Evaluation of Pregabalin in Idiopathic Small Fiber Neuropathy

NCT ID: NCT00787462

Last Updated: 2017-08-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2013-02-28

Brief Summary

Idiopathic Small Fiber Neuropathy (called SFN for short), is a condition where nerves that sense pain have become damaged, and often painful. SFN pain is common, and it can affect sleep, memory, health and overall quality of life.

Pregabalin is a drug commonly used to treat painful conditions, like nerve pain. It has been available to doctors for many years, and many studies have been performed to evaluate its effectiveness. In these studies, pregabalin has been shown to be very effective in the treatment of nerve pain, with fewer side effects than many other medications currently available. The purpose of the study is to determine if pregabalin relieves pain more effectively than a pill containing no medication (called a placebo). The study will also investigate any side effects as well as the effectiveness and safety of the medication.

Detailed Description

Painful small fiber sensory neuropathy (SFN) is relatively common and a disabling medical condition. It is the most common type of painful sensory neuropathy in patients older than 50 years of age. It is defined as a neuropathy that exclusively or predominantly affects the A-δ (small myelinated) and nociceptive C (unmyelinated) nerve fibers and their functions. The neuropathic pain associated with SFN is described by the patients as burning ("feet are on fire"), sharp ("knife-like, jabbing or pins and needles"), shooting, and aching pain in the toes and feet. The feet are described as tingling, numb, or feeling tight, wooden or dead. The pain is disabling and often exacerbated at night interfering and disrupting the sleep pattern. Allodynia and cramps may also occur. Some patients also describe pressure induced pain in their feet with standing and walking. The autonomic nerves may be involved leading to increased or decreased sweating, facial flushing, skin discoloration and erectile dysfunction in up to 40% of males. On examination there is a dramatic mismatch between the symptoms and observable deficits in SFN. Only abnormal findings are the loss of pinprick and temperature sensations in feet that may extend up to the knees. Touch sensation may be diminished but other sensations are usually preserved. By definition, patients with SFN are allowed to have minor involvement of large fibers distally with reduced vibration in toes but the ankle reflexes are usually preserved.

This study will be of a crossover design thus minimizing the number of subjects needed. Each patient will act as his/her own control. Previous studies of pregabalin have shown that the desired effect is achieved by eight weeks of treatment. Therefore each patient will start on either placebo or pregabalin. They will be assessed on this treatment arm for eight weeks. There will be a two-week drug tapering and washout period before switching treatments, followed by re-assessment for an additional eight weeks. This design minimizes the amount of time that the patient will be treated with placebo.

Conditions

Small-Fiber Neuropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Active

Available as 75 mg capsules. Subjects will begin Phase 1 treatment on either pregabalin (or placebo) 75mg BID (1 capsule BID) for one week then increasing to 150mg BID or placebo (2 capsules BID) for a further 7 weeks. During this period patients will be allowed to taper the drug to 225mg a day (75mg in am, 150mg in pm) or (75mg BID) if they develop significant adverse effects on the higher dose. After 8 weeks Phase 1 treatment subjects will taper study medication to 75mg BID or placebo (1 capsule BID) for 7 days and then continue taking placebo (1 capsule) for 7 additional days prior to the crossover. After the taper and washout, Phase 2 will begin using the alternate treatment and will follow the same dosing regime as Phase 1 for the remaining 10 weeks.

Group Type: ACTIVE_COMPARATOR

Pregabalin

Intervention Type: DRUG

Available as 75 mg capsules. Subjects will begin Phase 1 treatment on either pregabalin (or placebo) 75mg BID (1 capsule BID) for one week then increasing to 150mg BID or placebo (2 capsules BID) for a further 7 weeks. During this period patients will be allowed to taper the drug to 225mg a day (75mg in am, 150mg in pm) or (75mg BID) if they develop significant adverse effects on the higher dose. After 8 weeks Phase 1 treatment subjects will taper study medication to 75mg BID or placebo (1 capsule BID) for 7 days and then continue taking placebo (1 capsule) for 7 additional days prior to the crossover. After the taper and washout, Phase 2 will begin using the alternate treatment and will follow the same dosing regime as Phase 1 for the remaining 10 weeks.

