HIV InfectionsPhase 2NCT00863057
Combination Pain Therapy in HIV Neuropathy
A Phase 2 study testing Duloxetine and Methadone in people with HIV Infections and Peripheral Neuropathy, run by National Institute of Allergy and Infectious Diseases (NIAID) at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections, Peripheral Neuropathy
- What is being tested?
- Duloxetine and Methadone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 8 sitesUnited States
- Study dates
- May 2009to Dec 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Colorado Hospital CRS
Aurora, Colorado, 80045
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, 02114
Northwestern University CRS
Chicago, Illinois, 60611
MetroHealth CRS
Cleveland, Ohio, 44109
Houston AIDS Research Team CRS
Houston, Texas, 77030
Ucsd, Avrc Crs
San Diego, California, 92103
Washington U CRS
St Louis, Missouri, 63110
Harbor-UCLA Med. Ctr. CRS
Torrance, California, 90502
About this study
Official title: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Duloxetine and Methadone for the Treatment of HIV-Associated Painful Peripheral Neuropathy
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.
Read the detailed 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:
- duloxetine and methadone placebo
- methadone and duloxetine placebo
- duloxetine and methadone
- 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.
- Conditions
- HIV Infections, Peripheral Neuropathy
- Being tested
- Duloxetine, Duloxetine placebo, Methadone, Methadone placebo
- Keywords
- HIV Infections, Neuropathy, Pain
- Medical subject headings
- HIV Infections, Peripheral Nervous System Diseases, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DuloxetineDrug
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.
Duloxetine placeboDrug
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.
MethadoneDrug
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.
Methadone placeboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will receive treatment in the following order: (Period 1, Weeks 1 to 4) duloxetine and methadone placebo, (Period 2, Weeks 6 to 9) duloxetine placebo and methadone, (Period 3, Weeks 11 to 14) duloxetine and methadone, (Period 4, Weeks 16 to 19) duloxetine placebo and methadone placebo Receives: Drug: Duloxetine; Drug: Duloxetine placebo; Drug: Methadone; Drug: Methadone placebo |
| 2 | Experimental | Participants will receive treatment in the following order: (Period 1, Weeks 1 to 4) duloxetine placebo and methadone, (Period 2, Weeks 6 to 9) duloxetine placebo and methadone placebo, (Period 3, Weeks 11 to 14) duloxetine and methadone placebo, (Period 4, Weeks 16 to 19) duloxetine and methadone Receives: Drug: Duloxetine; Drug: Duloxetine placebo; Drug: Methadone; Drug: Methadone placebo |
| 3 | Experimental | Participants will receive treatment in the following order: (Period 1, Weeks 1 to 4) duloxetine and methadone, (Period 2, Weeks 6 to 9) duloxetine and methadone placebo, (Period 3, Weeks 11 to 14) duloxetine placebo and methadone placebo, (Period 4, Weeks 16 to 19) duloxetine placebo and methadone Receives: Drug: Duloxetine; Drug: Duloxetine placebo; Drug: Methadone; Drug: Methadone placebo |
| 4 | Experimental | Participants will receive treatment in the following order: (Period 1, Weeks 1 to 4) duloxetine placebo and methadone placebo, (Period 2, Weeks 6 to 9) duloxetine and methadone, (Period 3, Weeks 11 to 14) duloxetine placebo and methadone, (Period 4, Weeks 16 to 19) duloxetine and methadone placebo Receives: Drug: Duloxetine; Drug: Duloxetine placebo; Drug: Methadone; Drug: Methadone placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weekly Mean Pain Score Derived From Self-reported Average Daily Pain Intensity on an 11-point Likert Scale
Pain was measured on an 11-point Likert numerical rating scale, ranging from 0=''No pain" to 10=''Pain as bad as you can imagine".
Participants were given pain diaries at weeks 0, 5, 10, and 15. They started the diary 7 days prior to their clinic visits at weeks 0, 4, 9, 14, and 19. During the 7 days, each morning, they recorded their pain level due to neuropathy by circling the number that best described their neuropathy pain on average over the past 24 hours.
