Combining N-of-1 Trials to Assess Fibromyalgia Treatments

Condition(s) targeted: Fibromyalgia

Intervention: Amitriptyline (Drug); Amitriptyline plus Fluoxitine (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Official(s) and/or principal investigator(s):
Deborah R. Zucker, Principal Investigator, Affiliation: New England Medical Center/ Tufts University School of Medicine

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.

Official title: Combining N-of-1 Trials to Assess Fibromyalgia Therapies

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Crossover Assignment, Efficacy Study

Primary outcome: FIbromyalgia Impact Questionnaire scores

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.

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.

Criteria:

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

Newton-Wellesley Hospital, Newton, Massachusetts 02162, United States

Office of Jacqueline Feuer, MD, Needham, Massachusetts 02192, United States

Office of Raphael Kieval, MD, Brockton, Massachusetts 02402, United States

Office of Nicola Mogavero, MD, Melrose, Massachusetts 02176, United States

Office of Ronald J. Rapoport, MD, Fall River, Massachusetts 02720, United States

Office of Sharon A. Stotsky, MD, North Reading, Massachusetts 01864, United States

Office of Eileen Winston, MD, Framingham, Massachusetts 01702, United States

Related publications:

Goldenberg D, Mayskiy M, Mossey C, Ruthazer R, Schmid C. A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia. Arthritis Rheum. 1996 Nov;39(11):1852-9.

Zucker DR, Schmid CH, McIntosh MW, D'Agostino RB, Selker HP, Lau J. Combining single patient (N-of-1) trials to estimate population treatment effects and to evaluate individual patient responses to treatment. J Clin Epidemiol. 1997 Apr;50(4):401-10.

Guyatt G, Sackett D, Taylor DW, Chong J, Roberts R, Pugsley S. Determining optimal therapy--randomized trials in individual patients. N Engl J Med. 1986 Apr 3;314(14):889-92.

Guyatt G, Sackett D, Adachi J, Roberts R, Chong J, Rosenbloom D, Keller J. A clinician's guide for conducting randomized trials in individual patients. CMAJ. 1988 Sep 15;139(6):497-503.

Larson EB. N-of-1 clinical trials. A technique for improving medical therapeutics. West J Med. 1990 Jan;152(1):52-6. No abstract available.

Starting date: September 2000
Ending date: March 2004
Last updated: March 5, 2008