Longitudinal Assessment of Autonomic and Sensory Nervous System in ALS

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

Longitudinal Assessment of Autonomic and Sensory Nervous System in ALS

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05747937
• Other study ID #: SBLAB/SLA20
• Status: Recruiting
• Phase: N/A
• Start date: May 15, 2021
• Est. completion date: December 30, 2024

Study information

• Verified date: March 2024
• Source: Istituti Clinici Scientifici Maugeri SpA
• Contact: Maria Nolano, MD, PhD
• Phone: +390824909257
• Email: maria.nolano[@]icsmaugeri.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease

Intervention

Diagnostic Test:
• Skin biopsy
A punch skin biopsy of 3mm will be used to analyze cutaneous innervation
• Cardiovascular Reflexes testing
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
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
Test for the functional assessment of postganglionic sudomotor pathway

Locations

Country	Name	City	State
Italy	Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II	Napoli
Italy	ICS Maugeri - IRCCS of Telese Terme	Telese Terme	Benevento

Sponsors (1)

Lead Sponsor	Collaborator
Istituti Clinici Scientifici Maugeri SpA

Country where clinical trial is conducted

Italy, 

References & Publications (12)

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. — View 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. — View Citation

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. — View 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. — View Citation

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. — View Citation

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. — View 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. — View 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. — View 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. — View Citation

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. — View 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. — View 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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensory peripheral innervation (IENF)	Quantification Intraepidermal Nerve Fibers (IENF ff/mm) in skin biopsy from fingertip, thigh and leg.	At recruitment
Primary	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
Primary	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
Primary	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	Sensory and autonomic symptoms evaluated by clinical scales	Data of sensory and autonomic symptoms (Small fiber neuropathy Symptoms inventory questionnaire (SFN-SIQ) and Scale for Outcomes in Parkinson's disease for Autonomic Symptoms (SCOPA AUT)) will be collected	At the recruitment
Secondary	Sensory and autonomic symptoms evaluated by clinical scales	Data of sensory and autonomic symptoms (Small fiber neuropathy Symptoms inventory questionnaire (SFN-SIQ) and Scale for Outcomes in Parkinson's disease for Autonomic Symptoms (SCOPA AUT)) will be collected	At follow-up, an average of 6 months
Secondary	Assessment of Cardiovascular function	Data from cardiovascular reflex test will be analyzed and compared with morphological data and clinical motor severity	baseline
Secondary	Sudomotor function	Data from dinamic sweat test will be analyzed and compared with morphological data and clinical motor severity	baseline