Carbon Dioxide Breathing for Orthostatic Hypotension

Overseen By Rasha Hamzeh, RN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Calgary

Must not be taking: Autonomic drugs

Disqualifiers: Somatization, Severe anxiety, Pregnancy, others

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

Compensation: Varies

Number of Visits: 5

Duration: 5 sessions

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist people with Neurogenic Orthostatic Hypotension (NOH), a condition where blood pressure drops significantly upon standing, causing dizziness and fainting. Researchers are testing whether inhaling small amounts of extra carbon dioxide, known as Sequential Gas Delivery, can raise blood pressure and improve symptoms. Participants will try different carbon dioxide levels while standing to determine the most effective dose. This approach could offer a new therapy for those who often feel light-headed when standing. Individuals with NOH who can travel to the University of Calgary for the study might be suitable candidates. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for NOH.

Will I have to stop taking my current medications?

The trial excludes participants taking medications that could interfere with autonomic function testing, so you may need to stop certain medications. It's best to discuss your specific medications with the trial team to see if they are allowed.

What prior data suggests that this method is safe for treating orthostatic hypotension?

Research has shown that inhaling a small amount of extra carbon dioxide can help increase blood pressure when standing. This may benefit individuals with neurogenic orthostatic hypotension (NOH), a condition where blood pressure drops excessively upon standing. Studies have found that this method can reduce symptoms like light-headedness or fainting.

For healthy volunteers, inhaling a bit more carbon dioxide is generally safe and helps control blood pressure. Most people tolerate the treatment well, experiencing no serious side effects. However, as with any treatment, individual reactions may vary.

Overall, using carbon dioxide in this way appears promising as a new treatment for managing NOH. Participants should discuss any concerns with the study team to understand what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Orthostatic hypotension often relies on medications like fludrocortisone and midodrine, which work by increasing blood volume or tightening blood vessels. Researchers are excited about the carbon dioxide breathing technique because it offers a new approach by stabilizing or increasing carbon dioxide levels in the blood. This method could potentially improve blood flow and pressure without the side effects associated with current drugs. By exploring various CO2 levels and combinations with oxygen, this trial aims to find out if this could be a safer, more effective way to manage symptoms of orthostatic hypotension.

What evidence suggests that this trial's treatments could be effective for orthostatic hypotension?

Research has shown that slightly increasing carbon dioxide intake can help with Neurogenic Orthostatic Hypotension (NOH). In earlier studies, small increases in carbon dioxide levels raised blood pressure in healthy individuals when they stood up, reducing symptoms like light-headedness. The concept is that more carbon dioxide stimulates the part of the nervous system that regulates blood pressure and blood flow to the brain. This trial will explore various levels of carbon dioxide exposure, including +0mmHg CO2 clamped at baseline, +5mmHg CO2, +10mmHg CO2, and +10mmHg CO2 combined with 50mmHg O2, to assess their effectiveness in stabilizing blood pressure and reducing symptoms when standing. This new approach could be promising for those dealing with NOH. ^{1 2 3 4 6}

Who Is on the Research Team?

Satish R Raj, MD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

This trial is for adults over 18 who can consent, travel to the University of Calgary, and are non-smokers. It's not for those with dementia, substance abuse issues, severe organ diseases, pregnant or breastfeeding women, people on certain medications affecting autonomic function or unable to wear a mask.

Inclusion Criteria

Able and willing to provide informed consent

I am either male or female.

People who do not smoke.

Exclusion Criteria

You have severe anxiety or somatization symptoms.

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

I need portable oxygen for breathing, either at rest or during physical activity.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo Active Stand Tests with varying levels of CO2 and O2 to evaluate the effects on blood pressure and orthostatic tolerance

5 sessions

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sequential Gas Delivery

Trial Overview The study tests if breathing in higher levels of carbon dioxide (Sequential Gas Delivery) can help manage low blood pressure when standing in patients with Neurogenic Orthostatic Hypotension by increasing blood pressure and brain blood flow.

How Is the Trial Designed?

Group I: +5mmHg CO2 Experimental Treatment 1 Intervention

All participants will complete an active stand breathing +5mmHg of CO2 relative to baseline

Group II: +10mmHg CO2 + 50mmHg O2 Experimental Treatment 1 Intervention

All participants will complete an active stand breathing +10mmHg of CO2 relative to baseline and 50mmHg of O2

Group III: +10mmHg Experimental Treatment 1 Intervention

All participants will complete an active stand breathing +10mmHg of CO2 relative to baseline

Group IV: +0mmHg CO2 Clamped at baseline Experimental Treatment 1 Intervention

All participants will complete an active stand with their CO2 held constant at baseline

Group V: Room Air Active Control 1 Intervention

All participants will complete an active stand breathing room air with CO2 free to fluctuate

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Published Research Related to This Trial

Oxygen therapy should start with the minimum effective dose, with initial FiO2 levels ranging from 24% to 100% based on the patient's condition, particularly in cases of COPD exacerbations and chronic hypercapnia.

