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Repetitive Transcranial Magnetic Stimulation (rTMS) in Fibromyalgia

Sponsor
Izmir Katip Celebi University (Other)
Overall Status
Completed
CT.gov ID
NCT03909009
Collaborator
(none)
20
Enrollment
1
Location
2
Arms
12
Actual Duration (Months)
1.7
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
  • Device: rTMS + Neuronavigation
 N/A

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Pain, Fatigue, Quality of Life, Cognitive Function and Mood in Fibromyalgia
Actual Study Start Date :
Apr 11, 2019
Actual Primary Completion Date :
Apr 1, 2020
Actual Study Completion Date :
Apr 10, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: 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).

Device: rTMS + Neuronavigation
Repetitive Transcranial Magnetic Stimulation (Neuro-MS/D) + Neural Navigator
Sham Comparator: 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).

Device: rTMS + Neuronavigation
Repetitive Transcranial Magnetic Stimulation (Neuro-MS/D) + Neural Navigator

Outcome Measures

Primary Outcome Measures

  1. 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 Outcome Measures

  1. 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.

  2. 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 Outcome Measures

  1. 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.

  2. 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.

  3. 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)

  4. 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.

  5. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Izmir Katip Çelebi University Faculty of Medicine, Department of Physical Medicine and Rehabilitation İzmir Turkey 35290

Sponsors and Collaborators

  • Izmir Katip Celebi University

Investigators

  • Study Director: Ayhan Aşkın, Assoc. Prof., Izmir Katip Çelebi University Faculty of Medicine

Study Documents (Full-Text)

More Information

Publications

Responsible Party:
İbrahim Bilir, Principal Investigator, Izmir Katip Celebi University
ClinicalTrials.gov Identifier:
NCT03909009
Other Study ID Numbers:
  • 14032019
First Posted:
Apr 9, 2019
Last Update Posted:
Jun 16, 2020
Last Verified:
Jun 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by İbrahim Bilir, Principal Investigator, Izmir Katip Celebi University
Fibromyalgia, neuronavigated-rTMS, pain, stiffness, fatigue
Additional relevant MeSH terms:
Fibromyalgia
Myofascial Pain Syndromes

Study Results

Participant Flow

Recruitment Details Participants were recruited from Physical Medicine and Rehabilitation (PMR) outpatient clinics of a university hospital.
Pre-assignment Detail Twenty-eight patients were evaluated for participation in the study. Eight patients were excluded.
Arm/Group Title Active rTMS Sham rTMS
Arm/Group Description 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).
Period Title: Overall Study
STARTED 10 10
COMPLETED 10 10
NOT COMPLETED 0 0

Baseline Characteristics

Arm/Group Title Active rTMS Sham rTMS Total
Arm/Group Description 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). Total of all reporting groups
Overall Participants 10 10 20
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
Between 18 and 65 years
10
100%
10
100%
20
100%
>=65 years
0
0%
0
0%
0
0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
46.70
(9.06)
43.80
(9.37)
45.25
(9.08)
Sex: Female, Male (Count of Participants)
Female
10
100%
10
100%
20
100%
Male
0
0%
0
0%
0
0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
0
0%
0
0%
Not Hispanic or Latino
0
0%
0
0%
0
0%
Unknown or Not Reported
10
100%
10
100%
20
100%
Region of Enrollment (Count of Participants)
Turkey
10
100%
10
100%
20
100%
Visual Analog Scale-Pain (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]
7.20
(1.75)
7.40
(1.35)
7.30
(1.52)
Visual Analog Scale-Stiffness (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]
7.40
(1.58)
7.60
(1.17)
7.50
(1.35)
Fibromyalgia Impact Questionnaire (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]
65.86
(8.27)
66.44
(11.40)
66.15
(9.69)
Fatigue Severity Scale (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]
5.28
(1.23)
6.08
(1.11)
5.68
(1.20)
Hospital Anxiety and Depression Scale (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]
19.30
(8.14)
22.90
(5.61)
21.10
(7.04)
Addenbrook Cognitive Examination Revised (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]
62.50
(18.80)
76.90
(11.17)
69.70
(16.76)

