Pregabalin Versus Placebo In The Treatment Of Neuropathic Pain Associated With HIV Neuropathy
- Registration Number
- NCT01049217
- Lead Sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
- Brief Summary
The purpose of this study is to evaluate the efficacy of pregabalin compared to placebo in reducing neuropathic pain associated with HIV neuropathy.
- Detailed Description
Based on DMC interim efficacy analysis results indicating a low probability for success the study was terminated on April 2, 2012; the termination was unrelated to any safety findings that could impact patient health.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 377
- Men and women, ages of 18 or greater
- Documented evidence of HIV-1 infection
- Documented diagnosis of HIV-associated Distal Symmetrical Polyneuropathy (DSP) with subjective sensory symptom of pain
- Pain starts in the feet
- Subject has untreated vitamin B12 deficiency (serum B12 level <200 pg/ml) or if treated B12 deficiency -treatment is less than 6 months of B12 supplementation (injection or intranasal B12) prior to screening
- Diabetes mellitus requiring regular medical treatment (other than diet and exercise) or HbA1C >6.9
- Subjects with peripheral neuropathic pain that is not associated with HIV infection; including subjects with conditions such as: Post Herpetic Neuralgia (PHN), Diabetic Peripheral Neuropathy (DPN), familial neuropathies; compression related neuropathy, radicular pain, other infection related neuropathies (eg, leprosy); neuropathy related to: metabolic abnormalities; nutritional factors; vascular insults; inflammation; autoimmune disease; and malignancy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control placebo - Active drug pregabalin -
- Primary Outcome Measures
Name Time Method Change From Baseline in Mean Pain Score at Endpoint (up to Week 16) Baseline, Endpoint (up to Week 16) Mean pain score was defined as the mean of the last 7 daily diary pain ratings. Participants rated their Human Immunodeficiency Virus (HIV) neuropathy pain over the past 24 hours on an 11-point numeric rating scale ranging from 0 = no pain to 10 = worst possible pain. A rating of 1-3 was considered as mild pain; 4-6 = moderate pain; and 7-10 = severe pain. Endpoint was the last observation for a participant assessed using specified imputation method, modified Baseline Observation Carried Forward (mBOCF).
- Secondary Outcome Measures
Name Time Method Number of Participants Who Were Employed or Unemployed Assessed by Work Productivity and Activity Impairment: Specific Health Problem (WPAI: SHP) Questionnaire Baseline, Week 16, 17 WPAI: 6-question participant rated questionnaire to determine the degree to which specific health problem (SHP) affected work productivity while at work and affected activities outside of work. It assesses amount of absenteeism, presenteeism and daily activity impairment attributable to a HIV neuropathy pain. Number of participants who responded "Yes/No" to Question 1: Are you currently employed (working for pay)? are reported.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) Subscales and Total Intensity Score at Endpoint (up to Week 16) Baseline, Endpoint (up to Week 16) NPSI: participant rated questionnaire to evaluate different symptoms of neuropathic pain (subscales: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. The relevant subscales and total score were transformed to 0-1, higher score indicates a greater intensity of pain. Endpoint=last observation for participant as per imputation method.
Total Sleep Time (TST) and Minutes of Interrupted Sleep (MIS) Baseline (Day -14 to 1), Week 1 through Week 4, Week 12 through Week 16, Endpoint (up to Week 16) Total sleep time is the number of minutes asleep between time of sleep onset to morning awakening and MIS is the number of minutes spent awake after sleep onset to final awakening. TST and MIS were determined by actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to record movements while the device was being worn. Endpoint was the last observation for a participant assessed using specified imputation method.
Number of Participants With Categorical Scores on Patient Global Impression of Change (PGIC) Week 16 PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). Number of participants in each category is reported.
Change From Baseline in Numeric Rating Scale (NRS)-Sleep Interference Score at Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and Endpoint (up to Week 16) Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, Endpoint (up to Week 16) Weekly mean sleep interference score was defined as the mean of the daily sleep interference diary ratings split into 7 day intervals. Participants rated how HIV neuropathy pain has interfered with their sleep during the past 24 hours on an 11-point NRS ranging from 0 = does not interfere with sleep to 10 = completely interferes (unable to sleep due to pain). Endpoint was the last observation for a participant assessed using specified imputation method.
