This study will assess the safety and effectiveness of the drug gabapentin in reducing pain associated with primary fibromyalgia.

Condition	Treatment or Intervention	Phase
Fibromyalgia	Drug: gabapentin	Phase II Phase III

Fibromyalgia, a chronic musculoskeletal pain disorder of unknown etiology, is characterized by widespread musculoskeletal pain, fatigue, and multiple tender points; the disease affects 3 to 6 million Americans. A person is considered to have fibromyalgia if he or she has widespread pain in combination with tenderness in at least 11 of 18 specific tender point sites.

Treatment of fibromyalgia requires a comprehensive approach and includes aerobic exercise, heat and massage, antidepressant medications, and relaxation. Gabapentin, a medication used to treat seizures, has been shown to work on pain transmission pathways and may relieve the pain associated with fibromyalgia. This study will assess the efficacy of gabapentin in reducing pain severity in fibromyalgia as measured by the average pain item of the Brief Pain Inventory (BPI) score.

Patients will be randomized to receive gabapentin or placebo. The gabapentin dose will be titrated for persisting symptoms and as tolerated during the first 6 weeks of the study, reaching final doses between 1800 mg/day and 2400 mg/day. Patients will then continue on the final dose for the remaining 6 weeks of the study. Following completion of the 12 week treatment phase, patients will be tapered off of the medication over 1 week.

The effectiveness of gabapentin will be assessed using the BPI. The BPI is a self-administered questionnaire that measures the severity of pain and the interference of pain on function over the past 24 hours. Other assessments will include the total Fibromyalgia Impact Questionnaire (FIQ) score; six 11-point Likert-type scales in the FIQ that measure pain, fatigue, morning tiredness, stiffness, anxiety, and depression; the mean tender point pain threshold; Clinical Global Impression of Severity (CGI-Severity); Patient Global Impression of Improvement (PGI-Improvement); the Short-form McGill Pain Questionnaire (SF-MPQ); the Medical Outcomes Study Short Form-36 (SF-36); the Montgomery Asberg Depression Rating Scale (MADRS); and the Medical Outcomes Sleep Scale (MOS-Sleep).

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Primary fibromyalgia as defined by the American College of Rheumatology (ACR)
• Score > 4 on the average pain item of the BPI at screening
• Ability to understand and cooperate with study procedures
• Acceptable methods of contraception

Exclusion Criteria:

• Unwillingness or inability to provide written informed consent.
• Lifetime history of psychosis, hypomania or mania, epilepsy, or dementia
• History of seizures or status epilepticus
• DSM-IV diagnosis of alcohol or substance dependence with the exception of nicotine dependence within 6 months prior to screening visit
• A positive urine drug screen for any substances of abuse or excluded medication. (NOTE: If the participant has a positive drug screen at Visit 1 for an excluded medication that may not have had an adequate wash-out period, a retest may be performed prior to Visit 2. If the retest is positive, the participant will be excluded.)
• Serious suicide risk
• Treatment refractory in the opinion of study official
• Pregnant or breastfeeding
• Clinically unstable medical or psychiatric condition that could interfere with the absorption, metabolism, excretion, or safety of gabapentin or interfere with the assessment of disease severity
• Thyroid-stimulating hormone (TSH) concentrations outside the range of 0.30-8.0 UlU/mL. (NOTE: Participants who have been on a stable dose of thyroid supplementation for at least the past 3 months, have medically appropriate TSH values, and are clinically euthyroid may participate in the study.)
• Any screening laboratory assay that is outside of the local laboratories’ normal range by more than 20% or is deemed to be a clinically significant abnormality by the investigator, with the exception of liver function tests (AST, ALT, alkaline phosphatase) which must be within 1.5 X upper limit of normal
• Inability to exclude traumatic injury, regional or structural rheumatic disease, or infectious arthropathy as the etiology of their relevant symptoms and that would interfere with interpretation of outcome measures (e.g., osteoarthritis, bursitis, tendonitis)
• History of an autoimmune disease or inflammatory arthritis, such as systemic lupus erythematosis (SLE) or rheumatoid arthritis (RA).
• An abnormal Westergren erythrocyte sedimentation rate (e.g., ESR > 40 mm/min)
• An abnormal antinuclear antibody (ANA > 1:160) or rheumatoid factor (RF >15 IU/ml)
• Treatment with a monoamine oxidase inhibitor, tricyclic, SSRI antidepressant (with the exception of fluoxetine), or lithium within 2 weeks prior to beginning study medication
• Treatment with fluoxetine within 30 days prior to beginning study medication
• Treatment with analgesic medication (with the exception of acetaminophen and over-the-counter NSAIDs) within 1 week prior to beginning study medication
• Treatment with any other excluded medications that cannot be discontinued at the screening visit (see Table 2 for a list of excluded medications)
• Previous treatment with gabapentin
• Previous treatment with pregabalin
• Treatment with any other investigational medications within 30 days prior to screening

Penny Brooks, BA      513-475-8115    catherine.brooks@uc.edu
Carrie L. Gibson, BA      513-475-8113    carrie.gibson@uc.edu

Massachusetts
      McLean Hospital/Harvard Medical School (must live in the Boston, MA area), Belmont,  Massachusetts,  02478,  United States; Recruiting
      Newton-Wellesley Hospital (must live in the Boston, MA area), Newton,  Massachusetts,  02462,  United States; Recruiting
Ohio
      University of Cincinnati College of Medicine, Department of Psychiatry (must live in the Cincinnati, OH area), Cincinnati,  Ohio,  45219,  United States; Recruiting

Study chairs or principal investigators

Lesley M. Arnold, MD,  Principal Investigator,  University of Cincinnati   

Study ID Numbers:  NIAMS-089; 1N01 AR22264
Record last reviewed:  September 2004
Record first received:  March 28, 2003
ClinicalTrials.gov Identifier:  NCT00057278
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-11-08