Measured: During the fourth treatment week of each treatment period
Secondary outcomes (10)
Number of Participants With 30% or More Improvement in Mean Pain Score on an 11-point Likert Scale
Pain was measured on an 11-point Likert numerical rating scale, ranging from 0=''No pain" to 10=''Pain as bad as you can imagine" at baseline and over the fourth treatment week of each treatment period.
The % of improvement was calculated as (x-y)/x,where x was the MPI score at baseline, and y was the MPI score at the end of each treatment stage.
Measured: At Baseline and over the fourth treatment week of each treatment period
Number of Participants With 50% or More Improvement in Mean Pain Score on an 11-point Likert Scale
Pain was measured on an 11-point Likert numerical rating scale, ranging from 0=''No pain" to 10=''Pain as bad as you can imagine" at baseline and over the fourth treatment week of each treatment period.
The % of improvement was calculated as (x-y)/x,where x was the MPI score at baseline, and y was the MPI score at the end of each treatment stage.
Measured: At Baseline and over the fourth treatment week of each treatment period
Mean Nighttime Pain Measure on an 11-point Likert Scale
Pain was measured on an 11-point Likert numerical rating scale, ranging from 0=''No pain" to 10=''Pain as bad as you can imagine".
Participants were given pain diaries at weeks 0, 5, 10, and 15. They started the diary 7 days prior to their clinic visits at weeks 0, 4, 9, 14, and 19. During the 7 days, each morning, they recorded their pain level due to neuropathy by circling the number that best described their neuropathy pain on average during the night time.
Measured: Over the fourth treatment week of each treatment period
Pain-related Interference Measured by the Brief Pain Inventory (BPI) Interference Items
The BPI interference scale measured level of interference with the following seven items:
- General activity
- Mood
- Walking ability
- Normal work
- Relations with other people
- Sleep
- Enjoyment of life
Interference scales range from 0='Does not interfere' to 10='Completely interferes'. The overall BPI score is the mean of seven item with the minimum and maximal scores of 0 and 70, respectively.
Measured: At the fourth week of each treatment period
Quality of Life Measured by SF-36 Healthy Survey (SF-36)
The data for this outcome are not available for the analysis due to an issue with a company which provides software to calculate SF-36.
Measured: At the fourth treatment week of each treatment period
Emotional Functioning as Measured by the Center for Epidemiologic Studies Depression Scale (CES-D)
The CES-D is a 20-item self-report rating inventory measuring characteristic attitudes and symptoms of depression. Participants were asked to score each item: (0) Rarely, (1) Occasionally, (2) Sometimes, and (3) Most of time. Some items are multiplied by -1 to change direction. The overall CES-D score is simply the sum of 20 items. The highest possible total CES-D score is 48, and the lowest possible score is -12. The total CES-D score is considered missing if more than 4 items are not answered.
Measured: At the fourth treatment week of each treatment period
Patient and Clinician Global Impression of Change (PGIC and CGIC) on a 7-point Likert Scale
The GIC scale is a validated instrument that consists of seven verbal descriptors on a 7-point scale:
- Very much improved
- Much improved
- Minimally improved
- No change
- Minimally worse
- Much worse
- Very much worse
Participants were carefully instructed to consider the impact of study treatments on their level of neuropathic pain intensity during the baseline phase of the study.
Measured: At the fourth treatment week of each treatment period
Use of Rescue Medication (Acetaminophen)
Measured: During each treatment period and the subsequent cross-over (or final study week) period
Maximum Tolerated Dose of Duloxetine and Methadone
Measured: During each treatment period
Number of Participants With Treatment-emergent Grade 2 to 4 Adverse Events
The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 was used (see the link to the grading table in Protocol Section)
Measured: From study entry to end of study at week 20 or premature study discontinuation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2009 (estimated)
- Study startMay 2009
- Primary completionDec 2010
- Study completionDec 2010
Why it stopped: Due to slow rate of enrollment, which compromised the ability to meet study objectives in a timely manner.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- David B. Clifford, MD, Study chair, Washington University School of MedicineTaylor B. Harrison, MD, Study chair, Emory University, Department of Neurology, Neuromuscular Division
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00863057
- Sponsor's protocol ID
- A5252
- Other IDs
- 10636, ACTG A5252
- Status last verified
- Feb 2019
- First submitted
- 16 Mar 2009
- Last updated
- 4 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Evans SR, Clifford DB, Kitch DW, Goodkin K, Schifitto G, McArthur JC, Simpson DM. Simplification of the research diagnosis of HIV-associated sensory neuropathy. HIV Clin Trials. 2008 Nov-Dec;9(6):434-9. doi: 10.1310/hct0906-434.
