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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Polyneuropathy; HIV-associated Neuropathy
• Intervention / Treatment: Drug: methadone; Drug: SAB placebo; Drug: SAB378; Drug: Methadone placebo

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92093
      • University of California, San Diego
  • New York
    • Brooklyn, New York, United States, 11208
      • University of New York Downstate Medical Center
    • Rochester, New York, United States, 14620
      • University of Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 1; methadone plus SAB placebo	Drug: methadone; 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.; Drug: SAB placebo; an inactive substance
EXPERIMENTAL: 2; methadone plus active SAB	Drug: methadone; 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.; Drug: SAB378; 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; Other Names: SAB
PLACEBO_COMPARATOR: 3; methadone placebo plus SAB placebo	Drug: SAB placebo; an inactive substance; Drug: Methadone placebo; Methadone placebo

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (ACTUAL): January 1, 2010
• Study Completion (ACTUAL): January 1, 2010

Study Registration Dates

• First Submitted: July 28, 2008
• First Submitted That Met QC Criteria: July 28, 2008
• First Posted (ESTIMATE): July 29, 2008

Study Record Updates

• Last Update Posted (ACTUAL): February 9, 2018
• Last Update Submitted That Met QC Criteria: February 8, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: HIV; AIDS; Cannabis; methadone; cannabinoid; polyneuropathy; HIV-associated neuropathy; distal sensory polyneuropathy
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Polyneuropathies; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Methadone
• Other Study ID Numbers: U01NS32228_NARC011; NARC 011