FibromyalgiaPhase 4NCT00000428
Combining N-of-1 Trials to Assess Fibromyalgia Treatments
A Phase 4 study testing Amitriptyline and Amitriptyline plus Fluoxitine in people with Fibromyalgia, run by Tufts Medical Center at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Fibromyalgia
- What is being tested?
- Amitriptyline and Amitriptyline plus Fluoxitine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 7 sitesUnited States
- Study dates
- Sep 2000to Mar 2004
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Office of Raphael Kieval, MD
Brockton, Massachusetts, 02402
Office of Ronald J. Rapoport, MD
Fall River, Massachusetts, 02720
Office of Eileen Winston, MD
Framingham, Massachusetts, 01702
Office of Nicola Mogavero, MD
Melrose, Massachusetts, 02176
Office of Jacqueline Feuer, MD
Needham, Massachusetts, 02192
Newton-Wellesley Hospital
Newton, Massachusetts, 02162
Office of Sharon A. Stotsky, MD
North Reading, Massachusetts, 01864
About this study
Official title: Combining N-of-1 Trials to Assess Fibromyalgia Therapies
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.
Read the 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.
- Conditions
- Fibromyalgia
- Being tested
- Amitriptyline, Amitriptyline plus Fluoxitine
- Keywords
- Fibromyalgia Syndrome (FMS), Amitriptyline, Fluoxetine
- Medical subject headings
- Fibromyalgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmitriptylineDrug
Also called Elavil
Amitriptyline 25 mg po
Amitriptyline plus FluoxitineDrug
Also called elavil plus prozac
Amitriptyline 25 mg po plus Fluoxitine 20 mg po
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Patients received each intervention multiple times in random-order crossover design. Receives: Drug: Amitriptyline; Drug: Amitriptyline plus Fluoxitine |
What is being measured
The primary outcome is the main question the study is designed to answer.
FIbromyalgia Impact Questionnaire scores
Measured: At baseline,each treatment period, and at 3 mo follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2000 (estimated)
- Study startSep 2000
- Primary completionMar 2004
- Study completionMar 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for FibromyalgiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tufts Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Investigators
- Deborah R. Zucker, Principal investigator, New England Medical Center, Tufts University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000428
- Sponsor's protocol ID
- R01AR045416
- Other IDs
- R01AR045416, NIAMS-038
- Status last verified
- Jul 2013
- First submitted
- 18 Jan 2000
- Last updated
- 1 Aug 2013
- Results posted
- No
- Data monitoring committee
- Yes
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. doi: 10.1002/art.1780391111.
PubMed 8912507Zucker 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. doi: 10.1016/s0895-4356(96)00429-5.
PubMed 9179098Guyatt 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. doi: 10.1056/NEJM198604033141406.
PubMed 2936958Guyatt 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.
PubMed 3409138Larson EB. N-of-1 clinical trials. A technique for improving medical therapeutics. West J Med. 1990 Jan;152(1):52-6.
PubMed 2309473Zucker DR, Ruthazer R, Schmid CH, Feuer JM, Fischer PA, Kieval RI, Mogavero N, Rapoport RJ, Selker HP, Stotsky SA, Winston E, Goldenberg DL. Lessons learned combining N-of-1 trials to assess fibromyalgia therapies. J Rheumatol. 2006 Oct;33(10):2069-77.
PubMed 17014022
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combining N-of-1 Trials to Assess Fibromyalgia Therapies
- ClinicalTrials.gov ID
- NCT00000428
- Acronym / sponsor ID
- R01AR045416
- Conditions
- Fibromyalgia
- Keywords
- Fibromyalgia Syndrome (FMS), Amitriptyline, Fluoxetine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Tufts Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- Sep 2000
- Primary completion
- Mar 2004 (actual)
- Study completion
- Mar 2004 (actual)
- First posted
- 19 Jan 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Amitriptyline, Drug: Amitriptyline plus FluoxitinePatients received each intervention multiple times in random-order crossover design. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmitriptylineAlso: ElavilAmitriptyline 25 mg po | Drug | 1 |
| Amitriptyline plus FluoxitineAlso: elavil plus prozacAmitriptyline 25 mg po plus Fluoxitine 20 mg po | Drug | 1 |
Primary outcome
FIbromyalgia Impact Questionnaire scores
Time frame: At baseline,each treatment period, and at 3 mo follow up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2013.
- Background: PubMed 8912507Goldenberg 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. doi: 10.1002/art.1780391111.
- Background: PubMed 9179098Zucker 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. doi: 10.1016/s0895-4356(96)00429-5.
- Background: PubMed 2936958Guyatt 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. doi: 10.1056/NEJM198604033141406.
- Background: PubMed 3409138Guyatt 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.
- Background: PubMed 2309473Larson EB. N-of-1 clinical trials. A technique for improving medical therapeutics. West J Med. 1990 Jan;152(1):52-6.
- Results publication: PubMed 17014022Zucker DR, Ruthazer R, Schmid CH, Feuer JM, Fischer PA, Kieval RI, Mogavero N, Rapoport RJ, Selker HP, Stotsky SA, Winston E, Goldenberg DL. Lessons learned combining N-of-1 trials to assess fibromyalgia therapies. J Rheumatol. 2006 Oct;33(10):2069-77.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deborah R. Zucker principal investigator
New England Medical Center, Tufts University School of Medicine
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Amitriptyline and Amitriptyline plus Fluoxitine in people with Fibromyalgia, run by Tufts Medical Center at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FIbromyalgia Impact Questionnaire scores (time frame: At baseline,each treatment period, and at 3 mo follow up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000428, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2013.