Longitudinal Assessment of Autonomic and Sensory Nervous System in ALS

NCT ID: NCT05747937

Last Updated: 2025-01-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-15

Study Completion Date

2025-12-30

Brief Summary

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The goal of this interventional non-pharmacological study is to evaluate, using a multimodal approach, the progression of autonomic and sensory involvement in in amyotrophic lateral sclerosis (ALS) patients enrolled within 18 months from motor onset and its relationship with the progression of overall clinical disability.

The main questions it aims to answer are:

* Is autonomic dysfunction at diagnosis associated with disease progression and survival in patients with Amyotrophic Lateral Sclerosis ?
* Can we identify in the skin biomarkers to be used as reliable measures of disease progression and to apply in future clinical trials for patient stratification and to assess response to drug treatment ? Participants at time 0 will receive a full clinical and instrumental examination and a blood sample testing to check inclusion and exclusion criteria, genetic screening for the most common genes associated with ALS (SOD1, FUS, TARDBP and c9orf72), questionnaires about clinical characteristics, quality of life, pain and a multidomain battery of neuropsychological tests, multimodal assessment of the autonomic nervous system including skin biopsy for morphological study. At follow-up we'll perform clinical scales and skin biopsy.

Researchers will compare results from ALS patients with data obtained from a population of age and sex matched healthy subjects.

Detailed Description

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Conditions

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Amyotrophic Lateral Sclerosis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

There are not masking participants

Study Groups

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Amyotrophic Lateral Sclerosis patients

Amyotrophic Lateral Sclerosis (ALS) patients within 18 months from symptoms onset will be recruited

Group Type EXPERIMENTAL

Skin biopsy

Intervention Type DIAGNOSTIC_TEST

A punch skin biopsy of 3mm will be used to analyze cutaneous innervation

Cardiovascular Reflexes testing

Intervention Type DIAGNOSTIC_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 symptoms

Intervention Type DIAGNOSTIC_TEST

We'll characterize patients' symptoms through the administration of clinical scales such as: SCOPA-AUT autonomic symptoms scale; Brief Pain Inventory questionnaire

Dinamic Sweat Test

Intervention Type DIAGNOSTIC_TEST

Test for the functional assessment of postganglionic sudomotor pathway

Healthy controls

A population of healthy controls matched for sex and age will be enrolled

Group Type ACTIVE_COMPARATOR

Skin biopsy

Intervention Type DIAGNOSTIC_TEST

A punch skin biopsy of 3mm will be used to analyze cutaneous innervation

Cardiovascular Reflexes testing

Intervention Type DIAGNOSTIC_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 symptoms

Intervention Type DIAGNOSTIC_TEST

We'll characterize patients' symptoms through the administration of clinical scales such as: SCOPA-AUT autonomic symptoms scale; Brief Pain Inventory questionnaire

Dinamic Sweat Test

Intervention Type DIAGNOSTIC_TEST

Test for the functional assessment of postganglionic sudomotor pathway

Interventions

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Skin biopsy

A punch skin biopsy of 3mm will be used to analyze cutaneous innervation

Intervention Type DIAGNOSTIC_TEST

Cardiovascular Reflexes testing

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

Intervention Type DIAGNOSTIC_TEST

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: SCOPA-AUT autonomic symptoms scale; Brief Pain Inventory questionnaire

Intervention Type DIAGNOSTIC_TEST

Dinamic Sweat Test

Test for the functional assessment of postganglionic sudomotor pathway

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* ALS patients will be recruited within 18 months from the motor symptoms onset

Exclusion Criteria

* glucose intolerance or conditions potentially affecting the peripheral nervous system
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Istituti Clinici Scientifici Maugeri SpA

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Maria Nolano, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Istituti Clinici Scientifici Maugeri SpA

Locations

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ICS Maugeri - IRCCS of Telese Terme

Telese Terme, Benevento, Italy

Site Status RECRUITING

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

Napoli, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Maria Nolano, MD, PhD

Role: CONTACT

+390824909257

Giuseppe Caporaso

Role: CONTACT

+390824909645

Facility Contacts

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Vincenzo Provitera, MD

Role: primary

+390824909257

Raffaele Dubbioso, MD

Role: primary

0817464587

References

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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.

Reference Type BACKGROUND
PMID: 33993457 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31293369 (View on PubMed)

Sassone J, Taiana M, Lombardi R, Porretta-Serapiglia C, Freschi M, Bonanno S, Marcuzzo S, Caravello F, Bendotti C, Lauria G. ALS mouse model SOD1G93A displays early pathology of sensory small fibers associated to accumulation of a neurotoxic splice variant of peripherin. Hum Mol Genet. 2016 Apr 15;25(8):1588-99. doi: 10.1093/hmg/ddw035. Epub 2016 Feb 9.

Reference Type BACKGROUND
PMID: 26908600 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21646630 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25683764 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27288647 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33372053 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27964824 (View on PubMed)

Fasolino A, Di Stefano G, Leone C, Galosi E, Gioia C, Lucchino B, Terracciano A, Di Franco M, Cruccu G, Truini A. Small-fibre pathology has no impact on somatosensory system function in patients with fibromyalgia. Pain. 2020 Oct;161(10):2385-2393. doi: 10.1097/j.pain.0000000000001920.

Reference Type BACKGROUND
PMID: 32897040 (View on PubMed)

Finnerup NB, Haroutounian S, Kamerman P, Baron R, Bennett DLH, Bouhassira D, Cruccu G, Freeman R, Hansson P, Nurmikko T, Raja SN, Rice ASC, Serra J, Smith BH, Treede RD, Jensen TS. Neuropathic pain: an updated grading system for research and clinical practice. Pain. 2016 Aug;157(8):1599-1606. doi: 10.1097/j.pain.0000000000000492.

Reference Type BACKGROUND
PMID: 27115670 (View on PubMed)

Damon-Perriere N, Foubert-Samier A, De Cock VC, Gerdelat-Mas A, Debs R, Pavy-Le Traon A, Senard JM, Rascol O, Tison F, Meissner WG. Assessment of the Scopa-Aut questionnaire in multiple system atrophy: relation to UMSARS scores and progression over time. Parkinsonism Relat Disord. 2012 Jun;18(5):612-5. doi: 10.1016/j.parkreldis.2011.12.009. Epub 2012 Jan 9.

Reference Type BACKGROUND
PMID: 22236582 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11464847 (View on PubMed)

Other Identifiers

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SBLAB/SLA20

Identifier Type: -

Identifier Source: org_study_id

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