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

ID: NCT00723918
Status: Withdrawn
Phase: Phase 2
Start Date: April 01, 2009
First Submitted: July 28, 2008
Last Updated: February 08, 2018
Results: N/A
Sponsors & Collaborators: Washington University School of Medicine, National Institute of Neurological Disorders and Stroke (NINDS)
Location: United States
Conditions: HIV-associated Neuropathy, Polyneuropathy
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Study Description

Brief Summary

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

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.
Condition or disease Intervention/treatment Phase

HIV-associated Neuropathy

Polyneuropathy

Drug: SAB378
Other Names
SAB
Drug: methadone
Other Names
Drug: SAB placebo
Other Names
Drug: Methadone placebo
Other Names
Phase 2

Tracking Information

First Submitted DateJuly 28, 2008
Last Update Posted DateFebruary 08, 2018
Start DateApril 01, 2009
Actual Completion DateJanuary 01, 2010
Primary Completion DateJanuary 01, 2010
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Efficacy of methadone alone versus methadone and SAB378 for treatment of HIV-associated neuropathy [Time Frame: At the end of each 4-week treatment period]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Effect on quality of life, emotional functioning, cognitive functioning, safety [Time Frame: At the end of each 4-week treatment period]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleCombination of an Investigational Cannabinoid and Methadone for HIV-associated Neuropathy
Official TitleNARC 011: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Methadone and Combination of Methadone and SAB378 in HIV-associated Painful Peripheral Neuropathy
Brief Summary

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

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 TypeInterventional
Study PhasePhase 2
Estimated Enrollment
0
Allocation
Randomized
Interventional Model
Crossover Assignment
Masking
Quadruple
Primary Purpose
Treatment
Conditions
HIV-associated Neuropathy
Polyneuropathy
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
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
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.

Other Names
Drug: SAB placebo

an inactive substance

Other Names
Drug: Methadone placebo

Methadone placebo

Other Names
Study Groups/Cohorts
1
methadone plus SAB placebo

2
methadone plus active SAB

3
methadone placebo plus SAB placebo

Study Arms
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.

Active Comparator 1
methadone plus SAB placebo
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.

Experimental 2
methadone plus active SAB
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

Placebo Comparator 3
methadone placebo plus SAB placebo
Drug : SAB placebo
an inactive substance

Placebo Comparator 3
methadone placebo plus SAB placebo
Drug : Methadone placebo
Methadone placebo

Arm Intervention/Treatment
Active Comparator 1
methadone plus SAB placebo
Drug : methadone
Active Comparator 1
methadone plus SAB placebo
Drug : SAB placebo
Experimental 2
methadone plus active SAB
Drug : methadone
Experimental 2
methadone plus active SAB
Drug : SAB378
Placebo Comparator 3
methadone placebo plus SAB placebo
Drug : SAB placebo
Placebo Comparator 3
methadone placebo plus SAB placebo
Drug : Methadone placebo

Recruitment Information

Recruitment Status:Withdrawn
Enrollment0
Completion DateJanuary 01, 2010
Eligibility Criteria: 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
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Not Available
Listed Location Countries
United States

Administrative Information

NCT Number:NCT00723918
Other Study ID Numbers
U01NS32228_NARC011
NARC 011
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Washington University School of Medicine
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Principal Investigator
David B. Clifford, MD
Professor of Neurology, Washington University