Concentration and Attentional Deficits in POTS and Other Autonomic Neuropathies (POTSKog)

Understanding Impaired Concentration, Attentional Deficits and Their Pathophysiology in Postural Orthostatic Tachycardia Syndrome (POTS) and Other Autonomic Neuropathies (POTSKog-Study Aachen)

People with POTS, autoimmune autonomic neuropathy (AAN), pure autonomic failure (PAF), SFN and Ehlers Danlos Syndrome (EDS) do not only suffer from orthostatic symptoms such as dizziness, headache, neck pain, blurred vision or (pre-) syncope. They also experience deficits in attention and concentration (more precisely deficits in selective perspective, operating speed, executive functions and memory performance) mainly in upright position. Only few studies concerning cognitive impairment in autonomic neuropathies, their frequency, aetiology and therapy exist. Many patients concerned, especially with POTS, report attention deficits and "brain fog" with problems in their everyday life and work, predominantly in upright posture. Specific symptomatic or medical therapies do not exist. Medical treatment with Modafinil is discussed and part of a current study at Vanderbilt Autonomic Dysfunction Centre (1-5). The investigators want to investigate if problems of concentration, attention and/or cognitive dysfunction exist in people with POTS, AAN, SFN and EDS compared to healthy controls (HC). Thus the investigators use detailed clinical, autonomic and neuropsychological tests in different body positions (lying, sitting and standing) as also acute therapy (leg crossing).

Study Overview

• Status: Completed
• Conditions: Cognitive Impairment; Postural Tachycardia Syndrome; Dysautonomia; Pure Autonomic Failure; Ehlers-Danlos Syndrome; Autonomic Failure
• Intervention / Treatment: Procedure: leg crossing

Detailed Description

We are still recruting healthy controls and patients with autoimmune autonomic neuropathy in order to perform titl table examination and laboratory testing on day one, ono an empty stomach, without morning medication. Cognitive testing is performed on day two after randomization in three groups: lying, standing and standing with legs crossed.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Nordrhein Westfalen
    • Aachen, Nordrhein Westfalen, Germany, 52074
      • University Hospital, RWTH Aachen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• AAN, SFN, hEDS, POTS or healthy control
• diagnosis in our clinic on the basis of anamnesis, clinical data as neurological examination, tilt table, QST, skin biopsy, norepinephrine values, vitamine B12, antibodies

Exclusion Criteria:

for all participants

• pregnancy, nonage,severe heart insufficiency, deep brain Stimulation, pace maker, drug consumption, large fibre polyneuropathy for controls
• medication influencing blood pressure, psychiatric disease, synkopes or dizziness, neurological disorders esp. polyneuropathy, dementia, vitamine or iron deficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: lying; cognitive tests are performed during lying in all groups (SFN, AAN, EDS, POTS and controls)
No Intervention: standing; cognitive tests are performed during active Standing in all groups (SFN, AAN, EDS, POTS and controls)
Experimental: crossed legs; cognitive tests are performed during leg crossing in all groups (SFN, AAN, EDS, POTS and controls)	Procedure: leg crossing; As Counter maneuvre legs will be crossed and cognitive tests will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cognitive function: Stroop, TMT A und B	Change of results of cognitive function tests lying compared to standing and leg crossing	during intervention (Leg crossing)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
blood pressure Change (mmHg)	Change between blood pressure lying compared to compared to standing and leg crossing	during intervention (Leg crossing)
Heart frequency Change (B/min)	Change between heart frequency lying compared to compared to standing and leg crossing	during intervention (Leg crossing)
cerebral blood flow velocity	Change between cerebral blood flow compared to compared to standing and leg crossing	during intervention (Leg crossing)

Collaborators and Investigators

• Sponsor: RWTH Aachen University
• Investigators: Principal Investigator: Andrea Maier, Dr., Universitiy hospital RWTH Aachen, Department of Neurology

Publications and helpful links

General Publications

• Anderson JW, Lambert EA, Sari CI, Dawood T, Esler MD, Vaddadi G, Lambert GW. Cognitive function, health-related quality of life, and symptoms of depression and anxiety sensitivity are impaired in patients with the postural orthostatic tachycardia syndrome (POTS). Front Physiol. 2014 Jun 25;5:230. doi: 10.3389/fphys.2014.00230. eCollection 2014.
• Arnold AC, Haman K, Garland EM, Raj V, Dupont WD, Biaggioni I, Robertson D, Raj SR. Cognitive dysfunction in postural tachycardia syndrome. Clin Sci (Lond). 2015 Jan;128(1):39-45. doi: 10.1042/CS20140251.
• Stewart JM, Del Pozzi AT, Pandey A, Messer ZR, Terilli C, Medow MS. Oscillatory cerebral blood flow is associated with impaired neurocognition and functional hyperemia in postural tachycardia syndrome during graded tilt. Hypertension. 2015 Mar;65(3):636-43. doi: 10.1161/HYPERTENSIONAHA.114.04576. Epub 2014 Dec 15.
• Gibbons CH, Centi J, Vernino S, Freeman R. Autoimmune autonomic ganglionopathy with reversible cognitive impairment. Arch Neurol. 2012 Apr;69(4):461-6. doi: 10.1001/archneurol.2011.2372. Epub 2011 Dec 12.
• Guaraldi P, Poda R, Calandra-Buonaura G, Solieri L, Sambati L, Gallassi R, Cortelli P. Cognitive function in peripheral autonomic disorders. PLoS One. 2014 Jan 17;9(1):e85020. doi: 10.1371/journal.pone.0085020. eCollection 2014.
• Maier A, Schopen L, Thiel JC, Muller K, Fimm B, Schulz JB. Cognitive functioning in postural orthostatic tachycardia syndrome among different body positions: a prospective pilot study (POTSKog study). Clin Auton Res. 2023 Jun 1. doi: 10.1007/s10286-023-00950-0. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Actual): May 30, 2021
• Study Completion (Actual): May 30, 2023

Study Registration Dates

• First Submitted: September 10, 2018
• First Submitted That Met QC Criteria: September 20, 2018
• First Posted (Actual): September 21, 2018

Study Record Updates

• Last Update Posted (Actual): June 26, 2023
• Last Update Submitted That Met QC Criteria: June 23, 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; Nervous System Diseases; Skin Diseases; Disease; Congenital Abnormalities; Hematologic Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Connective Tissue Diseases; Hemostatic Disorders; Skin Diseases, Genetic; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Skin Abnormalities; Orthostatic Intolerance; Collagen Diseases; Syndrome; Tachycardia; Postural Orthostatic Tachycardia Syndrome; Primary Dysautonomias; Autonomic Nervous System Diseases; Pure Autonomic Failure; Ehlers-Danlos Syndrome
• Other Study ID Numbers: 17-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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