Pilot Study Of Pregabalin And Prediction Of Treatment Response In Patients With Postherpetic Neuralgia

Study Overview
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Brief Summary
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The primary objective is to explore whether sensory symptom cluster analysis is useful for predicting treatment response in Postherpetic Neuralgia.

Detailed Description
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The study was stopped on 26 April 2013 due to feasibility issues (low enrollment) not safety. The overall risk-benefit of Lyrica has not changed at all due to termination of this trial. Only 9 of the 150 patients were enrolled into the trial, so we are unable to get adequate results from this study.

Official Title
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A Phase 4 Multicenter, Open-Label, Pilot Study Of Pregabalin And Prediction Of Treatment Response In Patients With Postherpetic Neuralgia

Conditions
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Postherpetic Neuralgia

Intervention / Treatment
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* Drug: pregabalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have pain present for more than 3 months after the healing of the herpes zoster skin rash. At screening (V1) and baseline (V2), subjects must have a score of >=4 on the Numeric Rating Scale for Pain (1 week recall period). At baseline (V2), at least 4 pain diaries must be completed satisfactorily within the last 7 days and the average pain score must be >=4. Exclusion Criteria: Subjects having other severe pain that may confound assessment or self evaluation of the pain due to PHN. Neurolytic or neurosurgical therapy for Postherpetic Neuralgia Skin conditions in the affected dermatome that could alter sensation.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pregabalin (300-600 mg/day; 150 mg/day starting dose)<br> | Drug: pregabalin<br>* Pregabalin Capsules (150 mg - 600mg), Dose titration (4 weeks) and fixed dose (2 weeks) for a 6 week treatment period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Daily Pain Diary (Numerical Rating Scale, NRS) Mean Pain Score at the End of the Study (Week 6). | The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. | Baseline, Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropathic Pain Symptom Inventory (NPSI) at All Visits. | NPSI: participant rated questionnaire to evaluate different symptoms of neuropathic pain (dimensions: 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. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicates a greater intensity of pain. | All visits | 
| Proportion of Phenotypes Within the 30% and 50% Responder Groups at Baseline and Week 6. | To explore whether sensory symptom cluster analysis is useful for predicting treatment response in paticipants with PHN, identification of the phenotype was initially required of all participants using three different approaches (with or without the baseline PHQ-8, GAD-7 Pain Related Sleep Interference Score Scale, PCS): 1. PainDETECT at baseline, 2. PainPREDICT at baseline, 3. NPSI at baseline. Then for each of the above phenotypes the distribution of the pregabalin responders (using 30% and 50%) were to be compared. | Baseline, Week 6 | 
| Patient Global Impression of Change (PGIC) at Week 6/Early Termination. | 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). | Week 6/Early Termination | 
| Proportions of Participants With >/=30% and >/=50% Pain Reduction Based on Daily Pain Diary at Baseline and Week 6. | The daily pain diary consists of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants describe their pain during the previous 24 hours by choosing the appropriate number between 0 and 10. Self-assessment is performed daily at bedtime on a telephone via interactive voice response system (IVRS). The endpoint mean pain score is defined as the mean of the last 7 daily diary pain ratings while taking study medication in the open-label phase. Daily pain IVRS diaries were completed daily at bedtime from Visit 1 (Screening) through Visit 7/Early Termination. Participants were asked to complete their first IVRS daily at bedtime on the morning after Visit 1. | Baseline, Week 6 | 
| Proportion of Participants Within Each Phenotype Group as Determined by Sensory Symptom Clustering Using the PainPREDICT, PainDETECT and Neuropathic Pain Symptom Inventory at Baseline and Week 6. | To explore whether sensory symptom cluster analysis is useful for predicting treatment response in paticipants with PHN, identification of the phenotype was initially required of all participants using three different approaches (with or without the baseline PHQ-8, GAD-7 Pain Related Sleep Interference Score Scale, PCS): 1. PainDETECT at baseline, 2. PainPREDICT at baseline, 3. NPSI at baseline. | Baseline, Week 6 | 
| Patient Health Questionnaire-8 (PHQ-8) at Baseline and Week 6; Generalized Anxiety Disorder-7 (GAD-7) at Screening, Visit 2 (Week 0) and Week 6/Early Termination. | The PHQ-8 is a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders. The PHQ-9 is the depression module, which scores each of the 9 DSM-IV criteria as 0 (not at all) to 3 (nearly every day). The PHQ-8 is a validated subset of the PHQ-9, which comprises the first 8 items of the measure. The GAD-7 is a 7-item questionnaire that assesses anxiety. Participants respond as to how each item applies to them on a 4 point response scale. The higher the score, the more severe the anxiety. | Screening, Visit 2 (Week 0) and Week 6/Early Termination | 
| Brief Pain Inventory (BPI sf) at Visit 2 (Week 0) and Week 6. | The Brief Pain Inventory-Short Form (BPI-sf) consists of 5 questions. Questions 1, 2, 3, and 4 measure pain on an 11-point scale from 0 (no pain) to 10 (worst pain possible). | Visit 2 (Week 0), Week 6 | 
| Patient Catastrophizing Scale (PCS) at Visit 2 (Week 0) and Week 6. | The PCS is a 13-item self report instrument and requires a Grade 6 reading level and has been translated into 12 languages. It instructs participants to reflect on past experience of pain and indicate their experience using a 5-point scale. The PCS was designed for research on catastrophizing and pain experience. Catastrophizing is associated with heightened pain and is an exaggerated negative mental set brought to bear during actual or anticipated painful experience. It is a multidimensional construct compromising elements of rumination, magnification, and helplessness and its factor structure has been replicated. It has a total score and three subscale scores (score range of 0-52). | Visit 2 (Week 0), Week 6 | 
| Pain NRS Score; 1 Week Recall Period. | The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. | 1 Week | 
| Short Form 12v2 Health Survey (SF 12v2) at Visit 2 (Week 0), and Week 6/Early Termination. | The Short-Form 12 Health Survey (SF-12v2) is a self-administered, validated questionnaire that measures each of the following 8 health aspects: Physical functioning, role limitations due to physical problems, social functioning, bodily pain, mental health, role limitations due to emotional problems, vitality, and general health perception over the past week. Higher scores indicate a better health-related quality of life. | Visit 2 (Week 0), and Week 6/Early Termination | 
| Change From Baseline to End of the Study (Week 6) in the Daily Sleep Interference Diary (NRS) Mean Pain Score. | The pain-related sleep interference item rating scale is scored on an 11-point numeric rating scale (NRS-Sleep). It is self-administered by the participant in order to rate how pain has interfered with their sleep during the past 24 hours, ranging from 0 (pain does not interfere with sleep) to 10 (completely interferes (unable to sleep due to pain). Participants are to describe how their pain has interfered with their sleep during the past 24 hours by choosing the appropriate number on the numeric rating scale. | Baseline, Week 6 |