Autonomic Small Fiber Neuropathy and Ehlers Danlos Syndromes - Prospective Study and Registry (ProANS)

Autonomic Neuropathy and Its Pathophysiology in Autoimmune Autonomic Neuropathies, Postural Orthostatic Tachycardia Syndrome and Ehlers Danlos Syndromes: Peripheral Autonomic Small Fiber Neuropathy or Central Autonomic Failure? Validation of the Malmö POTS Score and a Better Diagnosis of POTS in Patientes With Autnomic Failure (VaGeMAPS-3-step-Diag)

We examine patients with different autonomic neuropathies and Ehlers Danlos syndromes compared to healthy controls at three different points over time (baseline, after 3 months and after 1.5 years) to gain knowledge about the course of this disease and understand its pathophysiology, with a focus on Small Fiber neuropathy. Moreover we will validate the german version of the Malmö POTS Score and establish an easy diagnostic scheme for patients in outpatient care.

Study Overview

• Status: Recruiting
• Conditions: Postural Tachycardia Syndrome; Autonomic Neuropathy; Small Fiber Neuropathy; Ehlers-Danlos Syndrome Hypermobility Type
• Intervention / Treatment: Other: No intervention planned, but all patients get our standart treatment

Detailed Description

Inclusion of patients with autoimmune autonomic neuropathies/ pure autonomic failure, postural orthostatic tachycardia syndrome, small fiber neuropathies, Ehlers-Danlos syndromes, Mast cell activation syndrom, Chronic fatigue syndrome and PostCOVID syndrome in our Registry study with follow up visits. Comparison to healthy controls concerning selected examinations.

Planned examinations are laboratory tests, questionnaires on mental and physical health status and circulatory disorders, attention tests, tilt table testing, standing test, sweat function, investigation of small fiber function via quantitative sensory testing as well as the density of nerve fibers in the skin. Measurements are performed at baseline mostly in clinical routine and follow up visits are offered.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Andrea Maier, physician; Phone Number: +492418089600 +492418089600; Email: ans-ambulanz@ukaachen.de
• Study Contact Backup: Name: Denver Igharo, student; Phone Number: +492418089600 +492418089600; Email: ans-ambulanz@ukaachen.de

Study Locations

• Germany
  • Nordrhein Westfalen
    • Aachen, Nordrhein Westfalen, Germany, 52074
      • Recruiting
      • University clinic RWTH Aachen
      • Contact: Andrea Maier, physician; Phone Number: +492418089600 +492418089600; Email: ans-ambulanz@ukaachen.de
      • Contact: Denver Igharo, student; Phone Number: +492418089600 +492418089600; Email: ans-ambulanz@ukaachen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

We will include patients with above mentioned disease who are diagnosed and treated in our outpatient clinic for autonomic disorders in Aachen, Germany.

Description

Inclusion Criteria:

• autonomic neuropathy
• Postural orthostatic tachycardia syndrome
• hypermobile or classical Ehlers Danlos syndromes
• Chronic fatigue syndrome, mast cell activation syndrome and/or PostCOVID
• healty controls
• between 18-80 years
• in patients: diagnosis and clinical testing in our outpatient clinic
• German speaking

Exclusion Criteria:

• pregnancy
• Pacemaker or Deep brain Stimulation
• sensory or motor Polyneuropathy
• neurodegenerative disease

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Postural Orthostatic Tachycardia Syndrome; Patients with orthostatic intolerance because of Postural orthostatic tachycardia syndrome diagnosed in our outpatient clinic by tilt table examination.	Other: No intervention planned, but all patients get our standart treatment; Patients are selected from clinical Routine and get our standart Treatment based on their disease
Ehlers Danlos Syndrome; Patients with hypermobile or classical EDS who are already diagnosed including genetical testing for classical or vascular EDS and Marfan Syndromes	Other: No intervention planned, but all patients get our standart treatment; Patients are selected from clinical Routine and get our standart Treatment based on their disease
Autoimmune autonomic neuropathy/Pure autonomic failure; Patients who have an autoimmune autonomic neuropathy based on clinical diagnosis and antibody testing in our outpatient clinic. Cardial MIBG Scintigraphy should have been performed.	Other: No intervention planned, but all patients get our standart treatment; Patients are selected from clinical Routine and get our standart Treatment based on their disease
Healthy controls; Healthy controls with no documented cardiovascular or neurological disorders and no symtoms of autonomic failure/dizziness/fainting
others; Patients who have comorbidities as mast cell activation syndrome, chronic fatigue and/or Post COVID syndrome, based on clinical diagnosis in our outpatient clinic.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure	Change in systolic and diastolic blood pressure over time	baseline, 3 months and 18 months
Heart frequency	Change in heart frequency over time	baseline, 3 months and 18 months
Skin biopsy	intraepithelial nerve fiber density between groups	baseline
Composite autonomic severity Score	Change of the Score over time, the results are interpreted as normal (score=0), mild (score=1-3), moderate (score=4-6) or severe (score=7-10)	baseline, 3 months and 18 months

Collaborators and Investigators

• Sponsor: RWTH Aachen University
• Collaborators: DLR German Aerospace Center
• Investigators: Principal Investigator: Andrea Maier, University Hospital, Aachen

Publications and helpful links

Helpful Links

• official homepage of our outpatient clinic for autonomic nervous system disorders
• Paper Skin biopsy reveals generalized small fibre neuropathy in hypermobile Ehlers-Danlos syndromes

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2019
• Primary Completion (Estimated): September 15, 2024
• Study Completion (Estimated): September 15, 2029

Study Registration Dates

• First Submitted: March 13, 2020
• First Submitted That Met QC Criteria: March 13, 2020
• First Posted (Actual): March 17, 2020

Study Record Updates

• Last Update Posted (Actual): July 5, 2023
• Last Update Submitted That Met QC Criteria: June 30, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Disease; Congenital Abnormalities; Hematologic Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Connective Tissue Diseases; Neuromuscular Diseases; Hemostatic Disorders; Skin Diseases, Genetic; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Autonomic Nervous System Diseases; Skin Abnormalities; Primary Dysautonomias; Orthostatic Intolerance; Collagen Diseases; Syndrome; Peripheral Nervous System Diseases; Nervous System Diseases; Tachycardia; Postural Orthostatic Tachycardia Syndrome; Ehlers-Danlos Syndrome; Small Fiber Neuropathy
• Other Study ID Numbers: 19-016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No