Placebo

Available as 75 mg capsules. Subjects will begin Phase 1 treatment on either pregabalin (or placebo) 75mg BID (1 capsule BID) for one week then increasing to 150mg BID or placebo (2 capsules BID) for a further 7 weeks. During this period patients will be allowed to taper the drug to 225mg a day (75mg in am, 150mg in pm) or (75mg BID) if they develop significant adverse effects on the higher dose. After 8 weeks Phase 1 treatment subjects will taper study medication to 75mg BID or placebo (1 capsule BID) for 7 days and then continue taking placebo (1 capsule) for 7 additional days prior to the crossover. After the taper and washout, Phase 2 will begin using the alternate treatment and will follow the same dosing regime as Phase 1 for the remaining 10 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Available as 75 mg capsules. Subjects will begin Phase 1 treatment on either pregabalin (or placebo) 75mg BID (1 capsule BID) for one week then increasing to 150mg BID or placebo (2 capsules BID) for a further 7 weeks. During this period patients will be allowed to taper the drug to 225mg a day (75mg in am, 150mg in pm) or (75mg BID) if they develop significant adverse effects on the higher dose. After 8 weeks Phase 1 treatment subjects will taper study medication to 75mg BID or placebo (1 capsule BID) for 7 days and then continue taking placebo (1 capsule) for 7 additional days prior to the crossover. After the taper and washout, Phase 2 will begin using the alternate treatment and will follow the same dosing regime as Phase 1 for the remaining 10 weeks.

Interventions

Pregabalin

Available as 75 mg capsules. Subjects will begin Phase 1 treatment on either pregabalin (or placebo) 75mg BID (1 capsule BID) for one week then increasing to 150mg BID or placebo (2 capsules BID) for a further 7 weeks. During this period patients will be allowed to taper the drug to 225mg a day (75mg in am, 150mg in pm) or (75mg BID) if they develop significant adverse effects on the higher dose. After 8 weeks Phase 1 treatment subjects will taper study medication to 75mg BID or placebo (1 capsule BID) for 7 days and then continue taking placebo (1 capsule) for 7 additional days prior to the crossover. After the taper and washout, Phase 2 will begin using the alternate treatment and will follow the same dosing regime as Phase 1 for the remaining 10 weeks.

Intervention Type: DRUG

Placebo

Available as 75 mg capsules. Subjects will begin Phase 1 treatment on either pregabalin (or placebo) 75mg BID (1 capsule BID) for one week then increasing to 150mg BID or placebo (2 capsules BID) for a further 7 weeks. During this period patients will be allowed to taper the drug to 225mg a day (75mg in am, 150mg in pm) or (75mg BID) if they develop significant adverse effects on the higher dose. After 8 weeks Phase 1 treatment subjects will taper study medication to 75mg BID or placebo (1 capsule BID) for 7 days and then continue taking placebo (1 capsule) for 7 additional days prior to the crossover. After the taper and washout, Phase 2 will begin using the alternate treatment and will follow the same dosing regime as Phase 1 for the remaining 10 weeks.

Intervention Type: DRUG

Other Intervention Names

Lyrica; Visually Identical Placebo

Eligibility Criteria

Inclusion Criteria

• A diagnosis of idiopathic SFN (based on clinical and electrodiagnostic criteria).
• Each day for 7 days prior to Visit 2 (Washout) they must complete a modified Quadruple Visual Analogue Scale₁ showing moderate to severe pain (i.e. a daily mean rating score of ≥ 4).
• As the safety of pregabalin in pregnancy has not been established, females of childbearing potential must have a negative βHCG serum and agree to practice acceptable birth control methods.
• All subjects must have screening laboratory values that are within normal limits or abnormal values that are deemed not clinically significant by the Principle Investigator.

Exclusion Criteria

• Have a psychological or psychiatric condition that may hinder their ability to provide important information
• History of psychosis, drug or alcohol abuse history within the last year
• Malignancy within the last 2 years (except skin cancer)
• Clinically significant conditions (including but not limited to cardiovascular or hepatic diseases), and seizure disorders.
• Subjects with an abnormal 2-hour glucose tolerance test (i.e., glucose >7.8 mmol/l) will be excluded under "clinically significant conditions" as stated above.
• May not have participated in a previous trial of pregabalin, have a history of intolerance or hypersensitivity to pregabalin.
• Patients with renal impairment (CrCl < 60 ml/min) will be excluded.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Capital Health, Canada

OTHER

Sponsor Role: collaborator

University of Alberta

OTHER

Sponsor Role: lead

Responsible Party

Zaeem Siddiqi

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zaeem A Siddiqi, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

MD, Profesor of Medicine, Neurology

Locations

University of Alberta Hospital

Edmonton, Alberta, Canada

Countries

Canada

Other Identifiers

ZAS-2007-HC-01

Identifier Type: -

Identifier Source: org_study_id