The Added Value of Transcranial Direct Current Stimulation (tDCS) During Exercise for People With Chronic Widespread Pain

NCT07212829 | Recruiting DMC

• 1 other identifier: EC-2025-255
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Many people with chronic widespread pain (CWP) feel more pain and fatigue after exercise. This makes it hard to stay active. Unfortunately, the investigators do not fully understand why this happens and how to prevent it. The primary goal of this study is to explore the underlying genetic and epigenetic mechanisms of BDNF gene in response to exercise, and investigate if transcranial direct current stimulation (tDCS) during exercise works to improve worsening symptoms response to exercise in people with CWP. The investigators designed a randomized crossover study and will enroll 60 patients with CWP and 60 healthy controls. Participants will undergo 2 interventions in random order: 1) exercise + active tDCS, and 2) exercise + sham tDCS. Participants will visit the hospital twice with at least one week in between the visits.

Conditions

Chronic Widespread Pain; Fibromyalgia (FM)

Keywords

BDNF; pain; exercise; DNA methylation

Outcome Measures

Primary Outcomes (3)

• Pain intensity

  Pain intensity is measured using a 0-10 Numeric Rating Scale (NRS), where 0 indicates "no pain" and 10 indicates "the worst pain imaginable".

  Participants rate their pain at baseline, and 30 minutes after the intervention.

• Blood BDNF levels

  Venous blood samples are collected before and after each exercise-tDCS session. Samples are centrifuged, aliquoted, and stored at -80 °C until analysis. Blood levels of brain-derived neurotrophic factor (BDNF) are quantified using a commercially available enzyme-linked immunosorbent assay (ELISA), following the manufacturer's instructions.

  Blood samples are collected at baseline and 20 minutes after exercise-tDCS session.

• BDNF DNA methylation

  Genomic DNA is extracted from whole blood collected at baseline and after the intervention. DNA methylation of the BDNF gene is assessed using bisulfite conversion followed by quantitative analysis of methylation levels at CpG sites within promoter regions previously associated with pain regulation. Methylation levels are expressed as the percentage of methylated cytosines at each CpG site. Changes in DNA methylation are calculated as the difference between post-intervention and baseline values.

  Blood samples are collected at baseline and 20 minutes after exercise-tDCS session.

Secondary Outcomes (6)

• Pain intensity

  Participants rate their pain at immediately, 8 hours, 24 hours, 48 hours, and 7 days after the intervention.

• Fatigue

  Participants rate their fatigue at baseline, and 24 hours, 48 hours, 7 days after the intervention.

• Fibromyalgia symptom impact

  Participants rate their FIQR at baseline, and 7 days after intervention.

• Central sensitization symptoms

  Participants rate their CSI at baseline.

• Pain catastrophizing

  Participants rate their PCS at baseline, and 30 minutes after the intervention.

Study Arms (4)

Exercise + active tDCS + patients

EXPERIMENTAL

Patient participants will receive one bout of submaximal aerobic exercise, along with a single session of active tDCS simultaneously.

Device: Active tDCS; Behavioral: Aerobic exercise

Exercise + sham tDCS + patients

SHAM COMPARATOR

Patient participants will receive one bout of submaximal aerobic exercise, along with a single session of sham tDCS simultaneously.

Behavioral: Aerobic exercise; Device: Sham tDCS

Exercise + active tDCS + healthy controls

ACTIVE COMPARATOR

healthy volunteer participants will receive one bout of submaximal aerobic exercise, along with a single session of active tDCS simultaneously.

Device: Active tDCS; Behavioral: Aerobic exercise

Exercise + sham tDCS + healthy controls

SHAM COMPARATOR

healthy volunteer participants will receive one bout of submaximal aerobic exercise, along with a single session of sham tDCS simultaneously.

Behavioral: Aerobic exercise; Device: Sham tDCS

Interventions

Active tDCS DEVICE

tDCS is performed using a monophasic current device. Pairs of silicon sponge sur-face electrodes (35 cm2) are soaked in saline and positioned as follows: the anode is placed over the region of the dorsolateral prefrontal cortex (DLPFC) per the international 10/20 system at point F3 (left DLPFC), and the cathode is placed on the contralateral supraorbital area (FP2 site). For active tDCS, the current is ramped up for 30 seconds until the center electrode reaches a target intensity of 2 mA, then remains for 29 minutes before dropping for another 30s.

Exercise + active tDCS + healthy controls; Exercise + active tDCS + patients

Aerobic exercise BEHAVIORAL

Participants will perform a moderate aerobic exercise (AE, known as aerobic power index), using a cycle er-gometer. The exercise intensity is moderate and individually tailored based on each participant's estimated maximum heart rate (HRmax), calculated using the validated formula: HRmax = 211 - (0.64 × age).

Exercise + active tDCS + healthy controls; Exercise + active tDCS + patients; Exercise + sham tDCS + healthy controls; Exercise + sham tDCS + patients

Sham tDCS DEVICE

tDCS is performed using a monophasic current device. Pairs of silicon sponge sur-face electrodes (35 cm2) are soaked in saline and positioned as follows: the anode is placed over the region of the dorsolateral prefrontal cortex (DLPFC) per the international 10/20 system at point F3 (left DLPFC), and the cathode is placed on the contralateral supraorbital area (FP2 site). In the sham condition, current is ramped up to 2.0 mA for 30 seconds and then ramped down to 0 mA, with the total session duration matched to the active condition. This procedure was used to mimic the tingling sensa-tions typically experienced at the beginning of stimulation. Participants received identical instructions, session timing, and room setup across conditions.

Exercise + sham tDCS + healthy controls; Exercise + sham tDCS + patients

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients
• Participants in the patient group must meet all of the following criteria:
• Diagnosis of chronic widespread pain (CWP) or fibromyalgia;
• Age between 18 and 70 years old;
• Body mass index (BMI) ≤ 35;
• Widespread Pain Index (WPI) assessment: the WPI questionnaire (0-19 points) will be used to record the number and distribution of painful body sites. Participants will be classified as having CWP if pain is reported on both sides of the body, above and below the waist, and in the axial skeleton, with pain symptoms lasting ≥ 3 months;
• Stable medication use for at least 1 month prior to study entry.
• Healthy control group
• Participants in the healthy control group must meet all of the following criteria:
• Age between 18 and 70 years old;
• Body mass index (BMI) ≤ 35;
• No chronic conditions, such as chronic pain and diabetes.

You may not qualify if:

• For both patients and healthy controls, participants will be excluded if they meet any of the following:
• Current pregnancy or pregnancy within the past 12 months;
• Contraindications for non-invasive brain stimulation (NIBS), in line with published safety guidelines;
• History of neurological disorders, including epilepsy (personal or family history), traumatic brain injury, stroke, dementia, or Parkinson's disease;
• Major medical conditions, including cancer, endocrine or metabolic disorders, urine, genital and cardiovascu-lar diseases (e.g., myocardial infarction, heart failure, arrhythmia, uncontrolled hypertension).
• Substance abuse.
• Presence of psychiatric disorders other than depression or anxiety.

Sponsors & Collaborators

• Vrije Universiteit Brussel: lead

Study Sites (1)

VUB

Jette, 1090, Belgium

RECRUITING

MeSH Terms

Conditions

Chronic Pain; Fibromyalgia; Pain; Motor Activity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Pain in Motion research group

CONTACT

+32 497783956; huanyu.xiong@vub.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 1, 2025
• First Posted: October 8, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: April 20, 2026

Record last verified: 2025-09

Locations

BE (1)