Photobiomodulation for Chronic Pain and Fatigue in Hypermobile Ehlers-Danlos Syndrome (PBM-SEDh-01) (PBM-SEDh-01)

Effect of MLS® Class IV Laser Photobiomodulation on Chronic Pain and Fatigue in Hypermobile Ehlers-Danlos Syndrome: A Prospective Observational Pilot Study in Private Medical Practice

This study evaluates the effect of photobiomodulation (PBM) therapy using a MLS® class IV laser on chronic pain and fatigue in patients with hypermobile Ehlers-Danlos Syndrome (hEDS). hEDS is a hereditary connective tissue disorder characterized by joint hypermobility, chronic pain, and debilitating fatigue, for which therapeutic options remain limited.

Participants will receive 10 PBM sessions over 5 weeks (2 sessions per week), using red and near-infrared light (808 nm continuous + 905 nm pulsed) applied to painful areas identified at baseline. Pain (Visual Analogue Scale), multidimensional fatigue (MFI-20), and quality of life (EQ-5D-5L) will be assessed at baseline (T0), end of treatment (week 5), and follow-up (week 10).

This is a pilot observational study - the first to document the effect of MLS® laser PBM in hEDS. No additional procedures beyond routine care are required.

Study Overview

• Status: Recruiting
• Conditions: Chronic Pain; Fatigue Syndrome, Chronic; Ehlers-Danlos Syndrome, Hypermobile

Detailed Description

Background: Hypermobile Ehlers-Danlos Syndrome (hEDS) is the most common form of EDS (80-90% of cases), diagnosed according to the 2017 International Consortium criteria. Chronic pain and fatigue are the two most disabling symptoms. No randomized controlled trial has evaluated the effect of MLS® class IV laser photobiomodulation in hEDS to date.

Intervention: Photobiomodulation using ASAlaser M-Hi device (MLS® technology: synchronized 808nm continuous + 905nm pulsed emissions, CE MDR class IV). Progressive fluence: 4 J/cm² (sessions 1-2), 6 J/cm² (sessions 3-6), 8 J/cm² (sessions 7-10). Maximum 3-4 zones per session. Treatment areas individualized based on pain mapping at baseline.

Design: Single-center prospective observational pilot study in private practice. No randomization, no control group, no modification of ongoing treatment.

Statistical analysis: Wilcoxon signed-rank tests (paired, non-parametric), descriptive statistics. Exploratory pilot - no formal power calculation. Target sample size: 20-25 patients.

• Study Type: Observational
• Enrollment (Estimated): 25

Contacts and Locations

• Study Contact: Name: Lilian Lessedjina, M.D.; Phone Number: +337-82-83-40-83; Email: dr.llessedjina@gmail.com

Study Locations

• France
  • Île-de-France Region
    • Boulogne-Billancourt, Île-de-France Region, France, 92100
      • Recruiting
      • Centre Médical ISM
      • Contact: Lilian Lessedjina, M.D.; Phone Number: +337-82-83-40-83; Email: dr.llessedjina@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with confirmed hypermobile Ehlers-Danlos Syndrome (hEDS), diagnosed according to the 2017 International Consortium criteria, presenting with chronic pain (≥ 3 months, VAS ≥ 4/10) and/or fatigue, followed in private outpatient practice at Centre Médical ISM, Boulogne-Billancourt, France. Patients are recruited consecutively among those already receiving photobiomodulation therapy as part of their routine care. No healthy volunteers are included.

Description

Inclusion Criteria:

• Age ≥ 18 years
• Confirmed diagnosis of hypermobile Ehlers-Danlos Syndrome (hEDS) according to 2017 International Consortium criteria
• Chronic pain ≥ 3 months, average VAS score ≥ 4/10 over the preceding week
• Stable analgesic treatment for ≥ 4 weeks (if any)
• Follow-up at Centre Médical ISM, Boulogne-Billancourt
• Informed and non-opposition signed

Exclusion Criteria:

• Suspicious or malignant skin lesion on areas to be treated
• Non-modifiable photosensitizing treatment
• Pregnancy or breastfeeding
• Photosensitive epilepsy
• Acute articular inflammatory flare at inclusion date
• Analgesic treatment modification within 4 weeks prior to inclusion
• Simultaneous participation in another research protocol