Neuropathic Pain Symptom Inventory (NPSI): Change From Baseline in Number of Participants With Duration of Spontaneous Pain and Number of Pain Attacks at Endpoint (up to Week 16) Baseline, Endpoint (up to Week 16) NPSI: participant-rated questionnaire to evaluate different symptoms of neuropathic pain. It includes 10 descriptors, and 2 temporal items. Results reported for categorical change in temporal items assessed on 5-point scale for duration of spontaneous pain (1=continuously, 2=8-12 hours \[hrs\], 3=4-7 hrs, 4=1-3 hrs, 5=less than 1 hr), numbers of pain attacks (1=more than 20, 2=11-20 attacks, 3=6-10 attacks, 4=1-5 attacks, 5=no attack). Change data categorized as worsened (negative change), unchanged (no change), and improved (positive change). Endpoint=last observation as per imputation method.
Total Activity Counts Baseline (Day -14 to 1), Week 1 through Week 4, Week 12 through Week 16, Endpoint (up to Week 16) Activity counts are the units of motion. It is equal to the sum of peak accelerations each second during the epoch (60 seconds). Total activity counts per day is the sum of the activity counts for each epoch (60 seconds) during the "day" (non sleep period). A total activity count was determined by actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to record movements while the device was being worn. Endpoint was the last observation for a participant assessed using specified imputation method.
Change From Baseline in Medical Outcomes Study-Sleep Scale (MOS-SS) at Endpoint (up to Week 16) Baseline, Endpoint (up to Week 16) Participant-rated 12-item questionnaire to assess constructs of sleep over past week; 7 subscales: sleep disturbance (range 0-100), snoring (range 0-100), awaken short of breath (SOB) or with headache (range 0-100), sleep adequacy (range 0-100), somnolence (range: 0-100); sleep quantity (range: 0-24), optimal sleep (yes/no), and 9 item index measures of sleep disturbance provide composite scores: sleep problems index (range 0-100). Except adequacy, optimal sleep and quantity, higher scores=more impairment. Endpoint was the last observation for a participant assessed using imputation method.
Change From Baseline in Numeric Rating Scale (NRS)-Current Pain Score at Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and Endpoint (up to Week 16) Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, Endpoint (up to Week 16) Weekly current pain score was defined as the mean of the daily current pain diary ratings split into 7 day intervals. Participants rated current ("right now") HIV neuropathy pain an 11-point NRS ranging from 0 = no pain to 10 = worst possible pain. A rating of 1-3 was considered as mild pain; 4-6 = moderate pain; and 7-10 = severe pain. Endpoint was the last observation for a participant assessed using specified imputation method.
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score at Week 4, 8, 12, 16 and Endpoint (up to Week 16) Baseline, Week 4, 8, 12, 16, Endpoint (up to Week 16) BPI-sf:5-item self-administered questionnaire to assess severity,impact of pain on daily functions. Pain Severity Index (PSI):average of Question 1-4 each measured severity of pain over past 24-hours on 11-point scale (0=no pain to 10=worst possible pain). Pain Interference Index (PII):average of 7 pain interference items of Question 5 that measured level of interference of pain on daily function on 11-point scale (0=does not interfere to 10=completely interferes). For PSI, PII range:0-10 higher score=higher pain/interference. Endpoint=last observation for participant as per imputation method.
Sleep Efficiency Baseline (Day -14 to 1), Week 1 through Week 4, Week 12 through Week 16, Endpoint (up to Week 16) Sleep efficiency is the time spent asleep divided by total time between sleep onset and sleep end, multiplied by 100. Sleep efficiency was determined by actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to record movements while the device was being worn. Endpoint was the last observation for a participant assessed using specified imputation method.
Percentage Day Time Above Sedentary Level Baseline (Day -14 to 1), Week 1 through Week 4, Week 12 through Week 16, Endpoint (up to Week 16) Percentage of time above sedentary level is number of epochs (60 seconds) with greater than (\>) 200 activity counts per minute divided by total number of epochs during the "day" (non sleep period) multiplied by 100. This was determined by actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to record movements while the device was being worn. Endpoint was the last observation for a participant assessed using specified imputation method.
Change From Baseline in Hospital Anxiety and Depression Scales (HADS) at Endpoint (up to Week 16) Baseline, Endpoint (up to Week 16) HADS: participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. Endpoint was the last observation for a participant assessed using imputation method.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) at Endpoint (up to Week 16) Baseline, Endpoint (up to Week 16) SF-36 is a standardized survey evaluating 8 domains of functional health and well being: physical and social (So) functioning (Fn), physical and emotional role (role-physical \[R-P\], role-emotional \[R-E\]) limitations, bodily pain (BP), general health (GH), vitality (Vit), mental health (MnH). Two summary scores include Physical Component (Ph C) and Mental Component (Mn C). The score for a section is an average of the individual question scores. Score range for domain scores and summary scores: 0-100 (100=highest level of functioning).
