Translation) initiative, conducts and disseminates interdisciplinary research on how alcohol impacts people with HIV and develops interventions to reduce related outcomes.

Other Identifiers

UH3AA026193

Identifier Type: NIH

Identifier Source: secondary_id

View Link

H-39162

Identifier Type: -

Identifier Source: org_study_id