Home-based Transcranial Direct Current Stimulation (tDCS) Compared to Duloxetine: Non-inferiority Clinical Trial (FIBROSTIM)
FIBROSTIM
1 other identifier
interventional
610
1 country
1
Brief Summary
Fibromyalgia is characterized by widespread pain, fatigue, non-restorative sleep, and psychocognitive alterations, compromising quality of life and leading to absenteeism and early retirement. Up to 70% of patients discontinue treatment with antidepressants and anticonvulsants due to adverse effects or low efficacy, and more than 30% resort to opioid use. Given the treatment challenges and the scarcity of safe alternatives, there is growing interest in interventions such as transcranial direct current stimulation (tDCS), which has shown efficacy in improving symptoms and functionality, with low cost and few side effects. In this context, we designed a randomized, double-blind, double-dummy clinical trial to compare the non-inferiority of 28 home-based anodal tDCS (2 mA) applied over the primary motor cortex (M1) versus duloxetine 60 mg. Both treatments will be combined with physical exercise and pain education. Outcomes will be assessed through multidimensional measures of pain, functionality, global impression of improvement, and the function of the descending pain inhibitory system. Secondary outcomes include quality of life, depressive symptoms, psychophysical pain measures, and treatment adherence. An additional analysis will compare the results of sham tDCS and duloxetine placebo within the non-inferiority model. Predictors of treatment response will also be explored, including symptom severity and oscillatory patterns of cortical electrical activity, rest-activity rhythm, and autonomic function assessed by R-R interval. Furthermore, serum levels of S100-B protein, brain-derived neurotrophic factor (BDNF), and genetic variants related to neuroplasticity in the BDNF Val66Met, Catechol-O-Methyltransferase (COMT) (rs4680) (G\>A), OPRM1, and PER2 genes will be analyzed. Inflammatory markers (TNF-α, IL-1, IL-2, IL-6, IL-10, C-reactive protein) and serum endorphins will also be assessed. A total of 610 women with fibromyalgia (aged 18 to 75 years) will be randomized into three groups (2:2:1): duloxetine + sham tDCS (n=244); active tDCS + placebo (n=244); and sham tDCS + placebo (n=122). Participants will be assessed during treatment and at 3, 6, and 12 months after completing the intervention protocol. An interim analysis will be conducted when \~50% of participants (n ≈ 305) complete the 3-month follow-up by an independent, blinded Data Monitoring Committee (DMC). (i) The trial may be stopped if the conditional probability of demonstrating non-inferiority is \<10%, based on frequentist or Bayesian methods. (i) The trial will be stopped if serious adverse events (SAEs) in the active tDCS group increase by ≥30% compared to duloxetine (p \< 0.01, adjusted). (ii) Early stopping for efficacy will be considered if active tDCS demonstrates clear non-inferiority or superiority over duloxetine on the primary outcome. Superiority requires: (iii) a clinically relevant difference exceeding the non-inferiority margin (≥10% pain reduction); (ii) statistical significance (p \< 0.005, O'Brien-Fleming adjusted); and (iii) a ≥2-point (20%) improvement on the BPI, confirmed in the ITT analysis. This study aims to generate evidence to support the decision-making process of the National Committee for Health Technology Incorporation (CONITEC) regarding the availability of tDCS in the Brazilian Unified Health System (SUS). In addition, identifying predictors of response to tDCS and duloxetine, through the integration of genetic, neurophysiological, inflammatory, and psychosocial markers using machine learning algorithms, will allow for identifying factors that can personalize fibromyalgia treatment. This approach enhances clinical efficacy, reduces costs associated with ineffective interventions, and supports more accurate therapeutic decisions, expanding access to safe, effective, and sustainable care within the public healthcare system
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Sep 2025
Typical duration for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 4, 2025
CompletedStudy Start
First participant enrolled
September 30, 2025
CompletedFirst Posted
Study publicly available on registry
October 2, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2028
January 6, 2026
December 1, 2025
3.2 years
June 4, 2025
December 31, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Evaluation of Pain Interference
The Brief Pain Inventory (BPI) assesses pain intensity and interference across seven domains, generating a global interference index using 0-10 scales.
Participants will undergo weekly home-based assessments during both the run-in period (Weeks 1 to 3) and the treatment phase (Weeks 4 to 7), as well as at 3, 6, and 12 months after the end of the intervention
Patient Global Impression of Improvement
Patient Global Impression of Improvement (PGI-I): A 7-point scale that assesses the patient's overall perception of change in their condition, ranging from 'very much worse' (1) to 'very much improved' (7). Higher scores indicate greater perceived improvement (e.g., reduced symptoms or better functioning), while lower scores reflect worsening of symptoms or condition.
