A Pilot Study of TMS Effects on Pain and Depression in Patients With Fibromyalgia

Study Overview
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Brief Summary
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In this pilot study, the PI proposes to include 20 African American participants with Fibromyalgia to explore the effect of r TMS on pain and depressive symptoms.

Detailed Description
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In this pilot study, the PI proposes to include 20 African American participants with Fibromyalgia to explore the effect of r TMS on pain and depressive symptoms. The focus on African Americans is due to the mandate from the funding source (internal), as well as possible higher prevalence of FM in AA women. If recruitment is slow, the PI proposes to open up the study to other groups. Twenty subjects will be randomized to either sham or active TMS condition. Inclusion/exclusion criteria are well thought out and seem appropriate. mTreatments will be administered at IOP 5 times/wk with each session lasting 20 minutes. Pain intensity and unpleasantness will be measured pre and post each TMS session using three different pain evaluation paradigms. GCRC resource is mainly requested for two blood draws pre and post first TMS session. The blood samples will be used to measure inflammatory cytokines IL-1, IL-6, AND IL-8. The main aim is to ascertain feasibility of the study and secondary aim is to gather information on variability in response for power analysis for future larger study. The introduction and rationale (including pain evaluation, and methods relating to TMS) are clearly presented. Use of GCRC resources seem appropriate.

Official Title
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A Pilot Study of Transcranial Magnetic Stimulation (TMS) Effects on Pain and Depression in Patients With Fibromyalgia

Conditions
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Major Depression, Fibromyalgia

Intervention / Treatment
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* Device: Active TMS
* Device: Sham TMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-80, meet ACR criteria for FM for more than 6 months, may or may not have a diagnosis of major depressive disorder (not bipolar) past or present, Current major depressive episode must be without psychotic features Not be on medication known to increase risk of TMS-induced seizures No prescription medication changes in the previous 4 weeks with agreement not to change during the treatment course (2 weeks) and 2 weeks thereafter No history of epilepsy or stroke or recent head trauma (LOC > 5 minutes) within the past 6 months African Americans will be initially sought out for study, however the recruitment may extend to include Caucasian and Hispanic subjects to carry out the study. Exclusion Criteria: Primary, current diagnosis of schizophrenia Other (non-mood disorder) psychosis Mental retardation Substance dependence or abuse within the past 6 months (except nicotine) Psychotic features in this episode, dementia, or delirium Contraindication to rTMS Increased intracranial pressure Brain surgery, or head trauma with loss of consciousness for > 15 minutes Implanted electronic device Metal in the head, or pregnant Has an active autoimmune, endocrine, viral, or vascular disorder affecting the brain or unstable cardiac disease Uncontrolled hypertension, or severe renal or liver insufficiency Unstable and active suicidal intent or plan History of attempt requiring medical hospitalization within in the past 6 months -currently an involuntary inpatient on a psychiatric ward.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active TMS<br>Since cortical stimulation can be performed non-invasively by active Transcranial Magnetic Stimulation (TMS), Participants in the active TMS group, receive five 20 minute active TMS treatment sessions per week for two weeks. | Device: Active TMS<br>* Active TMS uses the active TMS coil to stimulate the cortical area of interest. Active TMS involves 80 trains x 15 sec = 4000 pulses per session, 5 x per week= 20,000 pulses per week, x 2 weeks = 40,000 pulses.<br>* Other names: Neotonus model 2100 xxx;|
| Sham Comparator: Sham TMS<br>To prevent unwanted cortical activation, Sham TMS will be employed in the Sham TMS group. For the Sham TMS group, a specially designed sham TMS coil will be used for all sham conditions. This sham TMS coil produces auditory signals identical to active TMS coils but is shielded so that actual stimulation does not occur. This approach is currently the state-of-the-art approach to sham TMS procedures and is employed in high-quality clinical TMS trials. Participants in the sham TMS group receive five 20 minute Sham TMS treatment sessions per week for two weeks. | Device: Sham TMS<br>* Sham TMS uses the same stimulation frequency as the Active TMS but uses the Sham TMS coil instead to prevent actual stimulation from occurring (chosen as a priori stimulation based on studies showing antidepressant and anti-nociceptive effects): 10 Hertz - Pulse train duration (on time) 5 seconds, Power (intensity) level 120% of stored motor threshold, Inter-train interval (off time) 10 seconds (15 second cycle time). Additionally, stimulation-train duration and inter-stimulus intervals were determined such that they are in compliance with current published rTMS safety guidelines.<br>* Other names: Neotonus model 2100 xxx;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Pain | To assess each participant's average Pain in the past 24 hours, The Brief Pain Inventory (BPI)-short form will be administered. The BPI rapidly assesses the severity of pain and its impact on functioning and has been widely used in both research and clinical settings. Participants rate their average pain in the past 24 hours using a 0-10 numerical rating scale, where 0=no pain and 10=extreme pain. | Baseline, After Week 1 of Treatment, After Week 2 of Treatment, One week Post Treatment follow up, and Two week post treatment follow up | 
| THE FIBROMYALGIA IMPACT QUESTIONNAIRE (FIQ)-Modified | To assess the impact of fibromyalgia on each participant's function, the FIQ-modified (2002) version will be administered before each study visit. The FIQ-modified (2002) version assesses the following symptoms; physical Impairment, well-being, pain, fatigue, rested, stiffness, anxiety, and depression within the past 24 hours. Each symptom scale ranges from 0 to 10. For example, 0=no pain and 10=extreme pain, 0=not fatigued and 10=extremely fatigued. The final score is the total score which ranges from 0 to 80. Higher scores indicate greater impact of fibromyalgia on functioning. | Baseline, After Week 1 of Treatment, After Week 2 of Treatment, One week Post Treatment follow up, and Two week post treatment follow up | 
| THE HAMILTON DEPRESSION RATING SCALE (HRDS) | To assess each participant's level of depression, the HRDS will be administered. The HRDS is a 17-item clinician-rated scale that is designed to evaluate depressed mood, vegetative and cognitive symptoms of depression, and comorbid anxiety symptoms. Eight items are scored on a 5-point scale, ranging from 0-4, where 0=not present and 4=severe. Nine items are scored from 0-2, where 0=None, 1=Mild, and 2=Severe. The final, total score ranges from 0-52. Scores in the range of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression, and scores over 24 are indicative of severe depression. | Baseline, After Week 1 of Treatment, After Week 2 of Treatment, One week Post Treatment follow up, and Two week post treatment follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depression, Fibromyalgia, TMS