Controlled CO2 Inhalation in NOH (CO2-nOH)

Controlled CO2 Inhalation to Increase Blood Pressure in Neurogenic Orthostatic Hypotension: a Proof-of-Concept Novel Therapy Study

This study focuses on neurogenic orthostatic hypotension (nOH), which is a disorder characterized by an abnormal drop in blood pressure (BP) within 3-minutes of standing. Patients with nOH experience debilitating symptoms including light-headedness, falls, and fainting. Patients often struggle with day-to-day tasks that require standing, with a reduced quality-of-life. Current therapies for nOH have limited effectiveness and unwanted side effects. Our lab has found that raising blood CO2 levels (hypercapnia) in the lab increases BP when standing in patients with nOH. We now aim to test the CarboHaler, an exogenous controlled CO2 delivery device, in this study to see if increasing CO2 levels through controlled CO2 inhalation can improve BP and reduce symptoms in patients with nOH when standing up. On the study day, participants will undergo two Head-up Tilt (HUT; upright) tests with different breathing protocols: one with and one without exogenous CO2 delivery provided by a CO2 inhalational device. We will record heart rate, blood pressure, and breathing parameters. We will also assess upright symptoms using the Vanderbilt Orthostatic Symptoms Score. Our primary outcome is the magnitude of the change in systolic BP from lying down to standing, which will be compared with and without exogenous CO2 delivery. We hypothesize that exogenous CO2 delivery provided by a CO2 inhalational device will raise CO2 enough to increase standing BP, which could reduce the debilitating symptoms experienced by patients with nOH. We hope that these data will support future clinical trials, with the long-term goal of creating a simple, low-cost treatment for increasing quality-of-life for patients with nOH.

Study Overview

• Status: Not yet recruiting
• Conditions: Neurogenic Orthostatic Hypotension
• Intervention / Treatment: Device: Controlled CO2 delivery (Sham); Other: Controlled CO2 delivery

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary
      • Contact: Rasha Hamzeh, RN; Phone Number: 4032208897; Email: autonomic.research@ucalgary.ca
      • Contact: Satish Raj, MD MSCI; Phone Number: 4032106152; Email: autonomic.research@ucalgary.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• Other factors which in the investigator's opinion would prevent the participant from completing the protocol, including poor compliance during previous studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: 0% CO2 Arm; In this arm, participants will breathe with the CO2 delivery device providing no exogenous CO2 while supine and during a 10-min HUT test.	Device: Controlled CO2 delivery (Sham); For this intervention, we will be using this device set at 0% CO2 for our sham comparison.
Experimental: Controlled CO2 Inhalation Arm; In this arm, participants will breathe with the CO2 delivery device in the supine position until BP levels increase. Once a BP increase is observed, participants will be tilted upright and will continue to breathe with the inhalation device during a 10-min HUT test.	Other: Controlled CO2 delivery; The use of a controlled CO2 delivery offers a straightforward way to increase arterial CO2. Controlled CO2 inhalation may offer a novel hemodynamic therapy for patients with Neurogenic Orthostatic Hypotension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnitude of the systolic blood pressure (SBP) response	The primary outcome measures will be the magnitude of the systolic blood pressure (SBP) response (ΔSBP = Head Up Tilt - Supine) during 0% CO2 vs. Controlled CO2 inhalation.	Start of in-lab study day to the end of the in-lab study day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cerebral Blood Flow (ΔCBFv)	Secondary outcome measures will be the change in Cerebral Blood Flow (ΔCBFv) for each arm of the study.	Start of in-lab study day to the end of the in-lab study day
Change in Vanderbilt Orthostatic Symptom Scores (ΔVOSS)	Secondary outcome measures will be the change in Vanderbilt Orthostatic Symptom Scores (ΔVOSS) for each arm of the study.	Start of in-lab study day to the end of the in-lab study day

Collaborators and Investigators

• Sponsor: University of Calgary

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: December 20, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 20, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Cardiovascular; Novel; Autonomic; Quality-of-life; Neurogenic Orthostatic Hypotension; Symptom-management; Therapies
• Additional Relevant MeSH Terms: Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Orthostatic Intolerance; Hypotension; Hypotension, Orthostatic
• Other Study ID Numbers: REB24-1780

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
• product manufactured in and exported from the U.S.: No