Multisite Transcutaneous Electrical Nerve Stimulation in Fibromyalgia: A Randomized, Double-Blind, Sham-Controlled Crossover Trial Comparing Two Stimulation Modalities

• EXOPULSE Mollii Suit (Device): The Exopulse Mollii Suit is a CE-marked neuromodulation device with a favorable safety profile, good tolerability, and ease of use. Developed by Exoneural Network AB, the device consists of a full-body garment incorporating 58 electrodes capable of delivering transcutaneous electrical stimulation to 40 muscle groups using low-frequency (20 Hz), low-intensity electrical currents (current intensity: 2 mA; pulse width: 25-170 µs). The stimulation is not intended to induce muscle contraction but rather to modulate pain processing through activation of large-diameter afferent fibers, thereby reducing nociceptive transmission in accordance with the gate control theory of pain. The device is intended for pain reduction and is used as a daily, non-pharmacological neuromodulation intervention.

Primary outcomes

• Change from baseline in functional disability as assessed using the Fibromyalgia Impact Questionnaire scores [before the first intervention (week 1), end of the first intervention (week 5), before the second intervention (weekd 7), after the second intervention (week 11), before the third intervention (week 13), and after the third intervention (week 17)]: The primary endpoint is the change in functional disability assessed using the Fibromyalgia Impact Questionnaire across the three stimulation conditions (Condition A, Condition B and sham stimulation). The scores ranges from a minimal score of 0 to a maximal score of 100, with higher scores reflecting a greater impact of fibromyalgia.

Secondary outcomes

• Change from baseline in pain intensity as assessed using the Visual Analogue Scale for pain [before the first intervention (week 1), end of the first intervention (week 5), before the second intervention (weekd 7), after the second intervention (week 11), before the third intervention (week 13), and after the third intervention (week 17)]: Visual Analogue scale of Pain consists of rating the symptom on a 10 cm horizontal line going from 0 meaning "no pain" to 10 meaning "worst pain imaginable". It has good psychometric properties for assessing pain and has a high sensibility and sensitivity and a good discriminative power in patients with fibromyalgia.
• Change from baseline in pain severity and pain interference, assessed using the Brief Pain Inventory [before the first intervention (week 1), end of the first intervention (week 5), before the second intervention (weekd 7), after the second intervention (week 11), before the third intervention (week 13), and after the third intervention (week 17)]: The validated French version of the Brief Pain Inventory will be used to assess pain severity (4 items) and pain interference (7 items) (Cronbach's alpha ranging from 0.86 to 0.90). Brief Pain Inventory items are rated on a 10-point scale running from 0 (no pain/does not interfere) to 10 (pain as bad as you can/interferes completely).
• Change from baseline in pain catastrophizing, assessed using the Pain Catastrophizing Scale [before the first intervention (week 1), end of the first intervention (week 5), before the second intervention (weekd 7), after the second intervention (week 11), before the third intervention (week 13), and after the third intervention (week 17)]: The Pain Catastrophizing Scale will also be employed, it is a valid and reliable scale that includes 13 items assessing the presence and severity of feelings or thoughts that emerge when experiencing pain. Each item is rated on a 5-point Likert scale ranging from 0 (not at all) to 4 (all the time). The total score ranges from a minimum of 0 to a maximum of 52 with a higher score reflecting worse condition. It is possible to calculate a total and three subscale scores (i.e., helplessness, magnification, and rumination) . The total PCS has good psychometric properties: internal consistency (Cronbach's alpha =0.91) and test-retest reliability (r=0.85 at two weeks and r=0.77 at six weeks).
• Change from baseline in fatigue as assessed using the Visual Analogue Scale for fatigue [before the first intervention (week 1), end of the first intervention (week 5), before the second intervention (weekd 7), after the second intervention (week 11), before the third intervention (week 13), and after the third intervention (week 17)]: The visual Analogue Scale for fatigue consists of rating the symptom on a 10 cm horizontal line going from a minimum of 0 reflecting "no fatigue" to a maximum of 10 reflecting the "worst fatigue imaginable". It has good psychometric properties for assessing fatigue and has a high sensibility and sensitivity and a good discriminative power
• Change from baseline in anxiety and depression symptoms, assessed using the Hospital Anxiety and Depression Scale [before the first intervention (week 1), end of the first intervention (week 5), before the second intervention (weekd 7), after the second intervention (week 11), before the third intervention (week 13), and after the third intervention (week 17)]: The Hospital Anxiety and Depression Scale is a 14-item generic scale with good psychometric properties. It consists of seven items assessing anxiety and seven others assessing depression. Scores can range from 0 to 21 on each subscale, with higher scores indicating worse symptomatology.
• Change from baseline in global sleep quality, assessed using the Pittsburgh Sleep Quality Index [before the first intervention (week 1), end of the first intervention (week 5), before the second intervention (weekd 7), after the second intervention (week 11), before the third intervention (week 13), and after the third intervention (week 17)]: The Pittsburgh Sleep Quality Index is a self-rated questionnaire that evaluates sleep quality. Its 19 questions aim to assess the sleep pattern during the previous month. Scores can range from a minimum of 0 (better sleep quality) to a maximum of 21 (worse sleep quality). This scale has good psychometric properties and its utility in clinical practice and research activities has been proven.
• Change from baseline in subjective sleep experience, assessed using the Leeds Sleep Evaluation Questionnaire [before the first intervention (week 1), end of the first intervention (week 5), before the second intervention (weekd 7), after the second intervention (week 11), before the third intervention (week 13), and after the third intervention (week 17)]: The Leeds Sleep Evaluation Questionnaire consists of 10 items that evaluate four domains: ease of initiating sleep, quality of sleep, ease of waking, and behavior following wakefulness. Items are rated on a 100 mm scale with a minimal score of 0 mm (represents the worst outcome) and a maximal score of 100 mm (represents the best outcome). It is an easy to implement questionnaire that has been widely used to evaluate the subjective aspect of sleep. It has been employed in a huge amount of psychological and psychopharmacological studies.
• Change from baseline in health-related quality of life, assessed using the Short Form-36 Health Survey [before the first intervention (week 1), end of the first intervention (week 5), before the second intervention (weekd 7), after the second intervention (week 11), before the third intervention (week 13), and after the third intervention (week 17)]: The Short Form-36 Health Survey is a generic survey that contains 36 items that assess the quality of life and yield eight dimensions: physical functioning, physical role, emotional role, bodily pain, general health, vitality, social functioning, and mental health. The score of each dimension ranges from 0 to 100, with higher scales implying better health status. The French version has excellent convergent and discriminant validity (100% and 97.9%, respectively) and good to excellent internal consistency (Cronbach's alpha: 0.76-0.92)
• Overall clinical improvement assessed using the Clinical Global Impression [After the first intervention (week 5), after the second intervention (week 11), after the third intervention (week 17)]: The Clinical Global Impression is a 7-point measure ranging from "very much improved" to "very much worse" since the initiation of the treatment period
• Maintenance of blinding, assessed using the blinding questionnaire [After the first intervention (week 5), after the second intervention (week 11), after the third intervention (week 17)]: Participants will complete a blinding questionnaire designed to assess the effectiveness of participant blinding and their perception of the stimulation condition received
• Difference in daily pain reporting using a Visual Analogue Scale of pain among the three stimulation conditions [Pain will be daily recorded between the first visit (week 1) and the last visit of the protocol (week 17)]: Daily pain evolution, assessed using a daily pain diary based on the VAS pain throughout the study period. Visual Analogue scale of Pain consists of rating the symptom on a 10 cm horizontal line going from 0 meaning "no pain" to 10 meaning "worst pain imaginable".

