Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy

Study Overview
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Brief Summary
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Study to determine if pregabalin is more effective than placebo in treating subjects with nerve pain associated with HIV neuropathy.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Center Trial of Pregabalin Versus Placebo in the Treatment of Neuropathic Pain Associated With HIV Neuropathy.

Conditions
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HIV Infections, Peripheral Neuropathy

Intervention / Treatment
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* Drug: pregabalin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with confirmed diagnosis of HIV infection HIV-associated neuropathic pain (nerve pain) for at least 3 months prior to study start subjects with moderate to severe pain subjects on stable HIV and pain medications (some medications are not allowed to be taken while participating in the study). Exclusion Criteria: Pregnant or breast feeding females subjects using street drugs or alcohol abusers during the study subject's on anti-diabetic medications use of neuroregenerative agents or neurotoxic chemotherapeutic agents 3 months prior to study start and throughout the study use of neurotoxic drugs (other than D-drugs) within a month prior to study start and throughout the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: pregabalin<br>* 75mg BID (can be titrated up to 150mg BID on day 4 based on individual response and up to 300mg BID at the end of week 1, visit 3 and end of week 2, visit 4)<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline for Numerical Rating Scale (NRS) Pain Scores at Endpoint-LOCF (Last Observation Carried Forward) Relative to Baseline | Change from baseline in mean NRS-Pain scores at endpoint-LOCF. Daily pain scores were assessed on an 11-point numerical rating scale <(NRS)-Pain> ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline for MOS (Medical Outcomes Study)-Sleep Subscales and Sleep Problem Indices | Change from baseline in MOS-Sleep subscales & Sleep Problem Indices. Twelve item subject-rated questionnaire assessing sleep constructs. Scores range from 0 - 100 and higher scores reflect more impairment. Subscales sleep adequacy, quantity of sleep and optimal sleep low scores reflect impairment. | Baseline, Week 14 | 
| Change From Baseline for Hospital Anxiety and Depression Scale (HADS) Subscales | Change from Baseline in scale at endpoint: normal (score 0) to severe (score 21). | Baseline, Week 14 | 
| Change From Baseline for Modified Brief Pain Inventory-Short Form (mBPI-sf) Scores | Change from baseline to endpoint in the mBPI-sf to assess pain severity and pain interference with functional activities: 11-point scale ranging from no pain (0) to pain as bad as you can imagine (10) | Baseline, Week 14 | 
| Change From Baseline for NRS-Sleep Interference Scores | 11-point numerical rating scale ranging from 0 (did not interfere with sleep) to 10 (completely interfered [unable to sleep due to pain]) | Baseline, Week 14 | 
| Categorized Patient Global Impression of Change (PGIC) | The PGIC is a participant-rated instrument that measures change in the participants overall status on a 7-point scale. Scores range from 1 (very much improved) to 7 (very much worse). PGIC was evaluated using 3 categories of Improvement (Scores 1-3), No Change (Score 4), and Worsening (Scores 5-7). | Baseline, Week 14 | 
| Patient Global Impression of Change (PGIC) Rating | PGIC is a participant-rated instrument that measures change in the participants overall status on a 7-point scale. Scores range from 1 (very much improved) to 7 (very much worse). | Baseline, Week 14, Endpoint-LOCF | 
| Change in Neuropathic Pain Symptom Inventory (NPSI) Subscores and Total Intensity Scores | Change in mean score NPSI, questionnaire evaluates symptoms of neuropathic pain. 10 pain descriptors questions answered on an 11-point scale 0 (no pain)-10 (most intense pain imaginable). 2 items related to temporal pain assessed on 5-point scales. The NPSI derives 5 pain subscores & a total intensity score calculated from the 5 pain subscores | Baseline, Week 14 | 
| Change in Quantitative Assessment of Neuropathic Pain (QANeP) | Change in a quantitative assessment of the participants' neuropathic pain were on an 11-point scale ranging from 0 (no pain) to 10 (most intense pain imaginable). | Baseline, Week 14 | 
