CO2 Rebreathing in nOH: A Proof-of-Concept Pilot Study

NCT05908760 | Recruiting

• 1 other identifier: REB23-0791
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Neurogenic orthostatic hypotension (nOH) is a chronic condition associated with increased cardiovascular risk and reduced quality of life. On standing, patients with nOH experience a large reduction in blood pressure (BP; at least ≥20/10mmHg, but often much more), which is often accompanied by debilitating symptoms and syncope. A previous study (unpublished) showed that hypercapnia significantly increases standing BP in patients with nOH. Human bodies naturally produce and exhale CO2. Rebreathe devices offer a simple, cost-effective technology to increase arterial CO2. In brief, rebreathe devices work by capturing expired CO2, which is then re-inhaled. The net effect is a transient increase in CO2. A CO2 rebreathing device may offer a novel hemodynamic therapy for patients with nOH. This is a pilot, proof-of-concept study to evaluate a CO2 rebreather to improve blood pressure and orthostatic tolerance in patients with nOH. The hypothesis is that a rebreather will increase CO2 sufficiently enough to improve BP in patients with nOH. Male and female patients (n=28) will be asked to complete two randomized 70° head-up tilt (HUT) tests breathing either room air or using a CO2 rebreather. Hemodynamics (BP, heart rate, stroke volume, brain blood flow) and orthostatic symptoms will be assessed throughout. Breath-by-breath data will include O2, CO2, respiration rate and tidal volume. The primary outcome measure will be the magnitude of the BP response (ΔBP = HUT - Supine) during Room Air vs. Hypercapnia. The primary outcome will be compared between room air and hypercapnia using a paired t-test.

Conditions

Neurogenic Orthostatic Hypotension; Autonomic Failure

Outcome Measures

Primary Outcomes (1)

• Δ Blood Pressure (BP)

  Magnitude of ΔBP (HUT-Supine) breathing room air vs CO2 rebreathe

  The ΔBP (HUT-Supine) calculated as the average BP in the final two minutes of supine baseline and the average BP between minute 3 and 5 of HUT will be compared between room air and CO2 rebreathe

Secondary Outcomes (2)

• Δ Vanderbilt Orthostatic Symptom Score [Range: 0 (absent) to 10 (worst)]

  The Δ Vanderbilt Orthostatic Symptom Score (symptoms at the 5th minute of HUT - symptoms at the 5th minute of supine rest) will be compared between room air vs CO2 rebreathe

• Δ Cerebral Blood Flow Velocity (CBFv)

  The ΔCBFv (HUT-Supine) calculated as the average CBFv in the final two minutes of supine baseline and the average CBFv between minute 3 and 5 of HUT will be compared between room air and CO2 rebreathe

Study Arms (2)

CO2 Rebreathing

EXPERIMENTAL

Participants will breathe with the rebreather in the supine position until CO2 levels increase between 5-10mmHg. Once CO2 levels are increased, participants will be tilted upright, and will continue to breathe with the rebreather during a 5-min HUT test

Device: CO2 ReHaler

Room Air

NO INTERVENTION

Participants will breathe room air in the supine position and during a 5-min HUT test

Interventions

CO2 ReHaler DEVICE

The ReHaler captures expired CO2, which is then re-inhaled. The net effect is a transient increase in CO2.

CO2 Rebreathing

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Male and Female
• Physician diagnosis of Neurogenic Orthostatic Hypotension
• Non-smokers.
• Able and willing to provide informed consent.
• Ability to travel to Libin Cardiovascular Institute Autonomic Testing Lab at the University of Calgary, Calgary, AB.

You may not qualify if:

• Medical therapies or medications which could interfere with testing of autonomic function
• Pregnant or breast-feeding females
• Subjects with chronic heart failure or severe pulmonary disease who are unable to climb one flight of stairs due to shortness of breath.
• Presence of failure of other organ systems or systemic illness that can affect autonomic function or the participant's ability to cooperate. These include dementia, alcohol and/or drug abuse, cerebrovascular disease, kidney or liver disease, surgical procedures where the nerves of the sympathetic nervous system have been cut.
• 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, Canada

RECRUITING

Related Publications (5)

• Freeman R, Abuzinadah AR, Gibbons C, Jones P, Miglis MG, Sinn DI. Orthostatic Hypotension: JACC State-of-the-Art Review. J Am Coll Cardiol. 2018 Sep 11;72(11):1294-1309. doi: 10.1016/j.jacc.2018.05.079.

  PMID: 30190008 BACKGROUND

• Morgan BJ, Crabtree DC, Palta M, Skatrud JB. Combined hypoxia and hypercapnia evokes long-lasting sympathetic activation in humans. J Appl Physiol (1985). 1995 Jul;79(1):205-13. doi: 10.1152/jappl.1995.79.1.205.

  PMID: 7559221 BACKGROUND

• Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS, Hainsworth R, Hilz MJ, Jacob G, Kaufmann H, Jordan J, Lipsitz LA, Levine BD, Low PA, Mathias C, Raj SR, Robertson D, Sandroni P, Schatz I, Schondorff R, Stewart JM, van Dijk JG. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011 Apr;21(2):69-72. doi: 10.1007/s10286-011-0119-5. No abstract available.

  PMID: 21431947 BACKGROUND

• Shoemaker JK, Vovk A, Cunningham DA. Peripheral chemoreceptor contributions to sympathetic and cardiovascular responses during hypercapnia. Can J Physiol Pharmacol. 2002 Dec;80(12):1136-44. doi: 10.1139/y02-148.

  PMID: 12564639 BACKGROUND

• Fuglsang CH, Johansen T, Kaila K, Kasch H, Bach FW. Treatment of acute migraine by a partial rebreathing device: A randomized controlled pilot study. Cephalalgia. 2018 Sep;38(10):1632-1643. doi: 10.1177/0333102418797285. Epub 2018 Aug 22.

  PMID: 30134739 BACKGROUND

MeSH Terms

Conditions

Pure Autonomic Failure

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases

Study Officials

• Satish R Raj, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jacquie Baker, PhD

CONTACT

4032103819; autonomic.research@ucalgary.ca

Angela Qi, MD

CONTACT

4032107627; autonomic.research@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Male and female NOH patients (n=28) will be recruited from the Calgary Autonomic Clinic. Participants will complete the following two randomized head-up tilt tests (HUT): * Room Air: Participants will breathe room air while supine and during a 5-min HUT test * CO2 rebreathing: Participants will breathe with the rebreather in the supine position until CO2 levels increase between 5-10mmHg. Once CO2 levels are increased, participants will be tilted upright, and will continue to breathe with the rebreather during a 5-min HUT test

Study Record Dates

• First Submitted: June 8, 2023
• First Posted: June 18, 2023
• Study Start: July 30, 2024
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)