St. PETERsburg Pain and Alcohol Intervention With Naltrexone and Gabapentin

Phase 2

Completed

Conditions: Alcohol Use, Unspecified
Chronic Pain
HIV Infections

Interventions: Drug: Low-dose naltrexone
Drug: Placebo
Drug: Gabapentin

Registration Number: NCT04052139

Lead Sponsor: Boston Medical Center

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 45

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low-dose naltrexone	Low-dose naltrexone	Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.
Placebo	Placebo	Participants will receive a placebo to be taken three times daily for 8 weeks.
Gabapentin	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).

Primary Outcome Measures

Name	Time	Method
Change in Past Week Pain Interference	Baseline, 8-weeks	Change in past week pain interference (score 0 \[no pain\]-10 \[high pain\]) from baseline to week 8. Pain interference will be measured using the Brief Pain Inventory, which allows patients to rate the severity of their pain and the degree to which their pain interferes with common dimensions of feeling and function
Change in Past Week Pain Severity	Baseline, 8-weeks	Change in past week pain severity (score 0 \[no pain\] -10 \[high pain\]) from baseline to week 8. Pain severity will be measured using the Brief Pain Inventory, which allows patients to rate the severity of their pain and the degree to which their pain interferes with common dimensions of feeling and function

Secondary Outcome Measures

Name	Time	Method
Change in Cold Pain Tolerance	Baseline, 8-weeks	Mean change in the number of seconds a participant can keep their hand submerged in a container of iced water. Participants were instructed to keep their hand in as long as they could, up to 3 minutes.
Change in TNF-alpha	Baseline, 8-weeks	Mean change in TNF-alpha values measured on blood samples collected using commercially available enzyme-linked immunosorbent assay kits (R\&D Systems).
Change in IL-1beta	Baseline, 8-weeks	Mean change in IL-1beta values measured on blood samples collected using commercially available enzyme-linked immunosorbent assay kits (R\&D Systems).
Change in Biomarker IL-10	Baseline, 8 weeks	Mean change in IL-10 values measured on blood samples collected using commercially available enzyme-linked immunosorbent assay kits (R\&D Systems).
Change in CD4 Count	Baseline, 8-weeks	Defined as mean change in CD4 values from lab assay
Change in Percentage of Past Month Heavy Drinking Days	Baseline, 8-weeks	Mean percentage of change in self-reported heavy drinking in the past 30 days of alcohol consumption obtained via the Timeline Followback (TLFB) method. The NIAAA definition of heavy drinking is used (\> 4 drinks in a day for men; \> 3 drinks in a day for women). Participants were asked about their alcohol consumption on each day in the previous 30 days.
Number of Participants With a Change in HIV Viral Load Suppression Status	Baseline, 8-weeks	Defined as number of participants who change from suppressed to unsuppressed or unsuppressed to suppressed from lab tests
Change in Biomarker IL-6	Baseline, 8-weeks	Mean change in IL-6 values measured on blood samples collected using commercially available enzyme-linked immunosorbent assay kits (R\&D Systems).