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Definition of Autonomic Nervous System Involvement in Patients With Multiple Sclerosis

Primary Purpose

Multiple Sclerosis

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
quantification of sensory and autonomic small nerve fibers by punch skin biopsy
Cardiovascular Reflexes testing
Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms
Sponsored by
Istituti Clinici Scientifici Maugeri SpA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Multiple Sclerosis focused on measuring autonomic nervous system, sensory nervous system, rehabilitation, skin biopsy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: diagnosis of relapsing-remitting and primary progressive multiple sclerosis. Exclusion Criteria: other forms of multiple sclerosis, known other neurological disorders assumption of potentially neurotoxic substances or drugs.

Sites / Locations

  • ICS Maugeri - IRCCS of Telese TermeRecruiting
  • Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico IIRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

relapsing-remitting multiple sclerosis

primary progressive multiple sclerosis

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Cardiovascular reflex test
Assessment of Cardiovascular reflex responses to physical challenges.
Sudomotor function test
Assessment of postganglionic sudomotor function through dynamic sweat test

Secondary Outcome Measures

Quantification of peripheral autonomic nerve fibers
Quantification of sweat gland innervation (fiber length /um3) and arrector pili muscle (ff/mm).
Quantification of peripheral sensory nerve fibers
Quantification of sensory nerve fibers (Intraepidermal nerve fibers (ff/mm)).

Full Information

First Posted
January 26, 2023
Last Updated
February 17, 2023
Sponsor
Istituti Clinici Scientifici Maugeri SpA
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1. Study Identification

Unique Protocol Identification Number
NCT05748015
Brief Title
Definition of Autonomic Nervous System Involvement in Patients With Multiple Sclerosis
Official Title
Definition of Autonomic Nervous System Involvement in Patients With Relapsing-remitting and Primary Progressive Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 4, 2021 (Actual)
Primary Completion Date
January 30, 2024 (Anticipated)
Study Completion Date
March 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Istituti Clinici Scientifici Maugeri SpA

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
autonomic nervous system, sensory nervous system, rehabilitation, skin biopsy

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
relapsing-remitting multiple sclerosis
Arm Type
Active Comparator
Arm Description
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.
Arm Title
primary progressive multiple sclerosis
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Diagnostic Test
Intervention Name(s)
quantification of sensory and autonomic small nerve fibers by punch skin biopsy
Intervention Description
We'll perform a punch skin biopsy of 3mm from thigh, leg and fingertip and we'll quantify peripheral sensory and autonomic nerve fibers.
Intervention Type
Diagnostic Test
Intervention Name(s)
Cardiovascular Reflexes testing
Intervention Description
Cardiovascular reflex tests including deep breathing, head-up Tilt, standing, isometric exercises, mental arithmetic and Valsalva maneuver.
Intervention Type
Other
Intervention Name(s)
Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms
Intervention Description
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 Outcome Measure Information:
Title
Cardiovascular reflex test
Description
Assessment of Cardiovascular reflex responses to physical challenges.
Time Frame
At the recruitment
Title
Sudomotor function test
Description
Assessment of postganglionic sudomotor function through dynamic sweat test
Time Frame
At the recruitment
Secondary Outcome Measure Information:
Title
Quantification of peripheral autonomic nerve fibers
Description
Quantification of sweat gland innervation (fiber length /um3) and arrector pili muscle (ff/mm).
Time Frame
At the recruitment
Title
Quantification of peripheral sensory nerve fibers
Description
Quantification of sensory nerve fibers (Intraepidermal nerve fibers (ff/mm)).
Time Frame
At the recruitment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: diagnosis of relapsing-remitting and primary progressive multiple sclerosis. Exclusion Criteria: other forms of multiple sclerosis, known other neurological disorders assumption of potentially neurotoxic substances or drugs.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vincenzo Provitera, MD
Phone
+390824909257
Email
vincenzo.provitera@icsmaugeri.it
First Name & Middle Initial & Last Name or Official Title & Degree
Giuseppe Caporaso
Phone
+390824909645
Email
giuseppe.caporaso@icsmaugeri.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vincenzo Provitera, MD
Organizational Affiliation
ICS MAUGERI - IRCCS TELESE TERME
Official's Role
Principal Investigator
Facility Information:
Facility Name
ICS Maugeri - IRCCS of Telese Terme
City
Telese Terme
State/Province
Benevento
ZIP/Postal Code
82037
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vincenzo Provitera, MD
Phone
+390824909257
Email
vincenzo.provitera@icsmaugeri.it
Facility Name
Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fiore Manganelli, MD
Phone
+0817462666
Email
fiore.manganelli@unina.it
First Name & Middle Initial & Last Name & Degree
Rosa Iodice, MD
Phone
+39081746266
Email
rosa.iodice@unina.it

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33993457
Citation
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.
Results Reference
background
PubMed Identifier
31293369
Citation
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.
Results Reference
background
PubMed Identifier
21646630
Citation
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.
Results Reference
background
PubMed Identifier
25683764
Citation
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.
Results Reference
background
PubMed Identifier
27288647
Citation
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.
Results Reference
background
PubMed Identifier
33372053
Citation
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.
Results Reference
background
PubMed Identifier
27964824
Citation
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.
Results Reference
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PubMed Identifier
11464847
Citation
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.
Results Reference
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Definition of Autonomic Nervous System Involvement in Patients With Multiple Sclerosis

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