Definition of Autonomic Nervous System Involvement in Patients With Multiple Sclerosis

NCT05748015 | Recruiting

• 1 other identifier: SBLAB/SM20
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this interventional non-pharmacological study is to evaluate the involvement of the autonomic nervous system in patients with relapsing-remitting and primary progressive multiple sclerosis. The main questions it aims to answer are:

• Is it possible to define the characteristics of dysautonomia to improve treatment on patients with multiple sclerosis through the management of conditions such as orthostatic hypotension or thermoregulation disorders that inevitably condition the patient's life and the response to rehabilitation ?
• Does the severity of the functional alterations correlate with impairment of small somatic and autonomic cutaneous nerve fibers in patients with multiple sclerosis ?
• How much the involvement of the autonomic nervous system affects the clinical history and progression of the disease ?
• Do different clinical variants of multiple sclerosis manifest with different patterns of involvement of the sensory-autonomic nervous system ? Participants will be hospitalized in Maugeri Clinical Institute of Telese Terme for a rehabilitation treatment. Patients will perform a sensory and autonomic functional study and a morphological analysis of cutaneous nerves through skin biopsy. Researchers will compare results between the two groups (relapsing-remitting and primary progressive) and between patients and data from control subjects.

Conditions

Multiple Sclerosis

Keywords

autonomic nervous system; sensory nervous system; rehabilitation; skin biopsy

Outcome Measures

Primary Outcomes (2)

• Cardiovascular reflex test

  Assessment of Cardiovascular reflex responses to physical challenges.

  At the recruitment

• Sudomotor function test

  Assessment of postganglionic sudomotor function through dynamic sweat test

  At the recruitment

Secondary Outcomes (2)

• Quantification of peripheral autonomic nerve fibers

  At the recruitment

• Quantification of peripheral sensory nerve fibers

  At the recruitment

Study Arms (2)

relapsing-remitting multiple sclerosis

ACTIVE COMPARATOR

Patients with relapsing-remitting multiple sclerosis will be hospitalized in Maugeri Clinical Institute of Telese Terme for a rehabilitation treatment and will perform a functional and morphological study of sensory and autonomic nervous system, evaluation of peripheral sensory and autonomic nerve fibers performed by skin biopsy.

Diagnostic Test: quantification of sensory and autonomic small nerve fibers by punch skin biopsy; Diagnostic Test: Cardiovascular Reflexes testing; Other: Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms

primary progressive multiple sclerosis

ACTIVE COMPARATOR

Patients with primary progressive multiple sclerosis will be hospitalized in Maugeri Clinical Institute of Telese Terme for a rehabilitation treatment and will perform a functional and morphological study of sensory and autonomic nervous system, evaluation of peripheral sensory and autonomic nerve fibers performed by skin biopsy.

Diagnostic Test: quantification of sensory and autonomic small nerve fibers by punch skin biopsy; Diagnostic Test: Cardiovascular Reflexes testing; Other: Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms

Interventions

quantification of sensory and autonomic small nerve fibers by punch skin biopsy DIAGNOSTIC_TEST

We'll perform a punch skin biopsy of 3mm from thigh, leg and fingertip and we'll quantify peripheral sensory and autonomic nerve fibers.

primary progressive multiple sclerosis; relapsing-remitting multiple sclerosis

Cardiovascular Reflexes testing DIAGNOSTIC_TEST

Cardiovascular reflex tests including deep breathing, head-up Tilt, standing, isometric exercises, mental arithmetic and Valsalva maneuver.

primary progressive multiple sclerosis; relapsing-remitting multiple sclerosis

Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms OTHER

We'll characterize patients' symptoms through the administration of clinical scales such as: COMPASS 31 autonomic symptoms scale; Small Fiber Neuropathy Symptom Inventory Questionnaire (SFN-SIQ), the Pain Detect Questionnaire and the Total neuropathy score

primary progressive multiple sclerosis; relapsing-remitting multiple sclerosis

Eligibility Criteria

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

You may qualify if:

• diagnosis of relapsing-remitting and primary progressive multiple sclerosis.

