Fibromyalgia, Major Depression
Conditions
Keywords
Major Depression, Fibromyalgia, TMS
Brief summary
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
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.
Interventions
DEVICEActive TMS
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.
DEVICESham TMS
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.
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average 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 | 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. |
| THE FIBROMYALGIA IMPACT QUESTIONNAIRE (FIQ)-Modified | Baseline, After Week 1 of Treatment, After Week 2 of Treatment, One week Post Treatment follow up, and Two week post treatment follow up | 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. |
| THE HAMILTON DEPRESSION RATING SCALE (HRDS) | Baseline, After Week 1 of Treatment, After Week 2 of Treatment, One week Post Treatment follow up, and Two week post treatment follow up | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active TMS Participants receive 5 Active TMS treatment sessions per week for two weeks. Active stimulation 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. Time - 1200 sec = 20 minutes/ session, all days.
Active TMS: 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. Time - 1200 sec = 20 minutes/ session, all days. | 10 |
| Sham TMS Participants receive 5 Sham TMS treatment sessions per week for two weeks. Sham stimulation 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. Time - 1200 sec = 20 minutes/ session, all days.
Sham TMS: Sham TMS will use the same stimulation frequency for all active subjects (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. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Sham TMS | Total | Active TMS |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 20 Participants | 10 Participants |
| Age, Continuous | 51.67 years STANDARD_DEVIATION 18.19 | 53 years STANDARD_DEVIATION 13.53 | 54.20 years STANDARD_DEVIATION 8.28 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 20 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 10 Participants | 20 Participants | 10 Participants |
| Sex: Female, Male Female | 8 Participants | 17 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
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.
Time frame: Baseline, After Week 1 of Treatment, After Week 2 of Treatment, One week Post Treatment follow up, and Two week post treatment follow up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active TMS | Average Pain | After Week 1 of Treatment | 4.90 units on a scale | Standard Deviation 1.89 |
| Active TMS | Average Pain | 1 week post treatment follow up | 4.19 units on a scale | Standard Deviation 1.9 |
| Active TMS | Average Pain | After Week 2 of Treatment | 3.99 units on a scale | Standard Deviation 1.9 |
| Active TMS | Average Pain | 2 week post treatment follow up | 4.41 units on a scale | Standard Deviation 1.95 |
| Active TMS | Average Pain | Baseline | 5.60 units on a scale | Standard Deviation 1.85 |
| Sham TMS | Average Pain | 2 week post treatment follow up | 5.37 units on a scale | Standard Deviation 2.02 |
| Sham TMS | Average Pain | Baseline | 5.43 units on a scale | Standard Deviation 1.82 |
| Sham TMS | Average Pain | After Week 1 of Treatment | 5.49 units on a scale | Standard Deviation 1.9 |
| Sham TMS | Average Pain | After Week 2 of Treatment | 5.07 units on a scale | Standard Deviation 1.89 |
| Sham TMS | Average Pain | 1 week post treatment follow up | 4.76 units on a scale | Standard Deviation 1.9 |
Primary
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.
Time frame: Baseline, After Week 1 of Treatment, After Week 2 of Treatment, One week Post Treatment follow up, and Two week post treatment follow up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active TMS | THE FIBROMYALGIA IMPACT QUESTIONNAIRE (FIQ)-Modified | 1 week Post Treatment follow up | 49.29 units on a scale | Standard Deviation 19.27 |
| Active TMS | THE FIBROMYALGIA IMPACT QUESTIONNAIRE (FIQ)-Modified | Baseline | 58.79 units on a scale | Standard Deviation 11.93 |
| Active TMS | THE FIBROMYALGIA IMPACT QUESTIONNAIRE (FIQ)-Modified | After Week 1 of Treatment | 55.03 units on a scale | Standard Deviation 16.93 |
| Active TMS | THE FIBROMYALGIA IMPACT QUESTIONNAIRE (FIQ)-Modified | After Week 2 of Treatment | 42.07 units on a scale | Standard Deviation 18.13 |
| Active TMS | THE FIBROMYALGIA IMPACT QUESTIONNAIRE (FIQ)-Modified | 2 week Post Treatment follow up | 38.99 units on a scale | Standard Deviation 19.44 |
| Sham TMS | THE FIBROMYALGIA IMPACT QUESTIONNAIRE (FIQ)-Modified | After Week 2 of Treatment | 51.50 units on a scale | Standard Deviation 17.32 |
| Sham TMS | THE FIBROMYALGIA IMPACT QUESTIONNAIRE (FIQ)-Modified | 1 week Post Treatment follow up | 43.47 units on a scale | Standard Deviation 16.1 |
| Sham TMS | THE FIBROMYALGIA IMPACT QUESTIONNAIRE (FIQ)-Modified | 2 week Post Treatment follow up | 47.93 units on a scale | Standard Deviation 14.7 |
| Sham TMS | THE FIBROMYALGIA IMPACT QUESTIONNAIRE (FIQ)-Modified | After Week 1 of Treatment | 51.22 units on a scale | Standard Deviation 15.96 |
| Sham TMS | THE FIBROMYALGIA IMPACT QUESTIONNAIRE (FIQ)-Modified | Baseline | 54.38 units on a scale | Standard Deviation 13.96 |
Primary
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.
Time frame: Baseline, After Week 1 of Treatment, After Week 2 of Treatment, One week Post Treatment follow up, and Two week post treatment follow up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active TMS | THE HAMILTON DEPRESSION RATING SCALE (HRDS) | Baseline | 21.80 units on a scale | Standard Deviation 7.79 |
| Active TMS | THE HAMILTON DEPRESSION RATING SCALE (HRDS) | After Week 1 of Treatment | 17.30 units on a scale | Standard Deviation 8.27 |
| Active TMS | THE HAMILTON DEPRESSION RATING SCALE (HRDS) | 1 week post treatment follow up | 15.80 units on a scale | Standard Deviation 8.74 |
| Active TMS | THE HAMILTON DEPRESSION RATING SCALE (HRDS) | After Week 2 of Treatment | 16.10 units on a scale | Standard Deviation 8.19 |
| Active TMS | THE HAMILTON DEPRESSION RATING SCALE (HRDS) | 2 week post treatment follow up | 14.10 units on a scale | Standard Deviation 9.42 |
| Sham TMS | THE HAMILTON DEPRESSION RATING SCALE (HRDS) | 1 week post treatment follow up | 17.20 units on a scale | Standard Deviation 7.55 |
| Sham TMS | THE HAMILTON DEPRESSION RATING SCALE (HRDS) | Baseline | 17.60 units on a scale | Standard Deviation 7.31 |
| Sham TMS | THE HAMILTON DEPRESSION RATING SCALE (HRDS) | 2 week post treatment follow up | 16.40 units on a scale | Standard Deviation 8.18 |
| Sham TMS | THE HAMILTON DEPRESSION RATING SCALE (HRDS) | After Week 1 of Treatment | 17.40 units on a scale | Standard Deviation 8.42 |
| Sham TMS | THE HAMILTON DEPRESSION RATING SCALE (HRDS) | After Week 2 of Treatment | 15.30 units on a scale | Standard Deviation 7.62 |