Combining N-of-1 Trials to Assess Fibromyalgia Treatments
Condition: Fibromyalgia
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes
Study type: Interventional
Phase: Phase 4

Summary: 
      This study will compare the effectiveness of combination therapy with the drugs amitriptyline
      and fluoxetine (AM+FL) and amitriptyline (AM) alone in the treatment of people with
      fibromyalgia. Doctors will treat each study participant with both AM + FL and AM alone for 6
      weeks at a time. The study uses a method that combines results from treatment of individual
      patients to assess overall treatment effectiveness and help individual patients and their
      physicians with their treatment decisions. This study will also help compare the results of
      community-based studies (studies involving private doctors) and studies based at clinical
      research centers.
    

Detailed description: 
      This study will use the combined N-of-1 method to compare the effectiveness of the
      combination therapy amitriptyline and fluoxetine (AM+FL) versus amitriptyline (AM) alone in
      patients with fibromyalgia (FM). It will also compare community-based and center-based trial
      results. We will ask community-based, board-certified rheumatologists to participate as
      investigators and we will also carry out a center-based study (at Newton-Wellesley Hospital).
      Physicians will ask patients meeting eligibility criteria to participate in this study and
      undergo an N-of-1 trial.

      Each N-of-1 trial will consist of three paired crossover periods (each 6-weeks long) during
      which the patient will receive either AM + placebo (placebo every morning and AM 25 mg at
      night) or combination treatment AM+FL (FL 20 mg in the morning and AM 25 mg at night). The
      dispensing pharmacy will carry out paired randomization.

      We will assess patient evaluations and outcome measures at baseline prior to trial, at the
      end of each treatment period, and 3 months after completion of the N-of-1 trial. In addition,
      at baseline, we will obtain demographic information, an electrocardiogram, and baseline blood
      tests. We may ask patients to have additional blood tests at the period evaluations. We will
      also do a pregnancy test for all women of child-bearing age enrolling in the study. The main
      study outcome measure will be the Fibromyalgia Impact Questionnaire (FIQ). Additional
      measures will include the Visual Analog Scales (VAS) for pain, sleep, global well-being;
      Physician VAS for global well-being; and tender-point score.

      We will analyze the results of the N-of-1 trials in two ways: (1) using only the individual
      patient's results (classic one-sided t-test) and (2) using the patient's results in
      combination with the results of other patients who underwent similar trials (the combined
      N-of-1 approach). To obtain the latter information, we will include each patient's results
      for the collective analysis. We will provide these results back to the physicians and will
      record the final treatment decisions the physicians reach with their patients. In addition,
      we will ask both physicians and patients to comment on their participation in an N-of-1 trial
      and this research process. Followup of patients 3 months after completion of their N-of-1
      trial will include determining current medication and a current outcome assessment.
      Investigators will record all adverse drug reactions and patients withdrawn from studies.
      They will also record the reason for withdrawal for all patients choosing to withdraw. We
      will include results from patients who drop out due to reasons other than drug reactions in
      the combined N-of-1 analyses if completed period pair results are available. An independent
      safety officer will review all withdrawals.

      Results of individual patient trials will be confidential; however, we will combine these
      results (after removal of patient identifiers) with the results of other patients, and will
      publish the overall results of this study. We will maintain the connection of results to
      patient identifiers only to enable us to provide results to individual investigators and
      their patients.
    

Intervention name(s): Amitriptyline; Amitriptyline plus Fluoxitine
Intervention type(s): Drug; Drug
Intervention description(s): Amitriptyline 25 mg po; Amitriptyline 25 mg po plus Fluoxitine 20 mg po
Other intervention name(s): Elavil; elavil plus prozac
Intervention MeSH terms: Amitriptyline
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Fibromyalgia Syndrome (FMS); Amitriptyline; Fluoxetine