You may not qualify if:

• other forms of multiple sclerosis,
• known other neurological disorders
• assumption of potentially neurotoxic substances or drugs.

Sponsors & Collaborators

• Istituti Clinici Scientifici Maugeri SpA: lead

Study Sites (2)

ICS Maugeri - IRCCS of Telese Terme

Telese Terme, Benevento, 82037, Italy

RECRUITING

Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II

Naples, 80131, Italy

RECRUITING

Related Publications (8)

• Mahoney CJ, Ahmed RM, Huynh W, Tu S, Rohrer JD, Bedlack RS, Hardiman O, Kiernan MC. Pathophysiology and Treatment of Non-motor Dysfunction in Amyotrophic Lateral Sclerosis. CNS Drugs. 2021 May;35(5):483-505. doi: 10.1007/s40263-021-00820-1. Epub 2021 May 15.

  PMID: 33993457 BACKGROUND

• Gentile F, Scarlino S, Falzone YM, Lunetta C, Tremolizzo L, Quattrini A, Riva N. The Peripheral Nervous System in Amyotrophic Lateral Sclerosis: Opportunities for Translational Research. Front Neurosci. 2019 Jun 25;13:601. doi: 10.3389/fnins.2019.00601. eCollection 2019.

  PMID: 31293369 BACKGROUND

• Weis J, Katona I, Muller-Newen G, Sommer C, Necula G, Hendrich C, Ludolph AC, Sperfeld AD. Small-fiber neuropathy in patients with ALS. Neurology. 2011 Jun 7;76(23):2024-9. doi: 10.1212/WNL.0b013e31821e553a.

  PMID: 21646630 BACKGROUND

• Truini A, Biasiotta A, Onesti E, Di Stefano G, Ceccanti M, La Cesa S, Pepe A, Giordano C, Cruccu G, Inghilleri M. Small-fibre neuropathy related to bulbar and spinal-onset in patients with ALS. J Neurol. 2015;262(4):1014-8. doi: 10.1007/s00415-015-7672-0. Epub 2015 Feb 17.

  PMID: 25683764 BACKGROUND

• Nolano M, Provitera V, Manganelli F, Iodice R, Caporaso G, Stancanelli A, Marinou K, Lanzillo B, Santoro L, Mora G. Non-motor involvement in amyotrophic lateral sclerosis: new insight from nerve and vessel analysis in skin biopsy. Neuropathol Appl Neurobiol. 2017 Feb;43(2):119-132. doi: 10.1111/nan.12332. Epub 2016 Jul 7.

  PMID: 27288647 BACKGROUND

• deCarvalho M, Gromicho M, Andersen P, Grosskreutz J, Kuzma-Kozakiewicz M, Petri S, Uysal H, Pinto S. Peripheral neuropathy in ALS: phenotype association. J Neurol Neurosurg Psychiatry. 2021 Oct;92(10):1133-1134. doi: 10.1136/jnnp-2020-325164. Epub 2020 Dec 28. No abstract available.

  PMID: 33372053 BACKGROUND

• Chio A, Mora G, Lauria G. Pain in amyotrophic lateral sclerosis. Lancet Neurol. 2017 Feb;16(2):144-157. doi: 10.1016/S1474-4422(16)30358-1. Epub 2016 Dec 8.

  PMID: 27964824 BACKGROUND

• Brooks BR, Miller RG, Swash M, Munsat TL; World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9. doi: 10.1080/146608200300079536. No abstract available.

  PMID: 11464847 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Vincenzo Provitera, MD

  ICS MAUGERI - IRCCS TELESE TERME

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vincenzo Provitera, MD

CONTACT

+390824909257; vincenzo.provitera@icsmaugeri.it

Giuseppe Caporaso

CONTACT

+390824909645; giuseppe.caporaso@icsmaugeri.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2023
• First Posted: February 28, 2023
• Study Start: March 4, 2021
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): May 30, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)