PubMed 19203909Valcour V, Yeh TM, Bartt R, Clifford D, Gerschenson M, Evans SR, Cohen BA, Ebenezer GJ, Hauer P, Millar L, Gould M, Tran P, Shikuma C, Souza S, McArthur JC; AIDS Clinical Trials Group (ACTG) 5157 protocol team. Acetyl-l-carnitine and nucleoside reverse transcriptase inhibitor-associated neuropathy in HIV infection. HIV Med. 2009 Feb;10(2):103-10. doi: 10.1111/j.1468-1293.2008.00658.x.
PubMed 19200173Harrison T, Miyahara S, Lee A, Evans S, Bastow B, Simpson D, Gilron I, Dworkin R, Daar ES, Wieclaw L, Clifford DB; ACTG A5252 Team. Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies. Pain Med. 2013 Jul;14(7):1039-47. doi: 10.1111/pme.12084. Epub 2013 Apr 8.
PubMed 23565581
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Duloxetine and Methadone for the Treatment of HIV-Associated Painful Peripheral Neuropathy
- ClinicalTrials.gov ID
- NCT00863057
- Acronym / sponsor ID
- A5252
- Conditions
- HIV Infections, Peripheral Neuropathy
- Keywords
- HIV Infections, Neuropathy, Pain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to slow rate of enrollment, which compromised the ability to meet study objectives in a timely manner.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- May 2009 (actual)
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 17 Mar 2009 (estimated)
- Results
- Posted 25 Apr 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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:
- duloxetine and methadone placebo
- methadone and duloxetine placebo
- duloxetine and methadone
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Duloxetine, Drug: Duloxetine placebo, Drug: Methadone, Drug: Methadone placeboParticipants will receive treatment in the following order: (Period 1, Weeks 1 to 4) duloxetine and methadone placebo, (Period 2, Weeks 6 to 9) duloxetine placebo and methadone, (Period 3, Weeks 11 to 14) duloxetine and methadone, (Period 4, Weeks 16 to 19) duloxetine placebo and methadone placebo |
| 2 | Experimental | Drug: Duloxetine, Drug: Duloxetine placebo, Drug: Methadone, Drug: Methadone placeboParticipants will receive treatment in the following order: (Period 1, Weeks 1 to 4) duloxetine placebo and methadone, (Period 2, Weeks 6 to 9) duloxetine placebo and methadone placebo, (Period 3, Weeks 11 to 14) duloxetine and methadone placebo, (Period 4, Weeks 16 to 19) duloxetine and methadone |
| 3 | Experimental | Drug: Duloxetine, Drug: Duloxetine placebo, Drug: Methadone, Drug: Methadone placeboParticipants will receive treatment in the following order: (Period 1, Weeks 1 to 4) duloxetine and methadone, (Period 2, Weeks 6 to 9) duloxetine and methadone placebo, (Period 3, Weeks 11 to 14) duloxetine placebo and methadone placebo, (Period 4, Weeks 16 to 19) duloxetine placebo and methadone |
| 4 | Experimental | Drug: Duloxetine, Drug: Duloxetine placebo, Drug: Methadone, Drug: Methadone placeboParticipants will receive treatment in the following order: (Period 1, Weeks 1 to 4) duloxetine placebo and methadone placebo, (Period 2, Weeks 6 to 9) duloxetine and methadone, (Period 3, Weeks 11 to 14) duloxetine placebo and methadone, (Period 4, Weeks 16 to 19) duloxetine and methadone placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DuloxetineDuring 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. | Drug | 1, 2, 3, 4 |
| Duloxetine placeboDuring 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. | Drug | 1, 2, 3, 4 |
| MethadoneDuring 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. | Drug | 1, 2, 3, 4 |
| Methadone placeboDuring 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. | Drug | 1, 2, 3, 4 |
Primary outcome
Weekly Mean Pain Score Derived From Self-reported Average Daily Pain Intensity on an 11-point Likert Scale
Time frame: During the fourth treatment week of each treatment period
Pain was measured on an 11-point Likert numerical rating scale, ranging from 0=''No pain" to 10=''Pain as bad as you can imagine". Participants were given pain diaries at weeks 0, 5, 10, and 15. They started the diary 7 days prior to their clinic visits at weeks 0, 4, 9, 14, and 19. During the 7 days, each morning, they recorded their pain level due to neuropathy by circling the number that best described their neuropathy pain on average over the past 24 hours.
