Optimized tDCS for Fibromyalgia: Targeting the Endogenous Pain Control System

NCT03371225 | Completed Results DMC FDA Device

• 1 other identifier: 2017P002524
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

This trial aims at understanding the mechanisms of optimized transcranial direct current stimulation (tDCS) (16 tDCS sessions combined with exercise)\] on pain control. Optimized tDCS can lead to stronger engagement of the endogenous pain regulatory system that will ultimately lead to increased pain relief in patients with fibromyalgia (FM). Therefore, the investigators designed a 2x2 factorial mechanistic trial \[tDCS (active and sham) and aerobic exercise (AE) (active and control)\] to evaluate the effects of 4 weeks of tDCS coupled with exercise on the endogenous pain regulatory system assessed by conditioned pain modulation (CPM) and central sensitization as assessed by temporal slow pain summation (TSPS), and compared to either intervention alone and to no intervention.

Conditions

Fibromyalgia

Outcome Measures

Primary Outcomes (2)

• Conditioning Pain Modulation (CPM)

  Pain intensity was measured using the Numeric Pain Scale (NPS; 0 = no pain, 10 = worst pain). Higher scores indicate worse pain. A "pain-6 temperature" was first identified (temperature that elicits NPS = 6). Test stimulus: Pain-6 temperature applied for 30s; participants rated pain at 10, 20, and 30s. The test-stimulus score is the average of the three NPS ratings. Conditioned stimulus: After 5 minutes, the left hand was immersed in 10-12°C water for 30s while the same pain-6 temperature was applied again. Pain was rated the same way, and the conditioned-stimulus score is the average of the three NPS ratings. CPM calculation = (test-stimulus average) - (conditioned-stimulus average). Positive values = better endogenous pain inhibition; negative values = worse.

  6 weeks

• Temporal Slow Pain Summation (TSPS)

  Participants first determined the temperature that elicited Numeric Pain Scale (NPS) = 6 ("pain-6"). Using this temperature, a train of 15 heat pulses (0.4 Hz) was delivered to the right forearm with a TSA-II thermode. Pain was rated using the NPS after the 1st and 15th heat stimulus. TSPS calculation: TSPS = NPS rating after the 15th stimulus - NPS rating after the 1st stimulus. Higher TSPS values represent greater temporal pain summation (worse outcome).

  6 weeks

Study Arms (4)

Active tDCS and Active Exercise

EXPERIMENTAL

Active tDCS for 20 min Active exercise (60-70% max HR) for 30 min

Device: Active tDCS; Procedure: Active Exercise

Sham tDCS and Active Exercise

ACTIVE COMPARATOR

Sham tDCS for 20 min Active exercise (60-70% max HR) for 30 min

Procedure: Active Exercise; Device: Sham tDCS

Active tDCS and Sham Exercise

ACTIVE COMPARATOR

Active tDCS for 20 min Sham exercise (within 10% baseline HR) for 30 min

Device: Active tDCS; Procedure: Sham Exercise

Sham TDCS and Sham Exercise

SHAM COMPARATOR

Sham tDCS for 20 min Sham exercise (within 10% baseline HR) for 30 min

Device: Sham tDCS; Procedure: Sham Exercise

Interventions

Active tDCS DEVICE

Active tDCS: A 1x1 Low-intensity DC Stimulator will be used to deliver direct current through rubber electrodes in saline soaked sponges. The anode will be placed over the left primary motor cortex (M1) while the cathode will be placed over the contralateral supra-orbital area. 20 minutes of tDCS will be applied.

Also known as: tDCS

Active tDCS and Active Exercise; Active tDCS and Sham Exercise

Active Exercise PROCEDURE

Participants will walk briskly in a treadmill (as to keep at 60-70% maximum heart rate) for 30 minutes

Also known as: Aerobic Exercises

Active tDCS and Active Exercise; Sham tDCS and Active Exercise

Sham tDCS DEVICE

Active tDCS: A 1x1 Low-intensity DC Stimulator will be used to deliver direct current through rubber electrodes in saline soaked sponges. The anode will be placed over the left primary motor cortex (M1) while the cathode will be placed over the contralateral supra-orbital area. Only 30 seconds of current will be applied for the sham condition.

