Drug and Talk Therapy for Fibromyalgia

Study Overview
=================
Brief Summary
-----------------
Fibromyalgia Syndrome (FMS) afflicts 2% of the U.S. population and have huge individual and societal costs in terms of quality of life, social and work functioning, health care use, and lost productivity. Although single therapy approaches such as medication, graduated exercise, and Cognitive Behavioral Therapy (CBT) are well-established treatment approaches, the majority of FMS continue to report significant levels of pain and pain-related disability. Testing the efficacy of using combination therapies such and CBT with medication has considerable potential to maximize treatment response. Also, exploring the biological and psychological mechanisms underlying combination treatment may pave the way for developing new treatments for FMS sufferers. We chose to study drug and CBT for several reasons: 1) the scarcity of trials that manipulate medications along with CBT in FMS, 2) the prohibitive nature of adding an exercise treatment arm in a study that has both time and budgetary constraints, 3) the complexity in understanding the mechanism of actions of 3 different modes of intervention in one clinical trial, and 4) the desire to explore mechanisms in this program of research, in particular the potential effects of a biological intervention (drug) on what is traditionally considered a psychological outcome (pain-related attributions and cognition) and the potential effects of a psychological intervention (CBT) on what is traditionally considered a physiological outcome (pain sensitivity).

Detailed Description
-----------------
Qualified participants will take part in a 21-week clinical research study entitled, Drug and Talk Therapy for Fibromyalgia. We are doing this study to better understand how talk therapies, such as education and cognitive behavioral therapy (CBT), can improve the therapeutic benefits of drug for fibromyalgia. Savella ®, (milnacipran) is an FDA approved drug for fibromyalgia. The safety and efficacy of Savella has been established in two US-based clinical studies involving over 2,000 patients with fibromyalgia. Because Savella has already been shown to be effective when used in isolation to treat fibromyalgia, we are conducting the study to determine whether combination treatment (Savella + talk therapy) is more efficacious than just Savella alone or talk therapy alone. Volunteers will be randomized (like flipping a coin) on two different levels: Each participate will be randomized into one of two groups for medication: One group will receive Savella and the other group will receive a placebo (no medicinal value). Both the medication and the placebo will look identical and subjects will not be told into which group they have been placed until the completion of the study. Each participants has 66% chance of receiving Savella and 34% chance of getting the placebo. The second level of randomization will be to determine which type of talk therapies you will be assigned to. Subjects will be randomly assigned to receive educational instruction relevant to fibromyalgia, OR cognitive behavioral therapy which includes a workbook. Both talk therapies will be provided over the phone once a week for 8 weeks. Each phone session may last for 30 minutes. Importantly, both talk therapies can provide coping tools and information designed to help manage fibromyalgia symptoms. Study Overview: Subjects will be asked to visit the Fibromyalgia Clinical Research Center on five separate occasions: Initial Screening (today's visit), Week 1, Week 2, Week 9, and Week 21. VISIT 1: Informed consent and initial screening questionnaire,physical assessment Issue a 'pain score' wrist monitor with instructions to record current pain level three times a day for one week VISIT 2: Submit your pain recording Complete the self-assessment questionnaires via computer Vital signs check Undergo pain sensitivity testing If qualified, subjects be randomized to receive Savella or placebo AND to receive education or cognitive behavioral therapy VISIT 3: We will assess the subject's willingness to continue participation. Review medication diary and medication side-effect checklist. Schedule PHONE Therapy sessions: 8 thirty minute calls VISIT 4: One week prior to this visit, subjects will receive a 'pain score' monitor in order to enter current pain levels three times a day for one week. Then report for this visit. Review side effect checklist, medication diary. Completion of self-assessment questionnaires via computer Undergo pain sensitivity testing VISIT 5: One week prior to this visit, subjects will receive a 'pain score' monitor in order to enter current pain levels three times a day for one week. Then report for this visit. Review side effect checklist, medication diary. Completion of self-assessment questionnaires via computer Undergo pain sensitivity testing Upon visit completion, participants will receive a reduced dose regimen of the medication along with written and verbal instructions to safely discontinue the study medication.

Official Title
-----------------
A Pilot Study on the Combined Use of Cognitive Behavioral Therapy (CBT) and Milnacipran

Conditions
-----------------
Fibromyalgia

Intervention / Treatment
-----------------
* Other: CBT and milnacipran
* Behavioral: CBT with a placebo
* Drug: Educational with milnacipran