To be assessed at Visit 4, after completing the four-week treatment with either active (a-tDCS), s-tDCS), or duloxetine
Impact of fibromyalgia symptoms on quality of life
Fibromyalgia Impact Questionnaire (FIQ): Brazilian version assessing quality of life across function, overall impact, and symptoms. Scores range from 0 to 100, with higher scores indicating greater impact of fibromyalgia on the individual's daily life and functioning.
Participants will be assessed at Visit 1 (prior to the run-in period), at Visit 4 (after completing the four-week treatment with active [a-tDCS], sham [s-tDCS], or duloxetine), and again at 3, 6, and 12 months following the end of the treatment.
Cognitive symptoms
Barkley Deficits in Executive Functioning Scale (Short Form).Each item is rated on a Likert scale from 1 (never or rarely) to 4 (very often), resulting in a total score range of 20 to 80, with higher scores indicating greater executive functioning impairment
Participants will be assessed at Visit 1 (before the run-in period), at Visit 4 (after completing the four-week treatment with active [a-tDCS], sham [s-tDCS], or duloxetine), and again at 3, 6, and 12 months after the end of the treatment.
Function of the descending pain inhibitory system
Conditioned Pain Modulation (CPM) test: This test assesses descending pain inhibition. This test assesses the efficiency of descending pain inhibitory pathways. Pain intensity is rated using a verbal numerical rating scale (0 = no pain to 10 = worst possible pain) before (T0) and during (T1) cold-water immersion. The CPM effect is calculated as the difference between pain ratings at T0 and T1, with greater reductions indicating more effective pain inhibition.
Participants will be assessed at Visit 1 (before the run-in period) and at Visit 4 (after completing the four-week treatment with active [a-tDCS], sham [s-tDCS], or duloxetine).
Cortical Electrical Activity
Cortical electrical activity will be assessed using resting-state electroencephalography (EEG). Recordings will be performed in a quiet room, with participants seated comfortably and instructed to remain relaxed and still. EEG data will be collected during eyes-closed and eyes-open conditions using a 64-channel EEG system. Signals will be recorded with a band-pass filter of 0.3-200 Hz and a sampling rate of 250 Hz. Spectral power measures will be analyzed to characterize cortical oscillatory activity associated with pain processing and central sensitization in fibromyalgia.
Participants will be assessed at Visit 1 (before the run-in period) and at Visit 4 (after completing the four-week treatment with active [a-tDCS], sham [s-tDCS], or duloxetine).
Secondary Outcomes (18)
Depressive Symptoms
Assessment timepoints: Baseline; Week 8 (Visit 4/after completing the four-week treatment with active [a-tDCS], sham [s-tDCS], or duloxetine); 3 months post-treatment; 6 months post-treatment; 12 months post-treatment.
Subjective Sleep Quality
Assessment timepoints: Baseline; Week 8 (Visit 4/after completing the four-week treatment with active [a-tDCS], sham [s-tDCS], or duloxetine); 3 months post-treatment; 6 months post-treatment; 12 months post-treatment.
Circadian Profile (Chronotype)
Assessment timepoints: Baseline; Week 8 (Visit 4/after completing the four-week treatment with active [a-tDCS], sham [s-tDCS], or duloxetine); 3 months post-treatment; 6 months post-treatment; 12 months post-treatment.
Objective Sleep and Activity (Actigraphy)
Actigraph use during the run-in period (Weeks 1 to 3) and throughout the treatment phase (weeks 4 to 7)
Analgesic Use
Analgesic use during the run-in period (Weeks 1 to 3) and throughout the treatment phase (Weeks 4 to 7).
- +13 more secondary outcomes
Study Arms (3)
(s-tDCS over M1+placebo medication) - Home-Based Transcranial Direct Current Stimulation (tDCS)
SHAM COMPARATORThe sham tDCS protocol will use the same electrode montage as the active tDCS, with active current delivered for 30 seconds at the beginning, after 10 minutes, and at the end of the session. The current will be applied using 35 cm² electrodes.
The study includes 28 sessions of home-based anodal transcranial direct current stimulation (tDCS)
EXPERIMENTALActive anodal tDCS (2 mA) or sham tDCS will be applied over the left M1 (anode) and the right supraorbital area (cathode) for 20 minutes, combined with physical exercises and educational guidance on pain neuroscience for fibromyalgia. After in-person training, participants will receive instructions for home use.
