Fibromyalgia and Small Fiber Neuropathy (FIBRO-NEP)

Fibromyalgia and Small Fiber Neuropathy : Which Prevalence and Which Relationship With Pain ?

The primary objective of this study will be to assess the proportion of fibromyalgia patients with diffuse small-fiber neuropathy (i.e. in the upper and lower limbs) and compare this proportion to patients with other chronic pains (nociplastic, nociceptive) and with healthy controls. Our analysis will be based on the demonstration of structural abnormalities of small nerve fibers by means of skin biopsy, but also of functional abnormalities using four validated tests commonly used in this field: quantitative sensory testing (QST), laser evoked potential recordings, Sudoscan and confocal corneal microscopy. It will thus be possible to verify whether or not patients with small fiber neuropathy have a particular clinical profile in terms of pain, physical activity, comorbidities or pain impact.

Study Overview

• Status: Recruiting
• Conditions: Chronic Pain Syndrome
• Intervention / Treatment: Diagnostic test: Skin punch biopsy to demonstrate small fiber neuropathy

Detailed Description

Small fiber neuropathy has been observed in a large proportion of fibromyalgia patients. However, the pathophysiological role of these neurological abnormalities in determining the pain and other symptoms of fibromyalgia, and the specificity of these abnormalities, are not well understood.

The primary objective of this study will be to assess the proportion of fibromyalgia patients with diffuse small-fiber neuropathy (i.e. in the upper and lower limbs) and compare this proportion to patients with other chronic pains (nociplastic, nociceptive) and with healthy controls. Our analysis will be based on the demonstration of structural abnormalities of small nerve fibers by means of skin biopsy, but also of functional abnormalities using four validated tests commonly used in this field: quantitative sensory testing (QST), laser evoked potential recordings, Sudoscan and confocal corneal microscopy. It will thus be possible to verify whether or not patients with small fiber neuropathy have a particular clinical profile in terms of pain, physical activity, comorbidities or pain impact.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Nadine ATTAL, MD PhD; Phone Number: 0033149095931; Email: nadine.attal@aphp.fr
• Study Contact Backup: Name: Didier BOUHASSIRA, MD PHD; Phone Number: 0033149094556; Email: didier.bouhassira@inserm.fr

Study Locations

• France
  • Boulogne-Billancourt, France, 92100
    • Recruiting
    • Inserm U987
    • Principal Investigator: Serge PERROT
    • Contact: Nadine ATTAL; Phone Number: 0033149095931; Email: nadine.attal@aphp.fr
    • Sub-Investigator: Didier BOUHASSIRA
  • Paris, France, 75014
    • Recruiting
    • Centre d'Evaluation et de Traitement de la douleur
    • Sub-Investigator: Anne-Priscille TROUVIN
    • Contact: Serge PERROT; Phone Number: 0033158414141; Email: serge.perrot@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with fibromyalgia, other chronic pains (nociplastic or nociceptive) and healthy subjects

Description

Inclusion Criteria:

• patients over 18 years of age with no age limit -
• having given their signed consent to take part in the study
• affiliated to the French social security system
• able to be followed for the entire duration of the study
• reading and understanding French
• accepting the principle of the study and able to comply with its conditions
• suffering from chronic pain for at least six months of at least moderate intensity (≥ 4/10)
• fibromyalgia detected by the FiRST questionnare and defined by the revised diagnostic criteria of the WHO or chronic nociceptive or nociplastic pain without associated fibromyalgia.
• chronic pain for at least 6 months of at least moderate intensity (≥ 4/10)
• untreated or with stable analgesic treatment for at least 2 weeks prior to inclusion- normal neurological examination at inclusion

Exclusion Criteria:

• litigation or compensation-seeking
• cancer for less than 2 years
• known cause of small-fiber neuropathy such as diabetes, systemic disease, hypothyroidism, alcohol, renal failure, genetic disease
• clinical or EMG neuropathy
• peripheral or central nervous system pathology with or without associated neuropathic pain
• uncontrolled chronic pathology such as : morbid obesity, sleep apnea, uncontrolled hypertension, etc. - psychosis, previous suicide attempt
• drug or psychoactive substance abuse
• cognitive or psychological disorders incompatible with compliance with and/or understanding of the protocol
• participation in another biomedical research protocol.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with fibromyalgia; Patients with fibromyalgia based on ACR criteria	Diagnostic test: Skin punch biopsy to demonstrate small fiber neuropathy; Skin punch biopsy to assess intrapidermal nerve fiber density; Other Names: Other diagnostic tests will include laser evoked potentiels, quantitative sensory testing, sudoscan, and confocal corneal microscopu
Patients with other chronic pain (paired for the other groups); Patients with chronic pain other than fibromyalgia and neuropathic pain, eg nociplastic pains or nociceptive pains	Diagnostic test: Skin punch biopsy to demonstrate small fiber neuropathy; Skin punch biopsy to assess intrapidermal nerve fiber density; Other Names: Other diagnostic tests will include laser evoked potentiels, quantitative sensory testing, sudoscan, and confocal corneal microscopu
Paired healthy subjects; Healthy subjects paired for gender and age	Diagnostic test: Skin punch biopsy to demonstrate small fiber neuropathy; Skin punch biopsy to assess intrapidermal nerve fiber density; Other Names: Other diagnostic tests will include laser evoked potentiels, quantitative sensory testing, sudoscan, and confocal corneal microscopu

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of small fiber neuropathy or pathology as assessed with skin punch biopsy in patients with fibromyalgia as compared to patients with other chronic pains and healthy subjects	intraepidermal nerve fiber density	Baseline and at 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between intraepidermal nerve fiber density and pain or other patient reported outcome measures (quality of life, distress, disability...)	Correlation statistics (Spearman Rho)	Baseline and at 6 months
Investigate the potential specificity of the results obtained by comparing them with pain patients without fibromyalgia or nerve damage (patients with any nociceptive or nociplastic pain without fibromyalgia) matched for age and gender	Direct group comparisons	Baseline and at 6 months
Monitor the evolution of abnormalities obtained over time (6 months) and correlate them with the evolution of pain and associated symptoms.	Comparison of intraepidermal nerve fiber density and other diagnostic measures between baseline and 6 months	6 months
Determine the sensitivity and diagnostic value of corneal confocal microscopy and laser evoked potentials as compared with skin punch biopsy for exploring nociceptive fibers	Sensitivity and specificy of these tests compared to skin punch biopsy	Baseline and at 6 months
Determine the diagnostic value of the sudoscan and quantified sensory tests compared with other tests for exploring nociceptive fibers in these patients	Sensitivity and specificy of sudoscan and quantitative sensory testing compared to skin punch biopsy	Baseline and at 6 months

Collaborators and Investigators

• Sponsor: Hospital Ambroise Paré Paris
• Investigators: Principal Investigator: Nadine ATTAL, MD PhD, APHP

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2022
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: July 24, 2024
• First Submitted That Met QC Criteria: July 24, 2024
• First Posted (Actual): July 30, 2024

Study Record Updates

• Last Update Posted (Estimated): September 10, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Chronic Pain; Fibromyalgia; Small Fiber Neuropathy
• Other Study ID Numbers: 2020-A03400-39

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No