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Patients aged between 18 and 75 years,
* Patients with a definite diagnosis of fibromyalgia according to the American College of Rheumatology (ACR) 2010 criteria, set for at least one month
* Patients should be French speakers, able to understand verbal instructions, and affiliated with the national health insurance.

Exclusion Criteria:

* Patient included in another research protocol during the study period;
* Inability to comply with study procedures or follow-up requirements for geographical, social, or organizational reasons;
* Any contraindication to the use of the Exopulse Mollii Suit as specified in the device user manual;
* Any significant neurological, psychiatric, cardiovascular, musculoskeletal, or other medical condition that, in the opinion of the investigator, could interfere with study participation, outcome assessment, or participant safety, with the exception of anxiety and depression commonly associated with fibromyalgia;
* Modification of pharmacological treatment related to fibromyalgia or initiation/modification of non-pharmacological therapies within the three months preceding inclusion;
* Introduction of another therapeutic medical device during the study period;
* Pregnant women;
* Breastfeeding women;
* Individuals subject to a legal protection measure (guardianship, curatorship, or judicial protection order).

• Mattar JG, Chalah MA, Ouerchefani N, Sorel M, Le Guilloux J, Lefaucheur JP, Abi Lahoud GN, Ayache SS. The effect of the EXOPULSE Mollii Suit on pain and fibromyalgia-related symptoms-A randomized sham-controlled crossover trial. Eur J Pain. 2025 Feb;29(2):e4729. doi: 10.1002/ejp.4729. Epub 2024 Sep 18. PMID 39291602
• Riachi N, Shatila A, Diab S, Jaber H, Jawhari M, Mattar JG, Lefaucheur JP, Chalah MA, Ayache SS. The effects of EXOPULSE Mollii Suit in patients with fibromyalgia: a double-blind randomized sham-controlled trial (EXOFIB2). Pain Med. 2026 Jun 1;27(6):660-670. doi: 10.1093/pm/pnag010. PMID 41570081

• Study Protocol and Statistical Analysis Plan (PDF, 2026-08-13)