Duloxetine 60 mg
ACTIVE COMPARATORThe pharmacological intervention will use duloxetine (30 mg and 60 mg), commercially acquired. The medication and placebo will be sourced via contracts with a compounding pharmacy and a retail drugstore. Generic Duloxetine Hydrochloride (Germed) will be purchased and sent for fractioning and placebo preparation. Each participant will receive a kit with four jars (duloxetine or placebo): Jar 01 (white lid): 7 × 30 mg - Week 1 (run-in); Jar 02 (green lid): 16 × 60 mg - Weeks 2-3 (run-in); Jar 03 (green lid): 42 × 60 mg - During tDCS; Jar 04 (white lid): 7 × 30 mg - Post-treatment taper.
Interventions
Duloxetine (30 mg and 60 mg) will be purchased from a commercial pharmacy and fractionated by a compounding pharmacy, which will also prepare the placebo. Capsules will be transferred into standardized jars based on dosing schedule: * Jar 01 (white cap): 7 capsules of 30 mg * Jar 02 (green cap): 16 capsules of 60 mg * Jar 03 (green cap): 42 capsules of 60 mg * Jar 04 (white cap): 7 capsules of 30 mg Placebo and duloxetine capsules will be identical in appearance. Kits will be labeled with CAEE number, participant ID (RedCap), pharmacist and PI names, and storage/use instructions. Kits will be stored at the HCPA Pharmacy Service under controlled conditions and dispensed during visits AV1 (Jars 1 and 2), AV2 (Jar 3), and AV3 (Jar 4).
Participants will be randomized to receive 28 sessions of active anodal tDCS (2 mA) or sham, with the anode over the left M1 and the cathode over the right supraorbital area, for 20 minutes, combined with pain neuroscience education and physical exercises. Sessions will be self-administered at home, daily for 4 weeks. Electrodes (35 cm²) will be placed using neoprene caps (sizes S to XL), adjusted according to head circumference. Monitoring: the device records session time, duration, and adherence, interrupting the session if impedance exceeds 1 mA (5-second interval) or if current varies \>10%. Developed in partnership with HCPA's Biomedical Engineering, the device is licensed by UFRGS/HCPA and registered with ANVISA (No. 80079190028).
Participants will be randomized to receive 28 sessions of active anodal tDCS (2 mA) anode over the left M1 and the cathode over the right supraorbital area, for 20 minutes
Duloxetine (30 mg and 60 mg) will be purchased from a commercial pharmacy and fractionated by a compounding pharmacy, which will also prepare the placebo. Capsules will be transferred into standardized jars based on dosing schedule: * Jar 01 (white cap): 7 capsules of 30 mg * Jar 02 (green cap): 16 capsules of 60 mg * Jar 03 (green cap): 42 capsules of 60 mg * Jar 04 (white cap): 7 capsules of 30 mg Placebo and duloxetine capsules will be identical in appearance. Kits will be labeled with CAEE number, participant ID (RedCap), pharmacist and PI names, and storage/use instructions. Kits will be stored at the HCPA Pharmacy Service under controlled conditions and dispensed during visits AV1 (Jars 1 and 2), AV2 (Jar 3), and AV3 (Jar 4).
Eligibility Criteria
You may qualify if:
- Woman aged between 18 and 75 years
- Right-handed
- Literate in reading and writing
- Clinical diagnosis of fibromyalgia based on the American College of Rheumatology (ACR) 2010-2016 criteria
- Numeric Pain Scale (NPS) score ≥ 4 on most days in the past 30 days
- Agree no changes in medication dosage during the treatment period (except for analgesics)
- Able to swallow tablets
- Able to understand instructions for using tDCS at home
You may not qualify if:
- Living more than 250 km from Porto Alegre
- Pregnancy
- Decompensated systemic diseases
- Chronic inflammatory rheumatologic diseases
- Untreated hypothyroidism
- Active cancer under treatment
- Alcohol or drug abuse in the past 6 months
- Decompensated psychiatric disorders with suicide risk and a defined plan
- Use of duloxetine at a dose \> 60 mg/day
- Metal implants in the brain
- Implanted brain medical devices
- Cardiac pacemaker
- Cochlear implant
- Neurological disorders
- History of traumatic brain injury or neurosurgery
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil
Related Publications (7)
Yousefi Soorani L, Shafiei Bafti B, Homam SM, Abbasloo Z, Taghizadeh Zanooghi H. Hypogene enrichment in Miduk porphyry copper ore deposit, Iran. Sci Rep. 2022 Nov 9;12(1):19133. doi: 10.1038/s41598-022-23501-5.