Outcome Measures

1. Primary Outcome
Title Visual Analog Scale-Pain
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Active rTMS Sham rTMS
Arm/Group Description 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).
Measure Participants 10 10
Mean (Standard Deviation) [units on a scale]
5.30
(2.11)
6.80
(1.69)
2. Secondary Outcome
Title Visual Analog Scale-Pain
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Active rTMS Sham rTMS
Arm/Group Description 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).
Measure Participants 10 10
Mean (Standard Deviation) [units on a scale]
5.70
(2.63)
6.70
(1.83)
3. Secondary Outcome
Title Fibromyalgia Impact Questionnaire
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Active rTMS Sham rTMS
Arm/Group Description 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).
Measure Participants 10 10
Mean (Standard Deviation) [score on a scale]
51.71
(22.17)
56.02
(22.57)
4. Other Pre-specified Outcome
Title Visual Analog Scale-Stiffness
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Active rTMS Sham rTMS
Arm/Group Description 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).
Measure Participants 10 10
Mean (Standard Deviation) [units on a scale]
5.10
(2.13)
6.60
(1.96)
5. Other Pre-specified Outcome
Title Fibromyalgia Impact Questionnaire
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Active rTMS Sham rTMS
Arm/Group Description 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).
Measure Participants 10 10
Mean (Standard Deviation) [score on a scale]
48.35
(16.64)
54.39
(15.47)
6. Other Pre-specified Outcome
Title Fatigue Severity Scale
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Active rTMS Sham rTMS
Arm/Group Description 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).
Measure Participants 10 10
Mean (Standard Deviation) [score on a scale]
4.89
(1.59)
5.39
(1.62)
7. Other Pre-specified Outcome
Title Hospital Anxiety and Depression Scale
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Active rTMS Sham rTMS
Arm/Group Description 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).
Measure Participants 10 10
Mean (Standard Deviation) [score on a scale]
18.80
(7.82)
17.60
(10.68)
8. Other Pre-specified Outcome
Title Addenbrook Cognitive Examination Revised
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Active rTMS Sham rTMS
Arm/Group Description 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).
Measure Participants 10 10
Mean (Standard Deviation) [score on a scale]
66.50
(19.67)
81.40
(7.79)

Adverse Events

Time Frame 6 weeks (Between the start of the study and the day when the last outcome measure is evaluated)
Adverse Event Reporting Description
Arm/Group Title Active rTMS Sham rTMS
Arm/Group Description Group 1 will receive HF rTMS treatment daily from Monday to Friday in first 2 weeks. After first 2 weeks there will be sessions once a week for 1 month. There will be 14 sessions in total. rTMS + Neuronavigation: Repetitive Transcranial Magnetic Stimulation (Neuro-MS/D) + Neural Navigator Group 2 will receive sham daily from Monday to Friday in first 2 weeks. After first 2 weeks there will be sessions once a week for 1 month. There will be 14 sham sessions in total. rTMS + Neuronavigation: Repetitive Transcranial Magnetic Stimulation (Neuro-MS/D) + Neural Navigator
All Cause Mortality
Active rTMS Sham rTMS
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/10 (0%) 0/10 (0%)
Serious Adverse Events
Active rTMS Sham rTMS
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/10 (0%) 0/10 (0%)
Other (Not Including Serious) Adverse Events
Active rTMS Sham rTMS
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/10 (0%) 0/10 (0%)

Limitations/Caveats

Current study has several limitations: First is the relatively small sample size. Second, we didn't use sham stimulation probe. Third, our patients only consisted of female gender.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Doç.Dr. Ayhan AŞKIN
Organization Izmir Katip Çelebi University, Faculty of Medicine
Phone 00902322444444 ext 1529
Email ayhanaskin@hotmail.com
Responsible Party:
İbrahim Bilir, Principal Investigator, Izmir Katip Celebi University
ClinicalTrials.gov Identifier:
NCT03909009
Other Study ID Numbers:
  • 14032019
First Posted:
Apr 9, 2019
Last Update Posted:
Jun 16, 2020
Last Verified:
Jun 1, 2020