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Ensayos clínicos

Ensayos clínicos

Combination Pain Therapy in HIV Neuropathy

Patrocinador(es) del estudio: National Institute of Allergy and Infectious Diseases (NIAID)
Números de identificación: NCT00863057, ACTG A5252
  • Terminado

Propósito del estudio

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.

Afección:Fase:
Infecciones por el VIH
Peripheral Neuropathy
Fase 2

Detalles del estudio

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.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.

Criterios de inclusión

    :
    • 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

Criterios de exclusión

    :
    • 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

Centros de estudio/contactos

California

    Ucsd, Avrc Crs, San Diego, California, 92103, United States

    Harbor-UCLA Med. Ctr. CRS, Torrance, California, 90502, United States

Colorado

    University of Colorado Hospital CRS, Aurora, Colorado, 80045, United States

Illinois

    Northwestern University CRS, Chicago, Illinois, 60611, United States

Massachusetts

    Massachusetts General Hospital ACTG CRS, Boston, Massachusetts, 02114, United States

Missouri

    Washington U CRS, St. Louis, Missouri, 63110, United States

Ohio

    MetroHealth CRS, Cleveland, Ohio, 44109, United States

Texas

    Houston AIDS Research Team CRS, Houston, Texas, 77030, United States

Actualizado: 15 de abril del 2010

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