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Combining N-of-1 Trials to Assess Fibromyalgia Treatments

Phase 4
Completed
Conditions
Fibromyalgia
Interventions
Registration Number
NCT00000428
Lead Sponsor
Tufts Medical Center
Brief 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
58
Inclusion Criteria
  • Patients who meet fibromyalgia criteria as defined by the American College of Rheumatology
  • No systemic illness (current or past) or other contraindications to taking study medications (e.g. known hypersensitivity)
  • Age 18-60
  • Patient willingness, and physician agreement, to discontinue CNS medications/NSAIDs/analgesics for 1 week prior to starting their trial
  • Patient informed consent and agreement to participate in an N-of-1 trial
Exclusion Criteria
  • Patients who are currently pregnant or who plan to become pregnant during the study period
  • Patients with any contraindications to using either amitriptyline or fluoxetine

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
1Amitriptyline plus FluoxitinePatients received each intervention multiple times in random-order crossover design.
1AmitriptylinePatients received each intervention multiple times in random-order crossover design.
Primary Outcome Measures
NameTimeMethod
FIbromyalgia Impact Questionnaire scoresAt baseline,each treatment period, and at 3 mo follow up
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (7)

Office of Raphael Kieval, MD

🇺🇸

Brockton, Massachusetts, United States

Office of Eileen Winston, MD

🇺🇸

Framingham, Massachusetts, United States

Newton-Wellesley Hospital

🇺🇸

Newton, Massachusetts, United States

Office of Ronald J. Rapoport, MD

🇺🇸

Fall River, Massachusetts, United States

Office of Sharon A. Stotsky, MD

🇺🇸

North Reading, Massachusetts, United States

Office of Nicola Mogavero, MD

🇺🇸

Melrose, Massachusetts, United States

Office of Jacqueline Feuer, MD

🇺🇸

Needham, Massachusetts, United States

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