Topiramate in the Treatment of Sciatica

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00011804
First received: February 28, 2001
Last updated: March 3, 2008
Last verified: February 2005
  Purpose

This study will test the effectiveness of topiramate to treat pain caused by lumbar radiculopathy, or sciatica. Sciatica results from damage to the lumbar nerve roots, typically causing back pain and sharp, shooting pain down one or both legs. Although sciatica is common, there are no good treatments for it. Topiramate belongs to a group of medications commonly used to treat pain caused by nerve damage.

Patients between 18 and 75 years of age who have had sciatica pain daily for at least 3 months may be eligible for this study. (This is taken from the first paragraph of the Qualification Criteria in the consent form. The inclusion criteria on page 6 of the protocol say "low back pain of 3 months duration or longer present at least 5 out of 7 days a week" and signs and symptoms of lumbar radiculopathy. Which is correct?)

Participants will provide a medical history, as well as occupational and social information. They will undergo a standard neurological examination, including a test of cognitive (thinking) abilities, muscular function, reflexes and a sensory examination. The latter involves testing with a pin placed on the surface of the skin. Participants will also have routine blood tests and will fill out questionnaires on their daily functioning and psychological well being. Additional procedures may include magnetic resonance imaging (MRI) scans and possible referral to a psychiatrist for evaluation of depression or emotional difficulties.

This "cross-over" study consists of two parts. In one part, patients will receive topiramate and in the other, an active placebo. An active placebo is a drug that does not work for the problem being studied but whose side effects are like those of the test drug. Diphenhydramine (Benadryl) is the active placebo used in this study. Diphenhydramine is an allergy medication with very mild side effects, such as drowsiness. During both parts of the study-topiramate and placebo-patients will keep a daily log in which they rate their pain, record other procedures they undergo, such as injections and manipulations, and record medication side effects.

In the first week of the study, patients will remain on their current medications and record pain levels once a day. After the first week, they will begin taking the study drugs-either topiramate in increasing doses ranging from 50 to 400 mg. or diphenhydramine in doses ranging from 6.25 to 50 mg. The drug doses will be increased gradually over 4 weeks to minimize possible side effects. Increases will continue until the maximum tolerated dose is reached. Patients will continue on the highest tolerated dose for two weeks and then be tapered off gradually over 12 days. They will remain off drugs completely for a 2-day washout period and then begin the next treatment. Those who took topiramate for the first part will take diphenhydramine for the second part and vice versa.

A study nurse will call patients twice a week throughout the study to check for problems and answer questions. A physician will see patients 6 weeks after the start of each treatment. During the last visit, at the end of the study, patients will repeat the questionnaires they filled out at the beginning of the study. Patients and their doctors will be informed of the medications that were effective in each individual's care.


Condition Intervention Phase
Sciatica
Drug: Topiramate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
Official Title: Topiramate in the Treatment of Sciatica

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 65
Study Start Date: February 2001
Estimated Study Completion Date: February 2005
Detailed Description:

Irritation or damage to lumbar nerve roots referred to as lumbar radiculopathy or sciatica is a very common clinical entity with a lifetime prevalence of 1-3% in the adult population. Lumbar radiculopathy typically causes back pain and sharp, shooting pain in the leg(s). Despite its prevalence and disabling characteristics, sciatica has never been selectively studied in drug trials. We propose to study the anti-epileptic drug topiramate, which combines multiple potential analgesic actions including sodium channel blockade, GABA agonist-like effects and AMPA/kainate glutamate receptor blockade. Patients will include men and women of all ethnic backgrounds between the ages of 18 and 75 who have had signs and symptoms of sciatica for 3 months or more.

The design is a double-blind, two period cross-over study comparing topiramate to placebo. Patients will be called twice a week to individually titrate doses of topiramate towards a maximum of 800 mg per day and monitor side effects. The primary outcome measures in this study will be the daily pain scores in the low back, in the leg and combined. Patients' quality of life and activities of daily living will be secondary outcome measures as assessed by the SF 36, Oswestry, and Beck questionnaires. Sixty five patients will be enrolled in this study and the duration of the study will be 17 weeks, including one week baseline, four week escalation, two week maintenance and two week wash out for topiramate and placebo respectively.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

Low back pain of 3 months duration or longer present at least 5 out of 7 days a week are eligible.

Age between18-75 at the start of the study.

Men and women of all ethnicities.

Signs and symptoms of lumbar radiculopathy.

Ability to understand the study measures and mentally capable of giving consent to participate in the study.

Willingness to refrain from making changes in non-study medications taken for sciatica.

Patients with failed back syndrome who satisfy the following criteria:

Presence of low back pain and pain in one or both lower extremities (buttock and below) for 3 months or greater and at least one of the following:

  1. Sharp and shooting pain below the knee in one or both legs.
  2. Electromyographic evidence of 4th or 5th lumbar roots (L4 or L5) / first sacral root (S1) irritation on the affected side.
  3. Imaging (MRI or CT/Myelogram) evidence of nerve root compression in lower lumbar region on the affected side.
  4. Evidence of decreased/absent ankle reflex on the affected side.
  5. Evidence of weakness of muscles below the knee on the affected side.
  6. Evidence of sensory loss in L5/S1 distribution on the affected side.

Pain level of at least 4/10 on average on a scale of 0 to 10 for the past month.

EXCLUSION CRITERIA:

Hepatic and renal dysfunction (liver function tests: ALT/AST greater than 1.2 times upper limit of normal; Creatinine greater than 1.5 times upper limits of normal).

Pregnancy or lactation.

History of seizures.

Presence of pain of greater intensity in any other location than the low back or the leg.

History of narcotic abuse and/or drug or alcohol abuse in the past year.

History of fibromyalgia.

History of spinal unstability.

Cognitive impairment such that the individual is unable to give informed consent, complete study data collection tools or required study visits.

Unwillingness to use adequate contraception excluding oral contraceptive medications (such as barrier methods with spermacide simultaneously) for women.

Presence of other medical condition presenting with numbness and pain in lower extremities, such as diabetic polyneuropathy and peripheral vascular disease.

Allergy to topiramate.

Participants must not use digoxin, probenicid, carbonic anhydrase inhibitors given their possible drug interaction with topiramate.

History of nephrolithiasis.

Allergy to diphenhydramine.

History of narrow angle glaucoma.

History of asthma and COPD.

Urinary retention of any etiology.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00011804

Locations
United States, Maryland
National Institute of Dental And Craniofacial Research (NIDCR)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00011804     History of Changes
Other Study ID Numbers: 010105, 01-D-0105
Study First Received: February 28, 2001
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Low Back Pain
Lumbar Radiculopathy
Anticonvulsants
Neuropathic Pain
Analgesia
Sciatica

Additional relevant MeSH terms:
Sciatica
Mononeuropathies
Nervous System Diseases
Neuralgia
Neurologic Manifestations
Neuromuscular Diseases
Pain
Peripheral Nervous System Diseases
Sciatic Neuropathy
Signs and Symptoms
Topiramate
Anti-Obesity Agents
Anticonvulsants
Central Nervous System Agents
Neuroprotective Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014