Controlled CO2 Inhalation in NOH

Official title

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

Overview

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.

Interventions

• 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
• Device Controlled CO2 delivery (Sham)
  For this intervention, we will be using this device set at 0% CO2 for our sham comparison.

Primary outcome measures

• Magnitude of the systolic blood pressure (SBP) response [Time frame: Start of in-lab study day to the end of the in-lab study day]

Secondary outcome measures (2)

• Change in Cerebral Blood Flow (ΔCBFv) [Time frame: Start of in-lab study day to the end of the in-lab study day]
• Change in Vanderbilt Orthostatic Symptom Scores (ΔVOSS) [Time frame: Start of in-lab study day to the end of the in-lab study day]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• University of Calgary — Calgary

Identifiers

NCT: NCT06751888 · REB24-1780

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