Hypercapnia and Orthostatic Tolerance in Postural Orthostatic Tachycardia Syndrome

NCT04271878 | Recruiting

• 1 other identifier: REB20-0135
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The mechanism behind postural orthostatic tachycardia syndrome (POTS) involves many causes including a sympathetic nervous system problem. Blood gases, like carbon dioxide (CO2), have an important effect on sympathetic activation. The purpose of this research study is to determine if higher CO2 levels have any effect in lowering heart rate and reducing POTS symptoms when upright/standing. The investigators are also searching for the ideal CO2 concentration to achieve the most effective response

Conditions

Postural Tachycardia Syndrome; Orthostatic Intolerance

Keywords

postural tachycardia; autonomic; orthostatic intolerance; dysautonomia

Outcome Measures

Primary Outcomes (1)

• Heart Rate (HR) variation

  Magnitude of ΔHR

  difference between HR from supine to peak HR during tilt test for each intervention (mean value HR between the 8th and 9th minute of supine; peak parameters, during HUTT, mean value during the first min and between the 3rd and 8th min)

Secondary Outcomes (2)

• Cerebral blood flow velocity (CBFv) variation

  difference between CBFv from supine to peak during tilt test for each intervention (mean value CBFv between the 8th and 9th min of supine; peak parameters, during HUTT, mean value CBFv during the first min and between the 3rd and 8th min)

• VOSS symptom score

  VOSS will be accessed at the 8th minute of each HUTT, comparing the intensity of symptoms in each intervention

Study Arms (1)

All participants

OTHER

All participants will receive the same interventions

Other: RespirAct™ system (Thornhill Research Inc., Toronto, Canada)

Interventions

RespirAct™ system (Thornhill Research Inc., Toronto, Canada) OTHER

1. HUTT with Normal Breathing in Room Air (No gas interventions will be applied) 2. HUTT with Normal Breathing and ETCO2 clamped at baseline levels 3. HUTT with Normal Breathing and Mild Hypercapnia (the ETCO2 will be clamped at 45mmHg ) 4. HUTT with Normal Breathing and High Hypercapnia (the ETCO2 will be clamped at 55mmHg) 5. HUTT with Fast, Deep Breathing and resultant Hypocapnia Participant will be coached to breath around 15 breath per min.No gas interventions will be applied 6. HUTT with Fast, Deep Breathing and ETCO2 clamped at baseline levels. Participant will be coached to breath around 15 breath per min, with ETCO2 clamped to baseline levels.

All participants

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Physician diagnosis of Postural Tachycardia Syndrome (POTS)
• Age 18-60 years
• Male and Female
• Non - smokers.
• Able and willing to provide informed consent.
• Ability to travel to Libin Cardiovascular Institute of Alberta Autonomic Testing Lab at the University of Calgary, Calgary, AB.

You may not qualify if:

• Overt cause for postural tachycardia, i.e., acute dehydration
• Participants with somatization or severe anxiety symptoms will be excluded
• Pregnant
• Inability to tolerate mask for the duration of the study
• Subjects who require portable oxygen at rest or with exercise
• Subjects with chronic heart failure or severe pulmonary disease who are unable to climb one flight of stairs due to shortness of breath.
• Other factors which in the investigator's opinion would prevent the participant from completing the protocol, including poor compliance during previous studies.

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

RECRUITING

Related Publications (5)

• Del Pozzi AT, Schwartz CE, Tewari D, Medow MS, Stewart JM. Reduced cerebral blood flow with orthostasis precedes hypocapnic hyperpnea, sympathetic activation, and postural tachycardia syndrome. Hypertension. 2014 Jun;63(6):1302-8. doi: 10.1161/HYPERTENSIONAHA.113.02824. Epub 2014 Apr 7.

  PMID: 24711524 BACKGROUND

• Ocon AJ, Medow MS, Taneja I, Clarke D, Stewart JM. Decreased upright cerebral blood flow and cerebral autoregulation in normocapnic postural tachycardia syndrome. Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H664-73. doi: 10.1152/ajpheart.00138.2009. Epub 2009 Jun 5.

  PMID: 19502561 BACKGROUND

• Taneja I, Medow MS, Clarke DA, Ocon AJ, Stewart JM. Baroreceptor unloading in postural tachycardia syndrome augments peripheral chemoreceptor sensitivity and decreases central chemoreceptor sensitivity. Am J Physiol Heart Circ Physiol. 2011 Jul;301(1):H173-9. doi: 10.1152/ajpheart.01211.2010. Epub 2011 May 2.

  PMID: 21536847 BACKGROUND

• Stewart JM, Pianosi P, Shaban MA, Terilli C, Svistunova M, Visintainer P, Medow MS. Postural Hyperventilation as a Cause of Postural Tachycardia Syndrome: Increased Systemic Vascular Resistance and Decreased Cardiac Output When Upright in All Postural Tachycardia Syndrome Variants. J Am Heart Assoc. 2018 Jun 30;7(13):e008854. doi: 10.1161/JAHA.118.008854.

  PMID: 29960989 BACKGROUND

• Novak P. Hypocapnic cerebral hypoperfusion: A biomarker of orthostatic intolerance. PLoS One. 2018 Sep 26;13(9):e0204419. doi: 10.1371/journal.pone.0204419. eCollection 2018.

  PMID: 30256820 RESULT

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome; Orthostatic Intolerance; Autonomic Nervous System Diseases

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Satish R Raj, MD, MSCI

  University of Calgary, Cardiac Science

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shaun Ranada, BSc

CONTACT

403-210-6152; shaun.ranada@ucalgary.ca

Rasha Hamza, RN

CONTACT

403-210-6152; autonomic.research@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: All participants will be fitted with a face mask connected to a tube supplied with gas from the RespirAct™ system. The participants will not be informed about the concentration of gases during the tilt tests. After the study completion they will be informed about the order of interventions.
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants must have been diagnosed with POTS, they will all complete up to 6 head-up tilt tests (HUTTs) on a single day. They will all receive the following interventions: 1. Normal not coached breathing and room air 2. Normal not coached breathing with ETCO2 clamped at baseline levels - The baseline CO2 levels will be defined from the mean end-tidal CO2 (ETCO2) measured through the mask over the last 5 min of the first baseline phase (ETCO2 normal values range between 35mmHg and 45mmHg). 3. Normal not coached breathing with mild ETCO2 levels (45mmHg) 4. Normal not coached breathing with high ETCO2 levels (55mmHg) 5. Fast breathing and resultant low ETCO2 levels (target ETCO2 19-24mmHg); 6. Fast breathing and ETCO2 clamped at baseline levels

Study Record Dates

• First Submitted: February 10, 2020
• First Posted: February 17, 2020
• Study Start: February 2, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)