| Change in NRS-Sleep Interference Scores | Change in mean Pain-related sleep interference was assessed on an 11-point scale from 0 (did not interfere with sleep) to 10 (completely interfered [unable to sleep due to pain]). Weekly mean score was the sum of the daily diary scores divided by the number of diary entries during that week. | Baseline, Weeks 1-14 | 
| Shift in Hospital Anxiety and Depression (HADS) Subscales | Anxiety subscale analyzes generalized anxiety (anxious mood,restlessness, anxious thoughts, panic attacks). The depression subscale focuses on the state of lost interest and diminished pleasure response. A score of Normal = 0-7, Mild = 8-10, Moderate = 11-14, Severe = 15-21. | Baseline, Week 14 | 
| Change in Brief Pain Inventory-short Form (BPI-sf) Scores (The Worst Pain in the Past 24 Hours) | Change in mean BPI-sf, is a self-administered questionnaire to assess pain severity 0 (no pain to 10 (pain as bad as you can imagine) and pain interference 0 (does not interfere) to 10 (completely interferes) during a 24 hour period. The BPI-sf was used to derive the change from baseline in 4 pain severity questions & 7 pain interference questions. | Baseline, Weeks 1,2,6,10,14, Endpoint - LOCF | 
| Change in Brief Pain Inventory-sf Scores (The Least Pain in the Past 24 Hours) | Change in mean BPI-sf, is a self-administered questionnaire to assess pain severity 0 (no pain to 10 (pain as bad as you can imagine) and pain interference 0 (does not interfere) to 10 (completely interferes) during a 24 hour period. The BPI-sf was used to derive the change from baseline in 4 pain severity questions & 7 pain interference questions. | Baseline, Weeks 1,2,6,10,14, Endpoint-LOCF | 
| Change in Brief Pain Inventory-sf Scores (Average Level of Pain in the Past 24 Hours) | Change in mean BPI-sf, is a self-administered questionnaire to assess pain severity 0 (no pain to 10 (pain as bad as you can imagine) and pain interference 0 (does not interfere) to 10 (completely interferes) during a 24 hour period. The BPI-sf was used to derive the change from baseline in 4 pain severity questions & 7 pain interference questions. | Baseline, Weeks 1,2,6,10,14 and Endpoint | 
| Change in Brief Pain Inventory-sf Scores (How Much Pain Are You Having Right Now) | Change in mean BPI-sf, is a self-administered questionnaire to assess pain severity 0 (no pain to 10 (pain as bad as you can imagine) and pain interference 0 (does not interfere) to 10 (completely interferes) during a 24 hour period. The BPI-sf was used to derive the change from baseline in 4 pain severity questions & 7 pain interference questions. | Baseline, Weeks 1,2,6,10,14 and Endpoint | 
| Change in Brief Pain Inventory-sf Scores (During the Past 24 Hours, How Pain Has Interfered With Your General Activity) | Change in mean BPI-sf, is a self-administered questionnaire to assess pain severity 0 (no pain to 10 (pain as bad as you can imagine) and pain interference 0 (does not interfere) to 10 (completely interferes) during a 24 hour period. The BPI-sf was used to derive the change from baseline in 4 pain severity questions & 7 pain interference questions. | Baseline, Weeks 1,2,6,10,14 and Endpoint | 
| Change in Brief Pain Inventory-sf Scores (During the Past 24 Hours, How Pain Has Interfered With Your Mood) | Change in mean BPI-sf, is a self-administered questionnaire to assess pain severity 0 (no pain to 10 (pain as bad as you can imagine) and pain interference 0 (does not interfere) to 10 (completely interferes) during a 24 hour period. The BPI-sf was used to derive the change from baseline in 4 pain severity questions & 7 pain interference questions. | Baseline, Weeks 1,2,6,10,14 and Endpoint | 
| Change in Brief Pain Inventory-sf Scores (During the Past 24 Hours, How Pain Has Interfered With Your Walking Ability) | Change in mean BPI-sf, is a self-administered questionnaire to assess pain severity 0 (no pain to 10 (pain as bad as you can imagine) and pain interference 0 (does not interfere) to 10 (completely interferes) during a 24 hour period. The BPI-sf was used to derive the change from baseline in 4 pain severity questions & 7 pain interference questions. | Baseline, Weeks 1,2,6,10,14 and Endpoint | 
| Change in Brief Pain Inventory-sf Scores (During the Past 24 Hours, How Pain Has Interfered With Your Normal Work Including Both Work Outside the Home and Housework) | Change in mean BPI-sf, is a self-administered questionnaire to assess pain severity 0 (no pain to 10 (pain as bad as you can imagine) and pain interference 0 (does not interfere) to 10 (completely interferes) during a 24 hour period. The BPI-sf was used to derive the change from baseline in 4 pain severity questions & 7 pain interference questions. | Baseline, Weeks 1,2,6,10,14 and Endpoint | 
