Definition of Autonomic Nervous System Involvement in Patients With Multiple Sclerosis

Sponsor

Istituti Clinici Scientifici Maugeri SpA (Other)

Overall Status

Recruiting

CT.gov ID

NCT05748015

Collaborator

(none)

Enrollment

Locations

Arms

36.9

Anticipated Duration (Months)

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	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	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Definition of Autonomic Nervous System Involvement in Patients With Relapsing-remitting and Primary Progressive Multiple Sclerosis

Actual Study Start Date :

Mar 4, 2021

Anticipated Primary Completion Date :

Jan 30, 2024

Anticipated Study Completion Date :

Mar 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: relapsing-remitting multiple sclerosis 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 We'll perform a punch skin biopsy of 3mm from thigh, leg and fingertip and we'll quantify peripheral sensory and autonomic nerve fibers. Diagnostic Test: Cardiovascular Reflexes testing Cardiovascular reflex tests including deep breathing, head-up Tilt, standing, isometric exercises, mental arithmetic and Valsalva maneuver. Other: Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms 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
Active Comparator: primary progressive multiple sclerosis 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 We'll perform a punch skin biopsy of 3mm from thigh, leg and fingertip and we'll quantify peripheral sensory and autonomic nerve fibers. Diagnostic Test: Cardiovascular Reflexes testing Cardiovascular reflex tests including deep breathing, head-up Tilt, standing, isometric exercises, mental arithmetic and Valsalva maneuver. Other: Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms 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

Arm

Intervention/Treatment

Active Comparator: relapsing-remitting multiple sclerosis

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

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

Diagnostic Test: Cardiovascular Reflexes testing

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

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

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

Active Comparator: primary progressive multiple sclerosis

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

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

Diagnostic Test: Cardiovascular Reflexes testing

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

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

Outcome Measures

Primary Outcome Measures

Cardiovascular reflex test [At the recruitment]
Assessment of Cardiovascular reflex responses to physical challenges.
Sudomotor function test [At the recruitment]
Assessment of postganglionic sudomotor function through dynamic sweat test

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ICS Maugeri - IRCCS of Telese Terme	Telese Terme	Benevento	Italy	82037
2	Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II	Napoli		Italy	80131