Number of Participants With Categorical Scores on Clinician Global Impression of Change (CGIC) Week 16 The CGIC scale measures a physician's global impression of a participant's clinical condition at final visit in terms of change relative to the start of treatment (CGIC). At final visit, the participants CGIC will be categorized into a three point scale as: improvement: CGI response of very much improved, much improved or minimally improved; no change: CGI response of no change; worsening: CGI response of very much worse, much worse or minimally worse. Number of participants in each category is reported.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) Item Scores at Endpoint (up to Week 16) Baseline, Endpoint (up to Week 16) NPSI: participant-rated questionnaire to evaluate different symptoms of neuropathic pain. It includes 10 descriptors and 2 temporal items. Results reported for the 10 descriptors (burning, squeezing, pressure, electric shocks, stabbing, light touching of area, pressure of area, cold of area, pins and needles, tingling) quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) scale. Endpoint was the last observation for a participant assessed using specified imputation method.
Sleep Fragmentation Index (SFI) Baseline (Day -14 to 1), Week 1 through Week 4, Week 12 through Week 16, Endpoint (up to Week 16) SFI is a measure to quantify sleep restlessness. SFI calculated from analysis of the periods that participant was not moving (immobile bouts). It is number of immobile bouts that were exactly 1 minute long divided by total number of immobile bouts. Value ranges from 0-100 percent, with low number representing more restful sleep. SFI determined by actigraphy. Actigraphy was performed with an accelerometer that was worn on wrist like a watch. It was programmed to record movements while device was being worn. Endpoint was the last observation for a participant assessed using imputation method.
Medical Outcomes Study-Sleep Scale (MOS-SS): Number of Participants With Optimal Sleep Baseline, Endpoint (up to Week 16) MOS-SS: participant-rated 12 item questionnaire to assess constructs of sleep over past week. It included 7 subscales: sleep disturbance, snoring, awaken short of breath or with headache, sleep adequacy, somnolence, sleep quantity, optimal sleep, and 9 item index measures of sleep disturbance provide composite scores: sleep problems index. Participants responded whether their sleep was optimal or not optimal by choosing yes or no. Endpoint was the last observation for a participant assessed using imputation method.
Diagnostic Neuropathy Assessment Screening Absenteeism and Presenteeism Assessed by Work Productivity and Activity Impairment: Specific Health Problem (WPAI: SHP) Questionnaire Baseline, Week 16, 17 WPAI: 6-question participant rated questionnaire to determine the degree to which SHP affected work productivity while at work and affected activities outside of work. It assesses amount of absenteeism, presenteeism and daily activity impairment attributable to a HIV neuropathy pain. Question 2 and 3 assesses absenteeism as: Hours of work missed in past 7 days due to leg/foot pain or other reason, respectively. Question 4 assesses presenteeism as: Hours of work performed in past 7 days. A participant who had responded 'no' to question 1 regarding employment status reported hours of work and as this was a self-reported questionnaire the source data were included.
Productivity and Activity Impairment Assessed by Work Productivity and Activity Impairment: Specific Health Problem (WPAI: SHP) Questionnaire Baseline, Week 16, 17 WPAI: 6-question participant rated questionnaire to determine the degree to which SHP affected work productivity while at work and affected activities outside of work. It assesses amount of absenteeism, presenteeism and daily activity impairment attributable to a HIV neuropathy pain. Question 5 and 6 assesses: How much leg/foot pain affect productivity and daily activity, respectively in past 7 days? on 11-point scale, where 0 (not affected/no impairment) to 10 (completely affected/impaired).