| Change in Brief Pain Inventory-sf Scores (During the Past 24 Hours, How Pain Has Interfered With Your Relations With Other People) | Change in mean BPI-sf, is a self-administered questionnaire to assess pain severity 0 (no pain to 10 (pain as bad as you can imagine) and pain interference 0 (does not interfere) to 10 (completely interferes) during a 24 hour period. The BPI-sf was used to derive the change from baseline in 4 pain severity questions & 7 pain interference questions. | Baseline, Weeks 1,2,6,10,14 and Endpoint | 
| Change in Brief Pain Inventory-sf Scores (During the Past 24 Hours, How Pain Has Interfered With Your Sleep) | Change in mean BPI-sf, is a self-administered questionnaire to assess pain severity 0 (no pain to 10 (pain as bad as you can imagine) and pain interference 0 (does not interfere) to 10 (completely interferes) during a 24 hour period. The BPI-sf was used to derive the change from baseline in 4 pain severity questions & 7 pain interference questions. | Baseline, Weeks 1,2,6,10,14 and Endpoint | 
| Change in Brief Pain Inventory-sf Scores (During the Past 24 Hours, How Pain Has Interfered With Your Enjoyment of Life) | Change in mean BPI-sf, is a self-administered questionnaire to assess pain severity 0 (no pain to 10 (pain as bad as you can imagine) and pain interference 0 (does not interfere) to 10 (completely interferes) during a 24 hour period. The BPI-sf was used to derive the change from baseline in 4 pain severity questions & 7 pain interference questions. | Baseline, Weeks 1,2,6,10,14 and Endpoint | 
| Shift Table NPSI (Neuropathic Pain Symptom Inventory) - Duration of Spontaneous Pain | Number of subjects reporting duration of spontaneous pain. The NPSI includes the temporal item for assessment of duration of spontaneous, ongoing and paroxysmal pain. Assessed using a 5-point specific categorical scale and refers to the past 24 hours at endpoint. | Baseline-Week 14 (Endpoint) | 
| Shift Table in NPSI (Neuropathic Pain Symptom Inventory)- Number of Pain Attacks | Number of subjects reporting pain attacks. The NPSI includes the temporal item for assessing the numbers of pain attacks. Assessed using a 5-point specific categorical scale and refers to the past 24 hours at endpoint. | Baseline-Week 14 (Endpoint) | 
| Change in Number of Pain Attacks Compared to Baseline - NPSI (Neuropathic Pain Symptom Inventory) | Change from baseline in the number of pain attacks at endpoint. The NPSI includes the temporal item for assessing the numbers of pain attacks. Assessed using a 5-point specific categorical scale and refers to the past 24 hours at endpoint. | Baseline, Week 14 | 
| Duration of Spontaneous Pain-NPSI (Neuropathic Pain Symptom Inventory) | Change from baseline to endpoint in the duration of spontaneous pain. The NPSI includes the temporal item for assessment of duration of spontaneous, ongoing and paroxysmal pain. Assessed using a 5-point specific categorical scale and refers to the past 24 hours at endpoint. | Baseline, Week 14 | 
| Gracely Pain Scale Score | The modified Gracely Pain Scale is a 13-point verbal rating scale based on sensory pain descriptors ranked by severity from nothing (rank = 0) to extremely intense (rank = 15). Subjects selected the verbal descriptors that best matched their average neuropathic pain during the last 24 hours prior to assessment. | Week 14 | 
| Quantitative Assessments of Neuropathic Pain (QANeP) Maximum Sensory Thresholds : Shift Table | Shift from baseline in maximum sensory thresholds (in grams representing the force equivalent of various sizes of von Frey filaments) as measured on QANeP. Improved - decrease in the maximum of the 3 trials at endpoint. Worsened - an increase. Note:Sensory Thresholds are the highest values of the 3 trials at baseline (Week=0) and endpoint (Week 14) | Baseline-Week 14 (Endpoint) | 
| Quantitative Assessments of Neuropathic Pain (QANeP) Median Sensory Thresholds : Shift Table | Shift from baseline in median sensory thresholds (designated as Weight) from 3 trials as measured on the QANeP. Improved - a decrease in the median of the three trials at endpoint. Worsened - an increase. Note: Sensory Thresholds are the highest values of the three Trials at both baseline (Week=0) and endpoint (Week 14). | Baseline-Week 14 (Endpoint) |