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

NCT04310644 | Recruiting

• 1 other identifier: 19-016
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Autonomic Neuropathy; Ehlers-Danlos Syndrome Hypermobility Type; Small Fiber Neuropathy; Postural Tachycardia Syndrome

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (5)

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

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

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

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.

Interventions

No intervention planned, but all patients get our standart treatment OTHER

Patients are selected from clinical Routine and get our standart Treatment based on their disease

Autoimmune autonomic neuropathy/Pure autonomic failure; Ehlers Danlos Syndrome; Postural Orthostatic Tachycardia Syndrome

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• RWTH Aachen University: lead
• DLR German Aerospace Center: collaborator

Study Sites (1)

University clinic RWTH Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

RECRUITING

Related Publications (2)

• Igharo D, Thiel JC, Rolke R, Akkaya M, Weis J, Katona I, Schulz JB, Maier A. Skin biopsy reveals generalized small fibre neuropathy in hypermobile Ehlers-Danlos syndromes. Eur J Neurol. 2023 Mar;30(3):719-728. doi: 10.1111/ene.15649. Epub 2022 Dec 13.

  PMID: 36437696 DERIVED

• Gerlach DA, Maier A, Manuel J, Bach A, Hoff A, Honemann JN, Heusser K, Voit D, Frahm J, Jordan J, Tank J. Real-Time Magnetic Resonance Imaging to Study Orthostatic Intolerance Mechanisms in Human Beings: Proof of Concept. J Am Heart Assoc. 2022 Nov;11(21):e026437. doi: 10.1161/JAHA.122.026437. Epub 2022 Oct 27.

  PMID: 36300662 DERIVED

Related 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

MeSH Terms

Conditions

Ehlers-Danlos syndrome type 3; Small Fiber Neuropathy; Postural Orthostatic Tachycardia Syndrome

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases

Study Officials

• Andrea Maier

  University Hospital, Aachen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea Maier, physician

CONTACT

+492418089600; ans-ambulanz@ukaachen.de

Denver Igharo, student

CONTACT

+492418089600; ans-ambulanz@ukaachen.de

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Primary Investigator and attending physician

Study Record Dates

• First Submitted: March 13, 2020
• First Posted: March 17, 2020
• Study Start: September 15, 2019
• Primary Completion (Estimated): September 15, 2028
• Study Completion (Estimated): September 15, 2029
• Last Updated: February 4, 2025

Record last verified: 2025-02

Locations

DE (1)