Longitudinal Assessment of Autonomic and Sensory Nervous System in ALS
Study Details
Study Description
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:
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Is autonomic dysfunction at diagnosis associated with disease progression and survival in patients with Amyotrophic Lateral Sclerosis ?
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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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Amyotrophic Lateral Sclerosis patients Amyotrophic Lateral Sclerosis (ALS) patients within 18 months from symptoms onset will be recruited |
Diagnostic Test: Skin biopsy
A punch skin biopsy of 3mm will be used to analyze cutaneous innervation
Diagnostic Test: Cardiovascular Reflexes testing
Cardiovascular reflex tests including deep breathing, head-up Tilt, standing, isometric exercises, mental arithmetic and Valsalva maneuver.
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
Diagnostic Test: Dinamic Sweat Test
Test for the functional assessment of postganglionic sudomotor pathway
|
| Active Comparator: Healthy controls A population of healthy controls matched for sex and age will be enrolled |
Diagnostic Test: Skin biopsy
A punch skin biopsy of 3mm will be used to analyze cutaneous innervation
Diagnostic Test: Cardiovascular Reflexes testing
Cardiovascular reflex tests including deep breathing, head-up Tilt, standing, isometric exercises, mental arithmetic and Valsalva maneuver.
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
Diagnostic Test: Dinamic Sweat Test
Test for the functional assessment of postganglionic sudomotor pathway
|
Outcome Measures
Primary Outcome Measures
- Sensory peripheral innervation (IENF) [At recruitment]
Quantification Intraepidermal Nerve Fibers (IENF ff/mm) in skin biopsy from fingertip, thigh and leg.
- Autonomic peripheral innervation [At recruitment]
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.
- Autonomic peripheral innervation [At follow-up, an average of 6 months]
Quantification sweat gland (fiber lenght/um3) and arrector pili muscle (ff/mm) innervation in skin biopsy from thigh.
- Sensory peripheral innervation (IENF) [At follow-up, an average of 6 months]
Quantification Intraepidermal Nerve Fibers (IENF ff/mm) in skin biopsy from thigh.
Secondary Outcome Measures
- Sensory and autonomic symptoms evaluated by clinical scales [At the recruitment]
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
- Sensory and autonomic symptoms evaluated by clinical scales [At follow-up, an average of 6 months]
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
- Assessment of Cardiovascular function [baseline]
Data from cardiovascular reflex test will be analyzed and compared with morphological data and clinical motor severity
- Sudomotor function [baseline]
Data from dinamic sweat test will be analyzed and compared with morphological data and clinical motor severity
Eligibility Criteria
Criteria
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
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 |
Sponsors and Collaborators
- Istituti Clinici Scientifici Maugeri SpA
Investigators
- Principal Investigator: Maria Nolano, MD, PhD, Istituti Clinici Scientifici Maugeri SpA
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- SBLAB/SLA20