Combination of an Investigational Cannabinoid and Methadone for HIV-associated Neuropathy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness of methadone alone and in combination with SAB378 for the treatment of painful HIV-associated neuropathy.

Detailed Description
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Distal sensory polyneuropathy is the most common neurological complication of HIV disease and its treatment. To date no standard effective therapy has been identified. In this study, scientists will evaluate the effectiveness of treating HIV-associated neuropathy with methadone alone and in combination with a novel cannabinoid SAB378. A cannabinoid is a molecule found only in the Cannabis plant. Cannabis and some cannabinoids are effective analgesics or pain relievers. The rationale for combination therapy is twofold: (1) medications with unique mechanisms of action may affect different aspects of neuropathic pain and (2) combination therapy may act synergistically-meaning the combined effect may be greater than the effect of each drug alone. Approximately 84 participants will be enrolled in this double-blind, placebo-controlled, crossover study. Participants will be randomly assigned to three treatment groups-those receiving methadone and SAB378 placebo (an inactive substance), those receiving methadone and active SAB378, or those receiving methadone placebo and SAB378 placebo. All participants will be exposed to each of the 3 treatment groups during the study. This trial is part of the Neurologic AIDS Research Consortium, an effective collaborative clinical study group dedicated to the study of HIV-associated neurological disease.

Official Title
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NARC 011: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Methadone and Combination of Methadone and SAB378 in HIV-associated Painful Peripheral Neuropathy

Conditions
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HIV-associated Neuropathy, Polyneuropathy

Intervention / Treatment
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* Drug: SAB378
* Drug: methadone
* Drug: SAB placebo
* Drug: Methadone placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infection HIV-associated neuropathy diagnosed by a neurologist Presence of at least a moderate pain score on the basis of completion of a baseline pain diary Stable antiretroviral regimen for at least 8 weeks prior to study entry. Hemoglobin ≥ 8.0 g/dL for males and ≥ 7.5 g/dL for females Exclusion Criteria: Active AIDS-defining opportunistic infection within 45 days prior to study entry Renal insufficiency Chronic liver disease B12 deficiency Family history of hereditary neuropathy Discontinuation of dideoxynucleoside NRTI within 16 weeks prior to entry On neuroregenerative therapy Treatment with neurotoxic drugs within 120 days prior to entry Respiratory compromise Hypotension Active substance abuse or dependence History of alcohol-related complications within 6 months prior to screening Women of childbearing potential

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>methadone plus SAB placebo | Drug: methadone<br>* Methadone 5 mg BID (twice a day) for 5 days, then 5 mg TID (three times a day) for 5 days, to maximum of 10 mg TID, in combination with SAB placebo or SAB active drug titrated as above, to end of 28-day treatment period.<br>Drug: SAB placebo<br>* an inactive substance<br>|
| Experimental: 2<br>methadone plus active SAB | Drug: SAB378<br>* SAB 15 mg per day for 5 days, the 15 mg BID (twice a day) for 5 days, then 15 mg TID (three times a day) to end of 28-day treatment period, in combination with active methadone 5 mg BID for 5 days, then 5 mg TID for 5 days, to maximum of 10 mg TID until end of 28-day treatment period<br>* Other names: SAB;Drug: methadone<br>* Methadone 5 mg BID (twice a day) for 5 days, then 5 mg TID (three times a day) for 5 days, to maximum of 10 mg TID, in combination with SAB placebo or SAB active drug titrated as above, to end of 28-day treatment period.<br>|
| Placebo Comparator: 3<br>methadone placebo plus SAB placebo | Drug: SAB placebo<br>* an inactive substance<br>Drug: Methadone placebo<br>* Methadone placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of methadone alone versus methadone and SAB378 for treatment of HIV-associated neuropathy |  | At the end of each 4-week treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on quality of life, emotional functioning, cognitive functioning, safety |  | At the end of each 4-week treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-associated neuropathy, HIV, AIDS, cannabinoid, Cannabis, methadone, distal sensory polyneuropathy, polyneuropathy