Controlled CO2 Inhalation for Neurogenic Orthostatic Hypotension

(CO2-nOH Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Calgary

Disqualifiers: Pregnancy, Heart failure, Pulmonary disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

28 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

How is the treatment Controlled CO2 Inhalation different from other treatments for neurogenic orthostatic hypotension?

Controlled CO2 Inhalation is unique because it involves inhaling carbon dioxide to potentially improve blood flow and blood pressure regulation, unlike other treatments that typically use medications to increase blood pressure. This approach may offer a non-drug alternative to manage symptoms without the risk of increasing blood pressure when lying down. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for individuals with neurogenic orthostatic hypotension (nOH), a condition causing blood pressure to drop when standing, leading to dizziness and fainting. Participants should have nOH symptoms and be able to undergo Head-up Tilt tests. Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

Ability to travel to Libin Cardiovascular Institute Autonomic Testing Lab at the University of Calgary, Calgary, AB.

I am either male or female.

I have been diagnosed with a condition that causes low blood pressure when standing.

Exclusion Criteria

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.

I cannot climb stairs without feeling short of breath due to heart or lung problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

In-lab Study Day

Participants undergo two Head-up Tilt (HUT) tests with different breathing protocols, one with and one without exogenous CO2 delivery. Heart rate, blood pressure, and breathing parameters are recorded.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the in-lab study day

2-4 weeks

Treatment Details

Interventions

• Controlled CO2 Inhalation

Trial Overview The study is testing the CarboHaler, a device that delivers controlled CO2, to see if it can improve blood pressure and reduce symptoms in nOH patients when they stand up. The effect of CO2 inhalation on systolic BP from lying down to standing will be measured.

Participant Groups

Group I: Controlled CO2 Inhalation Arm Experimental Treatment 1 Intervention

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.

Group II: 0% CO2 Arm Placebo Group 1 Intervention

In this arm, participants will breathe with the CO2 delivery device providing no exogenous CO2 while supine and during a 10-min HUT test.

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Findings from Research

A trial involving a healthy young volunteer demonstrated that induced syncope led to severe hyperventilation and periodic breathing, with hyperventilation rates reaching 57 L/min.

This hyperventilation caused a significant reduction in cerebral blood flow velocity by approximately 65%, highlighting the impact of respiratory changes on brain blood supply even without systemic hypotension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profound hyperventilation and development of periodic breathing during exceptional orthostatic stress in a 21-year-old man. Donnelly, J., Lucas, SJ., Thomas, KN., et al.[2011]

References

1. England pubmed.ncbi.nlm.nih.gov

Diagnosing and treating neurogenic orthostatic hypotension in primary care. [2015]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Profound hyperventilation and development of periodic breathing during exceptional orthostatic stress in a 21-year-old man. [2011]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and Durability of Effect with Long-Term, Open-Label Droxidopa Treatment in Patients with Symptomatic Neurogenic Orthostatic Hypotension (NOH303). [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Temporary elimination of orthostatic hypotension by norepinephrine infusion. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Management of Orthostatic Hypotension. [2020]