Combination Pain Therapy in HIV Neuropathy
Condition: HIV Infections; Peripheral Neuropathy
MeSH terms: HIV Infections; Peripheral Nervous System Diseases
Intervention: Duloxetine; Duloxetine placebo; Methadone; Methadone placebo
Intervention description: During each treatment period, participants will take duloxetine in the following doses. On Days 1 to 5, participants will take one 30-mg capsule orally, once daily. On Days 6 to 28, participants will take two 30-mg capsules orally, once daily. During days 29 to 31 dosage will be reduced to one capsule daily and then discontinued on Day 32.; During each treatment period, participants will take duloxetine placebo in the following doses. On Days 1 to 5, participants will take one 30-mg capsule orally, once daily. On Days 6 to 28, participants will take two 30-mg capsules orally, once daily. During days 29 to 31 dosage will be reduced to one capsule daily and then discontinued on Day 32.; During each treatment period, participants will take methadone in the following doses. On Days 1 to 5, participants will take one 5-mg capsule orally, twice daily. On Days 6 to 10, participants will take one 5-mg capsule orally, three times daily. On Days 11 to 28, participants will take two 5-mg capsules orally, three times daily. On Days 29 to 31, dosage will be one 5-mg capsule orally, three times daily. On Days 32 to 34, dosage will be decreased to one 5-mg capsule, twice daily and ultimately discontinued on Day 35.; During each treatment period, participants will take methadone placebo in the following doses. On Days 1 to 5, participants will take one 5-mg capsule orally, twice daily. On Days 6 to 10, participants will take one 5-mg capsule orally, three times daily. On Days 11 to 28, participants will take two 5-mg capsules orally, three times daily. On Days 29 to 31, dosage will be one 5-mg capsule orally, three times daily. On Days 32 to 34, dosage will be decreased to one 5-mg capsule, twice daily and ultimately discontinued on Day 35.
Intervention MeSH terms: Duloxetine Hydrochloride; Methadone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV Infections; Neuropathy; Pain

Summary:

      Neuropathy results from damage to the nerves in the feet and legs. It is usually experienced
      as pain, tingling or numbness. In HIV-infected people, neuropathy can result from the
      infection itself or be a side effect of antiretroviral treatment. The purpose of this study
      is to determine whether two different drugs, methadone and duloxetine, reduce
      neuropathy-associated pain in HIV-infected people. This study will also examine whether
      utilization of both of these drugs is more effective than treatment with only one.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV infected

          -  HIV-associated neuropathy

          -  Able and willing to provide informed consent

          -  Successful completion of a daily baseline pain diary over 1 week immediately prior to
             entry with a mean pain intensity of 4 or more on an 11-point Likert scale

          -  Karnofsky performance score of 60 or more within 45 days prior to entry

          -  Required laboratory values. More information on this criterion can be found in the
             study protocol.

          -  Willing to comply with protocol requirements for the duration of the study, to include
             daily completion of the pain diary as instructed, attendance at all study visits, and
             avoidance of prohibited medications

          -  On stable or no antiretroviral therapy for 30 days prior to entry. Participants on ARV
             therapy should plan to remain on the same regimen and drug dose for the duration of
             the study. Participants not on ARV therapy should have no plans to initiate therapy
             during study enrollment.

          -  Not pregnant

        Exclusion Criteria:

          -  Conditions that confound a diagnosis of HIV-associated neuropathy or preclude accurate
             assessment of neuropathy symptoms, at the discretion of the site investigator. More
             information on this criterion can be found in the study protocol.

          -  Potential for unstable neuropathy symptoms during study participation due tthe
             following: (1) discontinuation of dideoxynucleoside nucleoside reverse transcriptase
             inhibitor (NRTI) within 16 weeks prior to entry, (2)treatment within 120 days prior to
             entry with any drug that the site investigator considers may contribute to sensory
             neuropathy

          -  Current history of significant depression on antidepressant therapy precluding
             withdrawal from antidepressants, upon impression of site investigator with input from
             the participant's mental health provider where available

          -  History of active substance abuse or dependence identified through medical chart
             review or self-report such that, in the opinion of the site investigator,
             participation poses undue risk for the participant

          -  History of alcohol-related complications within 6 months prior to entry that include
             but are not restricted to alcohol withdrawal seizures, alcoholic hallucinosis,
             delirium tremens, or being in an alcohol detoxification program - Treatment with
             tricyclic antidepressants, selective serotonin reuptake inhibitors, selective
             norepinephrine reuptake inhibitors (SNRIs), bupropion, or tramadol that, upon judgment
             of the site investigator, cannot be tapered and discontinued prior to the pre-entry
             visit

          -  Treatment with an analgesic opioid regimen of more than 60 mg oral morphine equivalent
             per day within 45 days prior to entry

          -  Cognitive impairment that, in the opinion of the site investigator and based on
             clinical impression, might impact the ability to comply with the study protocol

          -  Use of an investigational agent within 45 days prior to entry except for
             expanded-access drugs or drugs used in an ACTG protocol for HIV treatment or for
             HIV-associated complications, if the drug is not prohibited by this protocol

          -  Acute active AIDS-defining opportunistic infection (OI) within 30 days prior to entry.
             Participants with no evidence of active disease and receiving maintenance therapy of
             AIDS-related OIs will be eligible

          -  Serious illness requiring systemic treatment and/or hospitalization within 45 days
             prior to entry

          -  End-stage renal dialysis requiring hemodialysis

          -  History of known or suspected hepatic cirrhosis diagnosed by signs and symptoms,
             radiography, or prior liver biopsy with Metavir score of more than 2

          -  Prolonged QTc interval (more than 0.45 seconds) within 90 days prior to entry

          -  Felt to be at high risk of opioid-induced respiratory compromise. More information on
             this criterion can be found in the study protocol.

          -  Diagnosis of a new seizure disorder or seizure within 90 days prior to entry

          -  History of acute angle-closure glaucoma, at the discretion of the site investigator

          -  Known allergy/sensitivity or any hypersensitivity to duloxetine, methadone,
             acetaminophen, or their ingredients

          -  Breastfeeding