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

• ClinicalTrials.gov Identifier: NCT02607254
• Recruitment Status: Completed
• First Posted: November 18, 2015
• Results First Posted: October 4, 2018
• Last Update Posted: October 4, 2018
• Sponsor: Johns Hopkins University
• Collaborator: Pfizer
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Idiopathic Small Fiber Neuropathy	Drug: Pregabalin; Drug: Placebo	Phase 2

Detailed Description:

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Pregabalin in Treatment of Neuropathic Pain in Patients With Idiopathic Small Fiber Neuropathy
• Study Start Date: September 2015
• Actual Primary Completion Date: July 2018
• Actual Study Completion Date: July 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pregabalin Treatment phase; All patients will be initially treated with pregabalin in a single blind fashion	Drug: Pregabalin; 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.; Other Name: Lyrica
Experimental: Withdrawal phase; 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; Placebo will be given to the patients that are randomized to placebo during withdrawal phase.

Outcome Measures

Primary Outcome Measures :

1. Visual Analogue Score for Pain Intensity. [ Time Frame: Baseline, at 8 weeks after treatment phase and at 12 weeks for subjects completing the withdrawal phase ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins Hospital

Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

Johns Hopkins University

Pfizer

Investigators

• Principal Investigator: Mohammad Khoshnoodi, MD; Johns Hopkins University

  Study Documents (Full-Text)

Documents provided by Johns Hopkins University:

Study Protocol and Statistical Analysis Plan  [PDF] February 20, 2017

More Information

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT02607254
• Other Study ID Numbers: IRB00054498
• First Posted: November 18, 2015
• Results First Posted: October 4, 2018
• Last Update Posted: October 4, 2018
• Last Verified: October 2018

Additional relevant MeSH terms:

Neuralgia; Small Fiber Neuropathy; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Pregabalin; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anticonvulsants; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs