Fibromyalgia
Conditions
Keywords
Fibromyalgia, neuronavigated-rTMS, pain, stiffness, fatigue
Brief summary
This study aims to evaluate the effectiveness of 10 Hz neuronavigated repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (DLPFC) on pain, stiffness, fatigue, depression/anxiety, quality of life and cognitive functions in fibromyalgia syndrome (FMS).
Detailed description
This is a single-center, prospective, randomized, double-blind, sham-controlled study in two-arm parallel-group design. Twenty participants will be randomized into 2 groups. Randomization will be performed using computer-generated block randomization with 1:1 allocation between the active rTMS group (Group 1) and the sham-control group (Group 2). Group 1 will receive high frequency repetitive transcranial magnetic stimulation (10hz-HF-rTMS)-A total 14 sessions of HF-rTMS, 10 sessions daily (5 days/week, 2 weeks) and 4 sessions weekly (1 day/week, 4 weeks). Group 2 will receive sham stimulation-A total 14 sessions of sham-rTMS, 10 sessions daily (5 days/week, 2 weeks) and 4 sessions weekly (1 day/week, 4 weeks).All patients will be evaluated with pain severity (VAS-10mm),stiffness severity (VAS-10mm), Fibromyalgia Impact Questionnaire (FIQ), Fatigue Severity Scale (FSS), Hospital Depression Anxiety Scale (HADS), Addenbrook Cognitive Examination-revised version (ACE-R).Patients will be questioned for the safety of treatment. Available drug therapies will be continued in both groups. Patients and clinical raters will be blinded to treatment. All patients will be reviewed by the investigator in terms of rTMS treatment safety and motor threshold determination before each treatment session and observed for possible side effects after treatment. All side effects will be recorded. Magnetic stimulation will be applied using Neurosoft-Neuro MS/D with a figure-of-eight-shaped coil. rTMS therapy will be applied under the guide of neuronavigation with the following parameters: target-left DLPFC, with the %90 of the RMT, 10 Hz stimulation for 5 seconds intervals (on) with 25 seconds inter-train intervals (off), 15 minutes, 1500 pulses.
Interventions
DEVICErTMS + Neuronavigation
Repetitive Transcranial Magnetic Stimulation (Neuro-MS/D) + Neural Navigator
Sponsors
Izmir Katip Celebi University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adults (age between 18-65 years) * Diagnosis of fibromyalgia syndrome according to 2016 Fibromyalgia diagnostic criteria * The mean pain intensity is VAS ≥ 4/10 * Stable treatment for at least last 3 months * Patients accepting participation by signing an informed consent form
Exclusion criteria
* To have a clinical condition to be contraindicated for TMS (metallic implant, cardiac pace, pregnancy, lactation, epilepsy, head trauma, history of cranial operation...) * The presence of malignancy * Systemic rheumatic diseases * Major orthopedic / neurological problems that limit daily life activities * Alcohol or drug addiction * Major depression / personality disorder history * Have received TMS treatment before * Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analog Scale-Pain | in the second week | The severity of the pain at rest was assessed on a 10 cm visual analog scale (Total score: 0-10)(0=no pain, 10=severe pain) Higher scores mean a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analog Scale-Pain | in the sixth week | The severity of the pain at rest was assessed on a 10 cm visual analog scale (Total score: 0-10)(0=no pain, 10=severe pain) Higher scores mean a worse outcome. |
| Fibromyalgia Impact Questionnaire | in the sixth week | Functional health status and quality of life of the participants were assessed with the Fibromyalgia impact questionnaire, which measures 10 different features (physical functioning, missed days of work, depression, anxiety, feeling good, morning tiredness, pain, stiffness, fatigue, and well-being over the past week). The total Fibromyalgia impact questionnaire score is maximum 80 points. Higher scores indicate lower functionality level. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Hospital Anxiety and Depression Scale | in the sixth week | Hospital anxiety and depression scale is an assessment tool developed to identify the risk of anxiety and depression and measure its level and change of severity. Its subscales are anxiety and depression. It contains 14 questions in total, including 7 (odd numbers) measuring anxiety and 7 (even numbers) measuring depression. The lowest and highest total score that a person can obtain from this scale are 0 and 42, respectively. High scores are associated with a worse psychiatric condition. |
| Visual Analog Scale-Stiffness | in the second week | The severity of the stiffness at rest was assessed on a 10 cm visual analog scale (Total score: 0-10)(0=no stiffness, 10=severe stiffness) Higher scores mean a worse outcome. |
| Addenbrook Cognitive Examination Revised | in the sixth week | Addenbrook Cognitive Examination-Revised is a brief cognitive test that consists of 5 basic sections: attention and orientation, memory, verbal fluency, language and visual-spatial abilities. Total score that can be obtained is 0-100. Higher scores are associated with a better cognitive state. |
| Fibromyalgia Impact Questionnaire | in the second week | Functional health status and quality of life of the participants were assessed with the Fibromyalgia impact questionnaire, which measures 10 different features (physical functioning, missed days of work, depression, anxiety, feeling good, morning tiredness, pain, stiffness, fatigue, and well-being over the past week). The total Fibromyalgia impact questionnaire score is maximum 80 points. Higher scores indicate lower functionality level. |
| Fatigue Severity Scale | in the sixth week | Severity of fatigue was evaluated with Fatigue severity scale, a 9-item self-report questionnaire scale. Each item of this scale consists of statements that are scored on a seven-point Likert type scale ranging from 1 to 7. Total Fatigue severity scale score is calculated as the mean value of nine items. Higher scores indicate higher fatigue severity. (Total score range: 1-7) |
Countries
Turkey (Türkiye)
Participant flow
Recruitment details
Participants were recruited from Physical Medicine and Rehabilitation (PMR) outpatient clinics of a university hospital.
Pre-assignment details
Twenty-eight patients were evaluated for participation in the study. Eight patients were excluded.
Participants by arm
| Arm | Count |
|---|---|
| Active rTMS Group 1 will receive high frequency repetitive transcranial magnetic stimulation (10hz-HF-rTMS) A total 14 sessions of HF-rTMS, 10 sessions daily (5 days/week, 2 weeks) and 4 sessions weekly (1 day/week, 4 weeks). | 10 |
| Sham rTMS Group 2 will receive sham stimulation. A total 14 sessions of sham-rTMS, 10 sessions daily (5 days/week, 2 weeks) and 4 sessions weekly (1 day/week, 4 weeks). | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Active rTMS | Sham rTMS | Total |
|---|---|---|---|
| Addenbrook Cognitive Examination Revised | 62.50 scores on a scale STANDARD_DEVIATION 18.8 | 76.90 scores on a scale STANDARD_DEVIATION 11.17 | 69.70 scores on a scale STANDARD_DEVIATION 16.76 |
| 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 | 10 Participants | 20 Participants |
| Age, Continuous | 46.70 years STANDARD_DEVIATION 9.06 | 43.80 years STANDARD_DEVIATION 9.37 | 45.25 years STANDARD_DEVIATION 9.08 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 10 Participants | 20 Participants |
| Fatigue Severity Scale | 5.28 scores on a scale STANDARD_DEVIATION 1.23 | 6.08 scores on a scale STANDARD_DEVIATION 1.11 | 5.68 scores on a scale STANDARD_DEVIATION 1.2 |
| Fibromyalgia Impact Questionnaire | 65.86 scores on a scale STANDARD_DEVIATION 8.27 | 66.44 scores on a scale STANDARD_DEVIATION 11.4 | 66.15 scores on a scale STANDARD_DEVIATION 9.69 |
| Hospital Anxiety and Depression Scale | 19.30 scores on a scale STANDARD_DEVIATION 8.14 | 22.90 scores on a scale STANDARD_DEVIATION 5.61 | 21.10 scores on a scale STANDARD_DEVIATION 7.04 |
| Region of Enrollment Turkey | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Visual Analog Scale-Pain | 7.20 units on a scale STANDARD_DEVIATION 1.75 | 7.40 units on a scale STANDARD_DEVIATION 1.35 | 7.30 units on a scale STANDARD_DEVIATION 1.52 |
| Visual Analog Scale-Stiffness | 7.40 units on a scale STANDARD_DEVIATION 1.58 | 7.60 units on a scale STANDARD_DEVIATION 1.17 | 7.50 units on a scale STANDARD_DEVIATION 1.35 |
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
Visual Analog Scale-Pain
The severity of the pain at rest was assessed on a 10 cm visual analog scale (Total score: 0-10)(0=no pain, 10=severe pain) Higher scores mean a worse outcome.