PMID: 36352022RESULTJornada MND, Antunes LC, Alves C, Torres ILS, Fregni F, S Sanches PR, P Silva D Jr, Caumo W. Impact of multiple-session home-based transcranial direct current stimulation (M-HB-tDCS) on eating behavior in fibromyalgia: A factorial randomized clinical trial. Brain Stimul. 2024 Mar-Apr;17(2):152-162. doi: 10.1016/j.brs.2024.02.001. Epub 2024 Feb 8.
PMID: 38336340RESULTFregni F, El-Hagrassy MM, Pacheco-Barrios K, Carvalho S, Leite J, Simis M, Brunelin J, Nakamura-Palacios EM, Marangolo P, Venkatasubramanian G, San-Juan D, Caumo W, Bikson M, Brunoni AR; Neuromodulation Center Working Group. Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders. Int J Neuropsychopharmacol. 2021 Apr 21;24(4):256-313. doi: 10.1093/ijnp/pyaa051.
PMID: 32710772RESULTCaumo W, Lopes Ramos R, Vicuna Serrano P, da Silveira Alves CF, Medeiros L, Ramalho L, Tomeddi R, Bruck S, Boher L, Sanches PRS, Silva DP Jr, Ls Torres I, Fregni F. Efficacy of Home-Based Transcranial Direct Current Stimulation Over the Primary Motor Cortex and Dorsolateral Prefrontal Cortex in the Disability Due to Pain in Fibromyalgia: A Factorial Sham-Randomized Clinical Study. J Pain. 2024 Feb;25(2):376-392. doi: 10.1016/j.jpain.2023.09.001. Epub 2023 Sep 7.
PMID: 37689323RESULTCaumo W, Deitos A, Carvalho S, Leite J, Carvalho F, Dussan-Sarria JA, Lopes Tarrago Mda G, Souza A, Torres IL, Fregni F. Motor Cortex Excitability and BDNF Levels in Chronic Musculoskeletal Pain According to Structural Pathology. Front Hum Neurosci. 2016 Jul 15;10:357. doi: 10.3389/fnhum.2016.00357. eCollection 2016.
PMID: 27471458RESULTCaumo W, Alves RL, Vicuna P, Alves CFDS, Ramalho L, Sanches PRS, Silva DP, da Silva Torres IL, Fregni F. Impact of Bifrontal Home-Based Transcranial Direct Current Stimulation in Pain Catastrophizing and Disability due to Pain in Fibromyalgia: A Randomized, Double-Blind Sham-Controlled Study. J Pain. 2022 Apr;23(4):641-656. doi: 10.1016/j.jpain.2021.11.002. Epub 2021 Nov 13.
PMID: 34785366RESULTBrietzke AP, Zortea M, Carvalho F, Sanches PRS, Silva DPJ, Torres ILDS, Fregni F, Caumo W. Large Treatment Effect With Extended Home-Based Transcranial Direct Current Stimulation Over Dorsolateral Prefrontal Cortex in Fibromyalgia: A Proof of Concept Sham-Randomized Clinical Study. J Pain. 2020 Jan-Feb;21(1-2):212-224. doi: 10.1016/j.jpain.2019.06.013. Epub 2019 Jul 26.
PMID: 31356985RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Researchers will receive a tDCS device pre-programmed by biomedical engineering, without prior knowledge of whether the condition is active or sham. The compounding pharmacy contracted for the study will prepare the placebo and fractionate the Duloxetine Hydrochloride. Researchers will receive a kit containing four labeled containers: Containers 1 and 4 (white lid): 7 capsules of either placebo or Duloxetine 30 mg Container 2 (green lid): 16 capsules of either placebo or Duloxetine 60 mg Container 3 (green lid): 42 capsules of either placebo or Duloxetine 60 mg Each container will display the randomization ID and will be properly labeled. Allocation information will be accessible only to the responsible pharmacist (who is not involved in data collection) and the researcher who performed the randomization (with no contact with participants). Labels will include the project number (CAAE), participant ID (RedCap), and pharmacist's name.
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 4, 2025
First Posted
October 2, 2025
Study Start
September 30, 2025
Primary Completion (Estimated)
December 1, 2028
Study Completion (Estimated)
December 1, 2028
Last Updated
January 6, 2026
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- When available: With publication of primary outcomes
- Access Criteria
- Data will be available upon request at wcaumo@hcpa.edu.br after 6 months of publication
Data will be available upon request at wcaumo@hcpa.edu.br after 6 months of publication Data available: Yes. When available: With publication. Data types: Deidentified participant data, Data dictionary. Additional Information Who can access the data: Anyone requesting the data. Types of analyses: For any purpose. Mechanisms of data availability: Without investigator support.