Autonomic NeuropathyProANSNCT04310644
Autonomic Small Fiber Neuropathy and Ehlers Danlos Syndromes - Prospective Study and Registry
An observational study of Autonomic Neuropathy and Ehlers-Danlos Syndrome Hypermobility Type, run by RWTH Aachen University at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Autonomic Neuropathy, Ehlers-Danlos Syndrome Hypermobility Type, Small Fiber Neuropathy
- How many people
- 200 participants
- Where
- 1 siteGermany
- Study dates
- 15 Sep 2019to 15 Sep 2029
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- pregnancy
- Pacemaker or Deep brain Stimulation
- sensory or motor Polyneuropathy
- neurodegenerative disease
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
University clinic RWTH Aachen
Aachen, North Rhine-Westphalia, 52074
Andrea Maier, physician, +492418089600 ext. +492418089600, ans-ambulanz@ukaachen.de
Denver Igharo, student, +492418089600 ext. +492418089600, ans-ambulanz@ukaachen.de
About this study
Official title: 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.
Read the 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.
- Conditions
- Autonomic Neuropathy, Ehlers-Danlos Syndrome Hypermobility Type, Small Fiber Neuropathy, Postural Tachycardia Syndrome
- Being tested
- No intervention planned, but all patients get our standart treatment
- Medical subject headings
- Ehlers-Danlos syndrome type 3, Small Fiber Neuropathy, Postural Orthostatic Tachycardia Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No intervention planned, but all patients get our standart treatmentOther
Patients are selected from clinical Routine and get our standart Treatment based on their disease
| Study group | Role | What they receive |
|---|---|---|
| Postural Orthostatic Tachycardia Syndrome | Patients with orthostatic intolerance because of Postural orthostatic tachycardia syndrome diagnosed in our outpatient clinic by tilt table examination. Receives: 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 Receives: 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood pressure
Change in systolic and diastolic blood pressure over time
Measured: baseline, 3 months and 18 months
Heart frequency
Change in heart frequency over time
Measured: baseline, 3 months and 18 months
Skin biopsy
intraepithelial nerve fiber density between groups
Measured: 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)
Measured: baseline, 3 months and 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2020
- Study start15 Sep 2019
- Primary completion15 Sep 2028 (estimated)
- Study completion15 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Autonomic NeuropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- RWTH Aachen University
- Sponsor type
- University, hospital or other
- Collaborators
- DLR German Aerospace Center
- Responsible party
- Principal investigator, Andrea Maier, RWTH Aachen University
- Investigators
- Andrea Maier, Principal investigator, University Hospital, Aachen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04310644
- Sponsor's protocol ID
- 19-016
- Acronym
- ProANS
- Status last verified
- Feb 2025
- First submitted
- 13 Mar 2020
- Last updated
- 4 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 36437696Gerlach 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.
PubMed 36300662
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT04310644
- Acronym / sponsor ID
- ProANS / 19-016
- Conditions
- Autonomic Neuropathy, Ehlers-Danlos Syndrome Hypermobility Type, Small Fiber Neuropathy, Postural Tachycardia Syndrome
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- RWTH Aachen UniversityUniversity, hospital or other
- Collaborators
- DLR German Aerospace Center
- Study start
- 15 Sep 2019 (actual)
- Primary completion
- 15 Sep 2028 (estimated)
- Study completion
- 15 Sep 2029 (estimated)
- First posted
- 17 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 5 Years
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Postural Orthostatic Tachycardia Syndrome | – | Other: No intervention planned, but all patients get our standart treatmentPatients with orthostatic intolerance because of Postural orthostatic tachycardia syndrome diagnosed in our outpatient clinic by tilt table examination. |
| Ehlers Danlos Syndrome | – | Other: No intervention planned, but all patients get our standart treatmentPatients with hypermobile or classical EDS who are already diagnosed including genetical testing for classical or vascular EDS and Marfan Syndromes |
| Autoimmune autonomic neuropathy/Pure autonomic failure | – | Other: No intervention planned, but all patients get our standart treatmentPatients who have an autoimmune autonomic neuropathy based on clinical diagnosis and antibody testing in our outpatient clinic. Cardial MIBG Scintigraphy should have been performed. |
| 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (8 listed)
- autonomic neuropathy
- Postural orthostatic tachycardia syndrome
- hypermobile or classical Ehlers Danlos syndromes
- Chronic fatigue syndrome, mast cell activation syndrome and/or PostCOVID
- healty controls
Key exclusion criteria (4 listed)
- pregnancy
- Pacemaker or Deep brain Stimulation
- sensory or motor Polyneuropathy
- neurodegenerative disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No intervention planned, but all patients get our standart treatmentPatients are selected from clinical Routine and get our standart Treatment based on their disease | Other | Autoimmune autonomic neuropathy/Pure autonomic failure, Ehlers Danlos Syndrome, Postural Orthostatic Tachycardia Syndrome |
Primary outcome
Blood pressure
Time frame: baseline, 3 months and 18 months
Change in systolic and diastolic blood pressure over time
Heart frequency
Time frame: baseline, 3 months and 18 months
Change in heart frequency over time
Skin biopsy
Time frame: baseline
intraepithelial nerve fiber density between groups
Composite autonomic severity Score
Time frame: baseline, 3 months and 18 months
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
- Derived from this study: PubMed 36437696Igharo 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.
- Derived from this study: PubMed 36300662Gerlach 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.
- official homepage of our outpatient clinic for autonomic nervous system disordersLink provided by the sponsor.
- Paper Skin biopsy reveals generalized small fibre neuropathy in hypermobile Ehlers-Danlos syndromesLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Andrea Maier principal investigator
University Hospital, Aachen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Autonomic Neuropathy and Ehlers-Danlos Syndrome Hypermobility Type, run by RWTH Aachen University at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Andrea Maier, physician (+492418089600 ext. +492418089600, ans-ambulanz@ukaachen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood pressure (time frame: baseline, 3 months and 18 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04310644, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.