Time frame: in the second week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active rTMS | Visual Analog Scale-Pain | 5.30 units on a scale | Standard Deviation 2.11 |
| Sham rTMS | Visual Analog Scale-Pain | 6.80 units on a scale | Standard Deviation 1.69 |
Secondary
Fibromyalgia Impact Questionnaire
Functional health status and quality of life of the participants were assessed with the Fibromyalgia impact questionnaire, which measures 10 different features (physical functioning, missed days of work, depression, anxiety, feeling good, morning tiredness, pain, stiffness, fatigue, and well-being over the past week). The total Fibromyalgia impact questionnaire score is maximum 80 points. Higher scores indicate lower functionality level.
Time frame: in the sixth week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active rTMS | Fibromyalgia Impact Questionnaire | 51.71 score on a scale | Standard Deviation 22.17 |
| Sham rTMS | Fibromyalgia Impact Questionnaire | 56.02 score on a scale | Standard Deviation 22.57 |
Secondary
Visual Analog Scale-Pain
The severity of the pain at rest was assessed on a 10 cm visual analog scale (Total score: 0-10)(0=no pain, 10=severe pain) Higher scores mean a worse outcome.
Time frame: in the sixth week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active rTMS | Visual Analog Scale-Pain | 5.70 units on a scale | Standard Deviation 2.63 |
| Sham rTMS | Visual Analog Scale-Pain | 6.70 units on a scale | Standard Deviation 1.83 |
Other Pre-specified
Addenbrook Cognitive Examination Revised
Addenbrook Cognitive Examination-Revised is a brief cognitive test that consists of 5 basic sections: attention and orientation, memory, verbal fluency, language and visual-spatial abilities. Total score that can be obtained is 0-100. Higher scores are associated with a better cognitive state.
Time frame: in the sixth week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active rTMS | Addenbrook Cognitive Examination Revised | 66.50 score on a scale | Standard Deviation 19.67 |
| Sham rTMS | Addenbrook Cognitive Examination Revised | 81.40 score on a scale | Standard Deviation 7.79 |
Other Pre-specified
Fatigue Severity Scale
Severity of fatigue was evaluated with Fatigue severity scale, a 9-item self-report questionnaire scale. Each item of this scale consists of statements that are scored on a seven-point Likert type scale ranging from 1 to 7. Total Fatigue severity scale score is calculated as the mean value of nine items. Higher scores indicate higher fatigue severity. (Total score range: 1-7)
Time frame: in the sixth week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active rTMS | Fatigue Severity Scale | 4.89 score on a scale | Standard Deviation 1.59 |
| Sham rTMS | Fatigue Severity Scale | 5.39 score on a scale | Standard Deviation 1.62 |
Other Pre-specified
Fibromyalgia Impact Questionnaire
Functional health status and quality of life of the participants were assessed with the Fibromyalgia impact questionnaire, which measures 10 different features (physical functioning, missed days of work, depression, anxiety, feeling good, morning tiredness, pain, stiffness, fatigue, and well-being over the past week). The total Fibromyalgia impact questionnaire score is maximum 80 points. Higher scores indicate lower functionality level.
Time frame: in the second week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active rTMS | Fibromyalgia Impact Questionnaire | 48.35 score on a scale | Standard Deviation 16.64 |
| Sham rTMS | Fibromyalgia Impact Questionnaire | 54.39 score on a scale | Standard Deviation 15.47 |
Other Pre-specified
Hospital Anxiety and Depression Scale
Hospital anxiety and depression scale is an assessment tool developed to identify the risk of anxiety and depression and measure its level and change of severity. Its subscales are anxiety and depression. It contains 14 questions in total, including 7 (odd numbers) measuring anxiety and 7 (even numbers) measuring depression. The lowest and highest total score that a person can obtain from this scale are 0 and 42, respectively. High scores are associated with a worse psychiatric condition.
Time frame: in the sixth week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active rTMS | Hospital Anxiety and Depression Scale | 18.80 score on a scale | Standard Deviation 7.82 |
| Sham rTMS | Hospital Anxiety and Depression Scale | 17.60 score on a scale | Standard Deviation 10.68 |
Other Pre-specified
Visual Analog Scale-Stiffness
The severity of the stiffness at rest was assessed on a 10 cm visual analog scale (Total score: 0-10)(0=no stiffness, 10=severe stiffness) Higher scores mean a worse outcome.
Time frame: in the second week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active rTMS | Visual Analog Scale-Stiffness | 5.10 units on a scale | Standard Deviation 2.13 |
| Sham rTMS | Visual Analog Scale-Stiffness | 6.60 units on a scale | Standard Deviation 1.96 |