Longitudinal Assessment of Autonomic and Sensory Nervous System in ALS

Study Overview
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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.

Official Title
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Longitudinal Assessment of Autonomic and Sensory Nervous System in ALS

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* 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


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amyotrophic Lateral Sclerosis patients<br>Amyotrophic Lateral Sclerosis (ALS) patients within 18 months from symptoms onset will be recruited | Diagnostic Test: Skin biopsy<br>* A punch skin biopsy of 3mm will be used to analyze cutaneous innervation<br>Diagnostic Test: Cardiovascular Reflexes testing<br>* Cardiovascular reflex tests including deep breathing, head-up Tilt, standing, isometric exercises, mental arithmetic and Valsalva maneuver.<br>Diagnostic Test: Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms<br>* We'll characterize patients' symptoms through the administration of clinical scales such as: SCOPA-AUT autonomic symptoms scale; Brief Pain Inventory questionnaire<br>Diagnostic Test: Dinamic Sweat Test<br>* Test for the functional assessment of postganglionic sudomotor pathway<br>|
| Active Comparator: Healthy controls<br>A population of healthy controls matched for sex and age will be enrolled | Diagnostic Test: Skin biopsy<br>* A punch skin biopsy of 3mm will be used to analyze cutaneous innervation<br>Diagnostic Test: Cardiovascular Reflexes testing<br>* Cardiovascular reflex tests including deep breathing, head-up Tilt, standing, isometric exercises, mental arithmetic and Valsalva maneuver.<br>Diagnostic Test: Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms<br>* We'll characterize patients' symptoms through the administration of clinical scales such as: SCOPA-AUT autonomic symptoms scale; Brief Pain Inventory questionnaire<br>Diagnostic Test: Dinamic Sweat Test<br>* Test for the functional assessment of postganglionic sudomotor pathway<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Assessment of Cardiovascular function | Data from cardiovascular reflex test will be analyzed and compared with morphological data and clinical motor severity | baseline | 
| Sudomotor function | Data from dinamic sweat test will be analyzed and compared with morphological data and clinical motor severity | baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autonomic nervous system, skin biopsy, biomarkers, cutaneous sensory an autonomic innervation