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must be between the ages of 18 to 65 years of age Must have been diagnosed with fibromyalgia by a rheumatologist Must have an overall body pain average score ≥ 4 Must be on stable doses of your current medication for at least past four weeks Must report all medication including herbal supplements and over-the-counter medications that you are currently taking to a member of the research team. Must limit any changes in your medication(s)during the 21-week study time period unless medically necessary Must be willing to maintain a medication diary provided to you during the 21-week study period Must be willing to abstain (not take) any fibromyalgia related medication (including over-the-counter)for at least 6-hours prior to each of the three testing visits. (Otherwise, you may take these medication immediately after pain sensitivity testing has been completed and as prescribed in-between visits) Must experience the symptoms of fibromyalgia syndrome (FMS) that decreases (limits) your ability to perform daily activities. Exclusions Criteria: You have uncontrolled hypertension(high blood pressure) systolic >160 mm Hg or diastolic blood pressure > 100 mm Hg) If you have a history of: heart disease, glaucoma, or hepatitis You have been diagnosed with any type of peripheral neuropathy You have a body mass index (BMI) of more than 34 You currently or frequently have thoughts of harming yourself or committing suicide. You are in the process of filing, or plan to file for disability benefits within the study timeline. You plan to undergo an elective surgery within the study timeline. You have been diagnosed with another major rheumatic conditions (i.e. rheumatoid arthritis, systemic lupus erythematosus, scleroderma and other connective tissue diseases) You are currently pregnant, are planning to become pregnant, or are breastfeeding You have been diagnosed with schizophrenia or manic-depressive. You are currently taking any of the following medications: fluoxetine, Brand Names: Prozac, Prozac Weekly, Rapiflux, Sarafem sertraline, Brand Name: Zoloft paroxetine, Brand Names: Paxil, Paxil CR, Pexeva citalopram, Brand Name: Celexa escitalopram, Brand Names: Lexapro venlafaxine, Brand Names: Effexor, Effexor XR mirtazapine, Brand Names: Remeron, Remeron SolTab duloxetine, Brand Name: Cymbalta NOTE: If you are taking any of the medication(s) listed above and are willing to discontinue its use for the duration of this study, you must first discuss your decision with your primary care physician (or prescribing doctor)regarding the appropriate regimen to wean off your current medication and receive his/her written consent before proceeding with enrollment. We will provide you a Dear Doctor letter that explains the study details. If you are currently taking or have ever taken Savella® (milnacipran) You are currently participating in other pain research study or have previously been enrolled in any study or class in which cognitive behavioral therapy or educational formats were used to help control pain or stress related to fibromyalgia You are unwilling or unable to comply with the study guidelines Note: If you have ever experienced an adverse event while taking any type of antidepressant, please alert the research team, while it may not exclude you from participating in the study, it is important that we are aware of the incident in order to keep you safe.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBT and milnacipran<br>Subjects randomized to this group will receive a combination of eight telephone sessions of Cognitive Behavior Therapy (CBT) and a 21-week regimen of milnacipran. | Other: CBT and milnacipran<br>* Participants will receive a series of eight telephone sessions of CBT along with a 21-week regimen of milnacipran. Dosing for milnacipran begins with a one week starter pack. Dosage:12.5 mg on day 1,12.5 mg twice daily on days 2 and 3, then 25 mg twice daily on days 4,5,6,and 7. On day 8 participants will begin taking 50 mg twice daily for the balance of the study.<br>* Other names: fibromyalgia;|
| Placebo Comparator: CBT and placebo<br>Subjects randomized to this arm will receive a series of eight telephone sessions of Cognitive Behavioral Therapy (CBT) along with a 21-week regimen of a placebo(sugar pill)medication. | Behavioral: CBT with a placebo<br>* Participants will receive a series of eight telephone sessions of CBT along with a 21-week regimen of a placebo. Dosing for the placebo begins with a one week starter pack. Dosage: 12.5 mg on day 1,12.5 mg twice daily on days 2 and 3, then 25 mg twice daily on days 4,5,6,and 7. On day 8 participants will begin taking 50 mg twice daily for the balance of the study.<br>* Other names: fibromyalgia;|
| Active Comparator: Educational with milnacipran<br>Subjects randomized to this group will receive a series of eight educational phone calls regarding fibromyalgia along with a 21-week regimen of milnacipran. | Drug: Educational with milnacipran<br>* Participants will receive a series of eight telephone sessions of fibromyalgia related education along with a 21-week regimen of milnacipran. Dosing for milnacipran begins with a one week starter pack. Dosage:12.5 mg on day 1,12.5 mg twice daily on days 2 and 3, then 25 mg twice daily on days 4,5,6,and 7. On day 8 participants will begin taking 50 mg twice daily for the balance of the study.<br>* Other names: Savella;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Weekly Average Pain Intensity | Change in weekly average pain intensity score from baseline to week 21 (scale from -10 to +10; the more negative the value, the better in terms of pain reduction) | Baseline and Week 21clinic visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Evoked Pain Scores | 0 to 20 pain scale, with higher pain score representing greater sensitivity to pressure pain stimuli | Baseline and Week 21 clinic visits | 
| Identification of Group Assignment | Subjects identifying group assignment correctly | week 21 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
FMS, Fibromyalgia