Combining N-of-1 Trials to Assess Fibromyalgia Treatments

Study Overview
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Brief Summary
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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
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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.

Official Title
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Combining N-of-1 Trials to Assess Fibromyalgia Therapies

Conditions
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Fibromyalgia

Intervention / Treatment
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* Drug: Amitriptyline
* Drug: Amitriptyline plus Fluoxitine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Patients received each intervention multiple times in random-order crossover design. | Drug: Amitriptyline<br>* Amitriptyline 25 mg po<br>* Other names: Elavil;Drug: Amitriptyline plus Fluoxitine<br>* Amitriptyline 25 mg po plus Fluoxitine 20 mg po<br>* Other names: elavil plus prozac;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FIbromyalgia Impact Questionnaire scores |  | At baseline,each treatment period, and at 3 mo follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fibromyalgia Syndrome (FMS), Amitriptyline, Fluoxetine