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in chronic pain intensity	Change in pain intensity measured by the Visual Analogue Scale (VAS, 0-10), representing average pain over the preceding week. A decrease of ≥ 1.5 points is considered clinically meaningful.	Baseline (T0) to Week 5 (end of PBM treatment cycle)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in multidimensional fatigue	Change in fatigue assessed by the Multidimensional Fatigue Inventory (MFI-20), comprising 20 items across 5 subscales: General Fatigue, Physical Fatigue, Reduced Activity, Reduced Motivation, and Mental Fatigue. Total score ranges from 20 to 100.	Baseline (T0), Week 5 (T5), and Week 10 (T10)
Change in health-related quality of life	Change in quality of life assessed by the EQ-5D-5L questionnaire (5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and the EQ Visual Analogue Scale (EQ-VAS, 0-100).	Baseline (T0), Week 5 (T5), and Week 10 (T10)
Durability of pain relief	Change in pain intensity assessed by the Visual Analogue Scale (VAS, 0-10, where 0 = no pain and 10 = worst pain imaginable; lower scores indicate less pain), between end of treatment (Week 5) and follow-up (Week 10), to assess persistence of the analgesic effect after PBM cessation	Week 5 to Week 10 (5 weeks post-treatment follow-up)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability of PBM therapy	Frequency and nature of local adverse events (redness, discomfort, transient pain aggravation) recorded at each session by the investigator.	Each session, from Week 1 to Week 5 (sessions 1 to 10)

Collaborators and Investigators

• Sponsor: Centre Medical ISM (Integrative Systemic Medicine)

Publications and helpful links

General Publications

• Robijns J, Nair RG, Lodewijckx J, Arany P, Barasch A, Bjordal JM, Bossi P, Chilles A, Corby PM, Epstein JB, Elad S, Fekrazad R, Fregnani ER, Genot MT, Ibarra AMC, Hamblin MR, Heiskanen V, Hu K, Klastersky J, Lalla R, Latifian S, Maiya A, Mebis J, Migliorati CA, Milstein DMJ, Murphy B, Raber-Durlacher JE, Roseboom HJ, Sonis S, Treister N, Zadik Y, Bensadoun RJ. Photobiomodulation therapy in management of cancer therapy-induced side effects: WALT position paper 2022. Front Oncol. 2022 Aug 30;12:927685. doi: 10.3389/fonc.2022.927685. eCollection 2022.
• Castori M, Camerota F, Celletti C, Danese C, Santilli V, Saraceni VM, Grammatico P. Natural history and manifestations of the hypermobility type Ehlers-Danlos syndrome: a pilot study on 21 patients. Am J Med Genet A. 2010 Mar;152A(3):556-64. doi: 10.1002/ajmg.a.33231.
• Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, Bloom L, Bowen JM, Brady AF, Burrows NP, Castori M, Cohen H, Colombi M, Demirdas S, De Backer J, De Paepe A, Fournel-Gigleux S, Frank M, Ghali N, Giunta C, Grahame R, Hakim A, Jeunemaitre X, Johnson D, Juul-Kristensen B, Kapferer-Seebacher I, Kazkaz H, Kosho T, Lavallee ME, Levy H, Mendoza-Londono R, Pepin M, Pope FM, Reinstein E, Robert L, Rohrbach M, Sanders L, Sobey GJ, Van Damme T, Vandersteen A, van Mourik C, Voermans N, Wheeldon N, Zschocke J, Tinkle B. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):8-26. doi: 10.1002/ajmg.c.31552.

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2026
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: June 4, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: photobiomodulation; laser therapy; MLS laser; Ehlers-Danlos syndrome; chronic pain; fatigue; quality of life; observational study; pilot study
• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Pain; Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Muscular Diseases; Pathologic Processes; Encephalomyelitis; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Genetic Diseases, Inborn; Connective Tissue Diseases; Hematologic Diseases; Skin Diseases; Congenital Abnormalities; Hemostatic Disorders; Hemorrhagic Disorders; Skin Diseases, Genetic; Skin Abnormalities; Collagen Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Hemic and Lymphatic Diseases; Fatigue Syndrome, Chronic; Chronic Pain; Fatigue; Ehlers-Danlos Syndrome
• Other Study ID Numbers: PBM-SEDh-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No