Multiple SclerosisNCT05748015
Definition of Autonomic Nervous System Involvement in Patients With Multiple Sclerosis
A study testing quantification of sensory and autonomic small nerve fibers by punch skin biopsy, Cardiovascular Reflexes testing and Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms in people with Multiple Sclerosis, run by Istituti Clinici Scientifici Maugeri SpA at 2 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- quantification of sensory and autonomic small nerve fibers by punch skin biopsy, Cardiovascular Reflexes testing and Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesItaly
- Study dates
- 4 Mar 2021to 30 May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- diagnosis of relapsing-remitting and primary progressive multiple sclerosis.
Who cannot join
- other forms of multiple sclerosis,
- known other neurological disorders
- assumption of potentially neurotoxic substances or drugs.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy2 sites, 2 recruiting
- Recruiting
Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II
Naples, 80131
Fiore Manganelli, MD, +0817462666, fiore.manganelli@unina.it
Rosa Iodice, MD, +39081746266, rosa.iodice@unina.it
- Recruiting
ICS Maugeri - IRCCS of Telese Terme
Telese Terme, Benevento, 82037
Vincenzo Provitera, MD, +390824909257, vincenzo.provitera@icsmaugeri.it
About this study
Official title: Definition of Autonomic Nervous System Involvement in Patients With Relapsing-remitting and Primary Progressive Multiple Sclerosis
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:
Read more
- 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
- Being tested
- 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
- Keywords
- autonomic nervous system, sensory nervous system, rehabilitation, skin biopsy
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
quantification of sensory and autonomic small nerve fibers by punch skin biopsyDiagnostic 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.
Cardiovascular Reflexes testingDiagnostic test
Cardiovascular reflex tests including deep breathing, head-up Tilt, standing, isometric exercises, mental arithmetic and Valsalva maneuver.
Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptomsOther
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiovascular reflex test
Assessment of Cardiovascular reflex responses to physical challenges.
Measured: At the recruitment
Sudomotor function test
Assessment of postganglionic sudomotor function through dynamic sweat test
Measured: At the recruitment
Secondary outcomes (2)
Quantification of peripheral autonomic nerve fibers
Quantification of sweat gland innervation (fiber length /um3) and arrector pili muscle (ff/mm).
Measured: At the recruitment
Quantification of peripheral sensory nerve fibers
Quantification of sensory nerve fibers (Intraepidermal nerve fibers (ff/mm)).
Measured: At the recruitment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2023
- Study start4 Mar 2021
- Primary completion30 Nov 2026 (estimated)
- Study completion30 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Istituti Clinici Scientifici Maugeri SpAThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituti Clinici Scientifici Maugeri SpA
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vincenzo Provitera, MD, Principal investigator, ICS MAUGERI - IRCCS TELESE TERME
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05748015
- Sponsor's protocol ID
- SBLAB/SM20
- Status last verified
- Apr 2026
- First submitted
- 26 Jan 2023
- Last updated
- 17 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33993457Gentile 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.
PubMed 31293369Weis 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.
PubMed 21646630Truini 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.
PubMed 25683764Nolano 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.
PubMed 27288647deCarvalho 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.
PubMed 33372053Chio 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.
PubMed 27964824Brooks 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.
PubMed 11464847
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Definition of Autonomic Nervous System Involvement in Patients With Relapsing-remitting and Primary Progressive Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT05748015
- Acronym / sponsor ID
- SBLAB/SM20
- Conditions
- Multiple Sclerosis
- Keywords
- autonomic nervous system, sensory nervous system, rehabilitation, skin biopsy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Istituti Clinici Scientifici Maugeri SpAUniversity, hospital or other
- Study start
- 4 Mar 2021 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 30 May 2027 (estimated)
- First posted
- 28 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| relapsing-remitting multiple sclerosis | Active comparator | 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 symptomsPatients 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. |
| primary progressive multiple sclerosis | Active comparator | 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 symptomsPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- diagnosis of relapsing-remitting and primary progressive multiple sclerosis.
Key exclusion criteria (3 listed)
- other forms of multiple sclerosis,
- known other neurological disorders
- assumption of potentially neurotoxic substances or drugs.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| quantification of sensory and autonomic small nerve fibers by punch skin biopsyWe'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 | primary progressive multiple sclerosis, relapsing-remitting multiple sclerosis |
| Cardiovascular Reflexes testingCardiovascular reflex tests including deep breathing, head-up Tilt, standing, isometric exercises, mental arithmetic and Valsalva maneuver. | Diagnostic test | primary progressive multiple sclerosis, relapsing-remitting multiple sclerosis |
| Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptomsWe'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 | Other | primary progressive multiple sclerosis, relapsing-remitting multiple sclerosis |
Primary outcome
Cardiovascular reflex test
Time frame: At the recruitment
Assessment of Cardiovascular reflex responses to physical challenges.
Sudomotor function test
Time frame: At the recruitment
Assessment of postganglionic sudomotor function through dynamic sweat test
2 secondary outcomes
Quantification of peripheral autonomic nerve fibers
Time frame: At the recruitment
Quantification of peripheral sensory nerve fibers
Time frame: At the recruitment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2026.
- Background: PubMed 33993457Mahoney 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.
- Background: PubMed 31293369Gentile 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.
- Background: PubMed 21646630Weis 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.
- Background: PubMed 25683764Truini 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.
- Background: PubMed 27288647Nolano 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.
- Background: PubMed 33372053deCarvalho 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.
- Background: PubMed 27964824Chio 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.
- Background: PubMed 11464847Brooks 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Vincenzo Provitera, MD principal investigator
ICS MAUGERI - IRCCS TELESE TERME
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing quantification of sensory and autonomic small nerve fibers by punch skin biopsy, Cardiovascular Reflexes testing and Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms in people with Multiple Sclerosis, run by Istituti Clinici Scientifici Maugeri SpA at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vincenzo Provitera, MD (+390824909257, vincenzo.provitera@icsmaugeri.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiovascular reflex test (time frame: At the recruitment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05748015, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026.