HIV Infections Clinical Research Study

What is the purpose of this study?

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.

Can I participate in this study?

You may be eligible for this study if you meet the following criteria:

• Conditions: HIV Infections, Peripheral Neuropathy
• Age: Between 18 - 100 Years
• Gender: Male or Female
• +

  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

  tudy 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

Detail Study Description

Peripheral neuropathy is now recognized as the most common neurological complication of HIV disease and its treatment. Before highly active antiretroviral therapy (HAART) was introduced, the prevalence of HIV-associated distal sensory polyneuropathy (DSP) was already estimated to be 35%, mostly contained to populations with moderate to advanced immunosuppression. Now, since the advent of HAART, the prevalence of HIV-associated neuropathy has increased to 52%, possibly due to a combination of antiretroviral toxic neuropathy (ATN), decreased mortality, and accumulated medical comorbidities. Successful treatment of neuropathic pain is inherently difficult, and treatment of HIV-associated neuropathic pain is particularly complicated. To date, evidence supporting effective therapies for neuropathic HIV-associated pain is lacking, despite several types and classes of drugs having been evaluated in clinical trials. This study will evaluate the safety and efficacy of duloxetine, methadone, and the combination of duloxetine and methadone in painful HIV-associated neuropathy. Both of these drugs are approved by the Food and Drug Administration (FDA) but for purposes unrelated to HIV-associated neuropathy, and no previous studies have utilized these two treatments for this purpose. For this study, 120 participants with painful HIV-associated neuropathy will be recruited. The trial will last for approximately 23 weeks. Each participant will receive a total of 4 study treatments. The following treatment pairings will be given in a sequence determined by randomization: 1. duloxetine and methadone placebo 2. methadone and duloxetine placebo 3. duloxetine and methadone 4. duloxetine placebo and methadone placebo Each treatment period will last 4 weeks and will be followed by a 1-week combined taper and washout. People wishing to enroll in this study will have a screening visit that will last about 3 hours. During this visit, participants will have an HIV test, physical exam, neurologic exam, blood drawn, electrocardiogram (EKG), and a pregnancy test, if applicable. Participants will also be asked about their current health and any medications they may be taking. They will also be asked about their mood and be given the results of tests performed at the screening visit. If screening qualifies participants for the study, they will return for a pre-entry visit lasting 2 hours. During this visit, participants will have a limited physical exam and be asked about changes in their health or medicines since screening. Participants will also be given a pain diary with instructions to record neuropathy pain every day for each of the 7 days before beginning the study and throughout the study. After beginning the study, participants will return to the clinic for another 8 visits. These visits are at the end of each 4-week treatment period and at the end of each 1-week crossover period. At each visit, there will be a limited physical exam and participants will answer questions about their health and medications. Participants will also be told the results of routine lab tests and pregnancy tests performed during the study.

Study Treatments

Duloxetine, Duloxetine placebo, Methadone, Methadone placebo

Last Updated: May 2010