Longitudinal Assessment of Autonomic and Sensory Nervous System in ALS

NCT05747937 | Recruiting

• 1 other identifier: SBLAB/SLA20
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Autonomic nervous system; skin biopsy; biomarkers; cutaneous sensory an autonomic innervation

Outcome Measures

Primary Outcomes (4)

• Sensory peripheral innervation (IENF)

  Quantification Intraepidermal Nerve Fibers (IENF ff/mm) in skin biopsy from fingertip, thigh and leg.

  At recruitment

• Autonomic peripheral innervation

  Quantification of nerves in sweat gland (fiber lenght/um3) in skin biopsy from fingertip, thigh and leg. Quantification of nerves in arrector pili muscle (ff/mm) in skin biopsy from thigh and leg.

  At recruitment

• Autonomic peripheral innervation

  Quantification sweat gland (fiber lenght/um3) and arrector pili muscle (ff/mm) innervation in skin biopsy from thigh.

  At follow-up, an average of 6 months

• Sensory peripheral innervation (IENF)

  Quantification Intraepidermal Nerve Fibers (IENF ff/mm) in skin biopsy from thigh.

  At follow-up, an average of 6 months

Secondary Outcomes (4)

• Sensory and autonomic symptoms evaluated by clinical scales

  At the recruitment

• Sensory and autonomic symptoms evaluated by clinical scales

  At follow-up, an average of 6 months

• Assessment of Cardiovascular function

  baseline

• Sudomotor function

  baseline

Study Arms (2)

Amyotrophic Lateral Sclerosis patients

EXPERIMENTAL

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

Diagnostic Test: Skin biopsy; Diagnostic Test: Cardiovascular Reflexes testing; Diagnostic Test: Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms; Diagnostic Test: Dinamic Sweat Test

Healthy controls

ACTIVE COMPARATOR

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

Diagnostic Test: Skin biopsy; Diagnostic Test: Cardiovascular Reflexes testing; Diagnostic Test: Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms; Diagnostic Test: Dinamic Sweat Test

Interventions

Skin biopsy DIAGNOSTIC_TEST

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

Amyotrophic Lateral Sclerosis patients; Healthy controls

Cardiovascular Reflexes testing DIAGNOSTIC_TEST

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

Amyotrophic Lateral Sclerosis patients; Healthy controls

Dinamic Sweat Test DIAGNOSTIC_TEST

Test for the functional assessment of postganglionic sudomotor pathway

Amyotrophic Lateral Sclerosis patients; Healthy controls

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

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

Amyotrophic Lateral Sclerosis patients; Healthy controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• glucose intolerance or conditions potentially affecting the peripheral nervous system

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 (12)

• 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

• 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.

  PMID: 26908600 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

• 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.

  PMID: 32897040 BACKGROUND

• 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.

  PMID: 27115670 BACKGROUND

• 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.

  PMID: 22236582 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

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Maria Nolano, MD, PhD

  Istituti Clinici Scientifici Maugeri SpA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Nolano, MD, PhD

CONTACT

+390824909257; maria.nolano@icsmaugeri.it

Giuseppe Caporaso

CONTACT

+390824909645; giuseppe.caporaso@icsmaugeri.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: There are not masking participants
• 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: May 15, 2021
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)