Trial Locations
- Locations (63)
Hospital Nacional Guillermo Almenara Irigoyen
🇵🇪Lima, Peru
Ponce School of Medicine-CAIMED Center
🇵🇷Ponce, Puerto Rico
Hospital Nacional Dos de Mayo
🇵🇪Lima, Peru
Katedra Chorob Zakaznych i Hepatologii UMK w Toruniu CM w Bydgoszczy
🇵🇱Bydgoszcz, Poland
Ponce School of Medicine - Practice Group
🇵🇷Ponce, Puerto Rico
South East Asia Research Collaboration with Hawaii
🇹🇭Bangkok, Thailand
MediSynergy
🇿🇦Port Elizabeth, Eastern Cape, South Africa
Pretoria West Hospital
🇿🇦Pretoria West, Gauteng, South Africa
Drs Essack and Mitha
🇿🇦Johannesburg, Gauteng, South Africa
Innovir Institute
🇿🇦Gauteng, South Africa
Be Part Yoluntu Centre
🇿🇦Paarl, South Africa
Oddzial Diagnostyki i Terapii AIDS
🇵🇱Chorzow, Poland
Puerto Rico Clinical and Translational Research Consortium
🇵🇷Rio Piedras, Puerto Rico
Worthwhile Clinical Trials
🇿🇦Benoni, Gauteng, South Africa
Paarl Research Center
🇿🇦Paarl, South Africa
Dr J. Reddy's Surgery
🇿🇦Stanger, KwaZulu Natal, South Africa
Department of Neurology
🇿🇦Tygerberg, South Africa
Mzansi Ethical Research Centre
🇿🇦Middelburg, South Africa
Chris Hani Baragwanath Hospital, The Palliative Care Centre
🇿🇦Soweto, Gauteng, South Africa
Synapta Clinical Research Centre
🇿🇦Durban, South Africa
Border Diabetic Centre
🇿🇦East London, Eastern Cape, South Africa
Synexus SA Stanza Bopape Clinical Research Centre
🇿🇦Pretoria, Gauteng, South Africa
Clinical Research Unit, University of Pretoria
🇿🇦Pretoria, South Africa
Neurology unit, Department of Medicine,
🇹🇭Bangkok, Thailand
University of Toledo
🇺🇸Toledo, Ohio, United States
YR Gaitonde Centre for AIDS Research and Education
🇮🇳Chennai, Tamil Nadu, India
Southwest Center for HIV/AIDS
🇺🇸Phoenix, Arizona, United States
SW Center for HIV/AIDS
🇺🇸Phoenix, Arizona, United States
Arizona Research Center
🇺🇸Phoenix, Arizona, United States
AIDS Research Alliance of America
🇺🇸Los Angeles, California, United States
Anthony Mills, MD, Inc.
🇺🇸Los Angeles, California, United States
David Geffen School of Medicine at UCLA c/o NNAB
🇺🇸Los Angeles, California, United States
University of California San Diego
🇺🇸San Diego, California, United States
South Florida Medical Research
🇺🇸Aventura, Florida, United States
Neuroscience Consultants, LLC.
🇺🇸Aventura, Florida, United States
AIDS Research Consortium of Atlanta
🇺🇸Atlanta, Georgia, United States
Rehabilitation Institute of Chicago
🇺🇸Chicago, Illinois, United States
Midtown Neurology, PC
🇺🇸Atlanta, Georgia, United States
Neurology Specialists of Decatur Research Center
🇺🇸Decatur, Georgia, United States
The University of Texas Medical School at Houston
🇺🇸Houston, Texas, United States
Deenanath Mangeshkar Hospital and Research Centre
🇮🇳Pune, Maharashtra, India
Toga Laboratory
🇿🇦Johannesburg, Gauteng, South Africa
University of Witwatersrand-Clinical HIV Research Unit (CHRU)
🇿🇦Johannesburg, Gauteng, South Africa
University of Cape Town
🇿🇦Cape Town, Western Cape, South Africa
Stanford University Medical Center
🇺🇸Stanford, California, United States
Desert Medical Group, Inc. dba Desert Oasis Healthcare Medical Group
🇺🇸Palm Springs, California, United States
Wohlfeiler, Piperato & Associates, LLC
🇺🇸Miami Beach, Florida, United States
Providence Clinical Research
🇺🇸North Hollywood, California, United States
The Kinder Medical Group
🇺🇸Miami, Florida, United States
Meridien Research
🇺🇸Tampa, Florida, United States
University of Toledo Medical Center
🇺🇸Toledo, Ohio, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
University of Texas Physicians
🇺🇸Bellaire, Texas, United States
Amelia Court HIV Research Clinic
🇺🇸Dallas, Texas, United States
Asistencia Cientifica de Alta Complejidad
🇨🇴Bogota, Cundinamarca, Colombia
Riesgo de Fractura S.A
🇨🇴Bogotá, Cundinamarca, Colombia
Centro Instituto de Investigaciones Fundación Universitaria Sanitas
🇨🇴Bogota, Cundinamarca, Colombia
Instituto Dominicano de Estudios Virológicos - IDEV
🇩🇴Santo Domingo, Dominican Republic
Instituto Colombiano para el Avance de la Medicina- Santander S.A.S. - ICAMEDIC Santander S.A.S
🇨🇴Bucaramanga, Santander, Colombia
Mahavir Hospital and Research Centre
🇮🇳Hyderabad, Andhra Pradesh, India
Surakshaka Multispeciality Hospital
🇮🇳Hyderabad, Andhra Pradesh, India
Jaslok Hospital & Research Centre
🇮🇳Mumbai, Maharashtra, India
Infectious Disease Clinic
🇮🇳Ahmedabad, Gujarat, India