10 secondary outcomes
Number of Participants With 30% or More Improvement in Mean Pain Score on an 11-point Likert Scale
Time frame: At Baseline and over the fourth treatment week of each treatment period
Number of Participants With 50% or More Improvement in Mean Pain Score on an 11-point Likert Scale
Time frame: At Baseline and over the fourth treatment week of each treatment period
Mean Nighttime Pain Measure on an 11-point Likert Scale
Time frame: Over the fourth treatment week of each treatment period
Pain-related Interference Measured by the Brief Pain Inventory (BPI) Interference Items
Time frame: At the fourth week of each treatment period
Quality of Life Measured by SF-36 Healthy Survey (SF-36)
Time frame: At the fourth treatment week of each treatment period
Emotional Functioning as Measured by the Center for Epidemiologic Studies Depression Scale (CES-D)
Time frame: At the fourth treatment week of each treatment period
Patient and Clinician Global Impression of Change (PGIC and CGIC) on a 7-point Likert Scale
Time frame: At the fourth treatment week of each treatment period
Use of Rescue Medication (Acetaminophen)
Time frame: During each treatment period and the subsequent cross-over (or final study week) period
Maximum Tolerated Dose of Duloxetine and Methadone
Time frame: During each treatment period
Number of Participants With Treatment-emergent Grade 2 to 4 Adverse Events
Time frame: From study entry to end of study at week 20 or premature study discontinuation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19203909Evans SR, Clifford DB, Kitch DW, Goodkin K, Schifitto G, McArthur JC, Simpson DM. Simplification of the research diagnosis of HIV-associated sensory neuropathy. HIV Clin Trials. 2008 Nov-Dec;9(6):434-9. doi: 10.1310/hct0906-434.
- Background: PubMed 19200173Valcour V, Yeh TM, Bartt R, Clifford D, Gerschenson M, Evans SR, Cohen BA, Ebenezer GJ, Hauer P, Millar L, Gould M, Tran P, Shikuma C, Souza S, McArthur JC; AIDS Clinical Trials Group (ACTG) 5157 protocol team. Acetyl-l-carnitine and nucleoside reverse transcriptase inhibitor-associated neuropathy in HIV infection. HIV Med. 2009 Feb;10(2):103-10. doi: 10.1111/j.1468-1293.2008.00658.x.
- Derived from this study: PubMed 23565581Harrison T, Miyahara S, Lee A, Evans S, Bastow B, Simpson D, Gilron I, Dworkin R, Daar ES, Wieclaw L, Clifford DB; ACTG A5252 Team. Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies. Pain Med. 2013 Jul;14(7):1039-47. doi: 10.1111/pme.12084. Epub 2013 Apr 8.
- The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David B. Clifford, MD study chair
Washington University School of Medicine
Taylor B. Harrison, MD study chair
Emory University, Department of Neurology, Neuromuscular Division
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Duloxetine and Methadone in people with HIV Infections and Peripheral Neuropathy, run by National Institute of Allergy and Infectious Diseases (NIAID) at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Apr 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Weekly Mean Pain Score Derived From Self-reported Average Daily Pain Intensity on an 11-point Likert Scale (time frame: During the fourth treatment week of each treatment period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00863057, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.