Efficacy and Safety of Pregabalin in Treatment of Neuropathic Pain in Patients With Idiopathic Small Fiber Neuropathy

Study Overview
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Brief Summary
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The purpose of this study is to assess safety and efficacy of treatment with pregabalin in patients with idiopathic small fiber neuropathy proven by skin biopsy.This is an enriched enrollment randomized withdrawal study that comprises 4 phases: a screening and selection phase, a washout period from previous pain medication for enriched enrollment, an 8 week single blind pregabalin treatment phase; and a 4 week randomized withdrawal phase.

Detailed Description
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Patients who show any increase in their pain intensity score during the washout phase will be eligible for the single blind pregabalin treatment phase. Patients who respond to pregabalin, with at least 1 point improvement in neuropathic pain from baseline at the end of the single blind pregabalin treatment phase and meeting all other study requirements are considered eligible for participation in the withdrawal phase. These eligible patients are randomly assigned (1:1) to continue pregabalin or to be switched to placebo for a comparison of pregabalin efficacy and safety. Patients who have a worsening of average pain relative to the last week of the single blind pregabalin treatment period by more than one point and average pain level > =4 will be considered to have a loss of therapeutic response (LTR).

Official Title
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Efficacy and Safety of Pregabalin in Treatment of Neuropathic Pain in Patients With Idiopathic Small Fiber Neuropathy

Conditions
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Idiopathic Small Fiber 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 idiopathic predominate-small fiber neuropathy Subject must have chronic peripheral neuropathic pain for more than 3 months A score >3 and <8 on Pain intensity scale for pain in prior week at first visit; Show increase in pain intensity scores during the wash off period; Age older than 18 years; Exclusion Criteria: Subjects with large-fiber predominant neuropathy Subjects with HIV infection, trigeminal neuralgia (TGN), toxic neuropathy (e.g. chemotherapy exposure), paraneoplastic neuropathy, mono-gammopathy, inflammatory neuropathy, celiac disease, systemic lupus, peripheral vascular disease, connective tissue disorders, hepatitis C, Fabry disease, and diabetes; Subjects with uncontrolled thyroid or B12 disorders Subjects with Complex Regional Pain Syndrome Allergy to Pregabalin Subjects at risk of suicide or self harm Subjects with any clinically unstable cardiovascular, hematological, autoimmune, endocrine, renal, hepatic, renal, respiratory, or gastrointestinal disease; epilepsy, symptomatic peripheral vascular disease including intermittent claudication, pernicious anemia, untreated hypothyroidism, venous insufficiency, or spinal stenosis. History of known analgesic, alcohol or illicit drug abuse within 12 months of first visit; Pregnant females; breastfeeding females.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pregabalin Treatment phase<br>All patients will be initially treated with pregabalin in a single blind fashion | Drug: Pregabalin<br>* Pregabalin will be given to the patients, starting at 75 mg BID and increased weekly to reach 225 mg BID for 8 weeks. During withdrawal phase, dose of pregabalin will be kept the same for patients who are randomized to the pregabalin withdrawal group.<br>* Other names: Lyrica;|
| Experimental: Withdrawal phase<br>After finishing the treatment phase, some patients will be randomized to the placebo or continue on pregabalin for the 4 weeks of withdrawal phase. | Drug: Placebo<br>* Placebo will be given to the patients that are randomized to placebo during withdrawal phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analogue Score for Pain Intensity. | The primary outcome is change in visual analogue score for pain, with 0 being no pain at all and 10 being the most severe pain and a higher score meaning more pain, after 8 weeks of treatment phase and 4 weeks of randomized withdrawal phase. | Baseline, at 8 weeks after treatment phase and at 12 weeks for subjects completing the withdrawal phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Pain Inventory (BPI sf); | Brief pain inventory is a scoring system for average pain intensity on scale of 0-10 with higher number meaning more pain. | Baseline, at 8 weeks after treatment phase and at 12 weeks for subjects completing the withdrawal phase | 
| Sleep Quality as Assessed by Daily Sleep Interference Rating Scale (SIRS); | a scoring system describing sleep quality between 0-10 with 0 having no problem with sleep and 10 not being to sleep at all. | Baseline, at 8 weeks after treatment phase and at 12 weeks for subjects completing the withdrawal phase | 
| Patient Global Impression of Change (PGIC); | patient assign a number between 1-7 to the level of improvement, 1 showing substantial improvement and 7 showing no improvement at all. | At 8 weeks after treatment phase and at 12 weeks for subjects completing the withdrawal phase |