Also known as: Placebo tDCS

Sham TDCS and Sham Exercise; Sham tDCS and Active Exercise

Sham Exercise PROCEDURE

Participants will walk in a treadmill (as to keep at 10% within their baseline heart rate) for 30 minutes.

Also known as: Placebo Aerobic Exercise

Active tDCS and Sham Exercise; Sham TDCS and Sham Exercise

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age range 18-65 years,
• Diagnosis of FM pain according to the ACR 2010 criteria (existing pain for more than 6 months with an average of at least 4 on a 0-10 VAS scale) without other comorbid chronic pain diagnosis,
• Pain resistant to common analgesics and medications for chronic pain such as Tylenol, Aspirin, Ibuprofen, Soma, Parafon Forte DCS, Zanaflex, and Codeine,
• Must have the ability to feel sensation by Von-Frey fiber on the forearm,
• Able to provide informed consent to participate in the study.

You may not qualify if:

• Clinically significant or unstable medical or psychiatric disorder,
• history of substance abuse within the past 6 months as self-reported (if subject reports a history of substance abuse, we will confirm using DSM V criteria),
• Previous significant neurological history (e.g., traumatic brain injury), resulting in neurological deficits, such as cognitive or motor deficits, as self-reported,
• Previous neurosurgical procedure with craniotomy,
• Severe depression (If a patient scores \>30 on the Beck Depression Inventory, one will obtain clearance. If one does not pass the medical clearance, one will not be included in the study)
• Pregnancy (as the safety of tDCS in pregnant population (and children) has not been assessed (though risk is non-significant), the investigators will exclude pregnant women (and children). Women of child-bearing potential will be required to take a urine pregnancy test during the screening process and at every week of stimulation),
• Current opiate use in large doses (more than 30mg of oxycodone/hydrocodone or 7.5mg of hydromorphone (Dilaudid) or equivalent),
• Patients will be excluded when they have increased risk for exercise

Sponsors & Collaborators

• Spaulding Rehabilitation Hospital: lead

Study Sites (1)

Spaulding Rehabilitation Hospital for Continuing Care

Cambridge, Massachusetts, 02138, United States

Location

Related Publications (2)

• Pacheco-Barrios K, Teixeira PEP, Martinez-Magallanes D, Neto MS, Pichardo EA, Camargo L, Lima D, Cardenas-Rojas A, Fregni F. Brain compensatory mechanisms in depression and memory complaints in fibromyalgia: the role of theta oscillatory activity. Pain Med. 2024 Aug 1;25(8):514-522. doi: 10.1093/pm/pnae030.

  PMID: 38652585 DERIVED

• Castelo-Branco L, Uygur Kucukseymen E, Duarte D, El-Hagrassy MM, Bonin Pinto C, Gunduz ME, Cardenas-Rojas A, Pacheco-Barrios K, Yang Y, Gonzalez-Mego P, Estudillo-Guerra A, Candido-Santos L, Mesia-Toledo I, Rafferty H, Caumo W, Fregni F. Optimised transcranial direct current stimulation (tDCS) for fibromyalgia-targeting the endogenous pain control system: a randomised, double-blind, factorial clinical trial protocol. BMJ Open. 2019 Oct 30;9(10):e032710. doi: 10.1136/bmjopen-2019-032710.

  PMID: 31672712 DERIVED

MeSH Terms

Conditions

Fibromyalgia

Interventions

Transcranial Direct Current Stimulation; Muscle Stretching Exercises; Exercise

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Physical Therapy Modalities; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Results Point of Contact

• Title: Felipe Fregni
• Organization: Spaulding Rehabilitation Hospital

fregni.felipe@mgh.harvard.edu

6179526154

Study Officials

• Felipe Fregni, MD PhD MPH

  Spaulding Rehabilitation Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Spaulding Neuromodulation Center

Study Record Dates

• First Submitted: November 20, 2017
• First Posted: December 13, 2017
• Study Start: May 1, 2019
• Primary Completion: September 26, 2024
• Study Completion: October 26, 2025
• Last Updated: December 10, 2025
• Results First Posted: December 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (1)