Longitudinal Assessment of Autonomic and Sensory Nervous System in ALS

Обзор

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.

Вмешательства

• Диагностический тест Skin biopsy
  A punch skin biopsy of 3mm will be used to analyze cutaneous innervation
• Диагностический тест Cardiovascular Reflexes testing
  Cardiovascular reflex tests including deep breathing, head-up Tilt, standing, isometric exercises, mental arithmetic and Valsalva maneuver.
• Диагностический тест 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
• Диагностический тест Dinamic Sweat Test
  Test for the functional assessment of postganglionic sudomotor pathway

Первичные конечные точки

• Sensory peripheral innervation (IENF) [Срок оценки: At recruitment]
• Autonomic peripheral innervation [Срок оценки: At recruitment]
• Autonomic peripheral innervation [Срок оценки: At follow-up, an average of 6 months]
• Sensory peripheral innervation (IENF) [Срок оценки: At follow-up, an average of 6 months]

Вторичные конечные точки (4)

• Sensory and autonomic symptoms evaluated by clinical scales [Срок оценки: At the recruitment]
• Sensory and autonomic symptoms evaluated by clinical scales [Срок оценки: At follow-up, an average of 6 months]
• Assessment of Cardiovascular function [Срок оценки: baseline]
• Sudomotor function [Срок оценки: baseline]

Критерии участия

Критерии включения

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

Критерии исключения

• glucose intolerance or conditions potentially affecting the peripheral nervous system

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Италия · 2 центра

• ICS Maugeri - IRCCS of Telese Terme — Telese Terme
• Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Na — Naples

Публикации

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT05747937 · SBLAB/SLA20

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