High FiO2 levels can be safely administered for limited durations, with guidelines suggesting that 100% oxygen is safe for less than six hours, while 70% can be used for up to 24 hours, and 45% should be the upper limit for longer durations to prevent oxygen toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen therapy and oxygen toxicity. Tinits, P.[2022]

In a study of 24 hypoxaemic patients with acute exacerbations of COPD, only 3 patients experienced clinically significant CO2 retention while receiving controlled oxygen therapy, indicating a low risk of worsening hypercapnia with this treatment.

The patients who did develop CO2 retention had more severe hypercapnia but still required only low-flow oxygen, suggesting that controlled oxygen therapy can be safely administered to most COPD patients with careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled oxygen therapy and carbon dioxide retention during exacerbations of chronic obstructive pulmonary disease. Moloney, ED., Kiely, JL., McNicholas, WT.[2015]

Long-term oxygen therapy is beneficial for patients with chronic obstructive lung disease (COPD), improving their quality of life and survival rates, but it requires careful patient selection due to its complexity and cost.

The article discusses the necessary tests and criteria for prescribing long-term oxygen therapy, highlighting advancements in delivery methods, particularly the use of transtracheal catheters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ambulatory long-term oxygen therapy]. Michel, F., Perruchoud, AP.[2016]

A new comprehensive approach to managing altitude mountain sickness (AMS) includes the use of hyperbaric oxygenation (HBO2) therapy, which can effectively treat hypoxaemia by providing oxygen under high pressure, potentially reducing AMS symptoms more effectively than traditional methods.

This method utilizes advanced hyperbaric treatment profiles developed for military and NASA applications, which can prevent AMS rebound effects that often occur with standard treatments, especially in elderly populations who may not tolerate conventional therapies well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altitude mountain sickness among tourist populations: a review and pathophysiology supporting management with hyperbaric oxygen. Butler, GJ., Al-Waili, N., Passano, DV., et al.[2011]

A quality improvement pilot study showed that implementing a structured protocol for oxygen therapy significantly increased the proportion of patients with a prescribed target oxygen saturation range from 85% to 95%.

The improvement in oxygen target range prescribing was sustained at 96% even 12 months after the protocol was introduced, indicating effective long-term practice change in critical care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementing target range oxygen in critical care: A quality improvement pilot study. Heartshorne, R., Cardell, J., O'Driscoll, R., et al.[2022]

In a study of 12 patients with chronic lung disease, most retained their ability to respond to carbon dioxide levels during sleep, suggesting that oxygen therapy is generally safe for these patients.

While some patients experienced a significant increase in carbon dioxide levels with oxygen therapy, the majority showed only a minor increase, indicating that careful monitoring can help manage oxygen therapy effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of oxygen administration during sleep on skin surface oxygen and carbon dioxide tensions in patients with chronic lung disease. Hazinski, TA., Hansen, TN., Simon, JA., et al.[2013]

Intermittent negative pressure ventilation (INPV) combined with increasing oxygen concentrations was tested on 17 male patients with severe COPD, successfully raising arterial oxygen levels without worsening carbon dioxide retention.

This method not only improved oxygen levels significantly (from 47.2 mm Hg to 61.5 mm Hg) but also reduced carbon dioxide levels (from 74.4 mm Hg to 65.6 mm Hg), suggesting it could be a safer alternative to intubation and mechanical ventilation for patients with severe respiratory failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent short-term negative pressure ventilation and increased oxygenation in COPD patients with severe hypercapnic respiratory failure. Sauret, JM., Guitart, AC., Rodríguez-Froján, G., et al.[2019]

Oxygen is a crucial life-saving treatment for patients with severe hypoxemia, but its use has often been based on tradition rather than scientific evidence, leading to potential risks.

Excessive oxygen therapy can increase mortality rates in critically ill patients, even in those without conditions like COPD that predispose them to carbon dioxide retention, highlighting the need for more careful management of oxygen administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen Use in Critical Illness. O'Driscoll, BR., Smith, R.[2020]

The article emphasizes the importance of nurses understanding the safe administration of oxygen therapy, particularly for patients with chronic obstructive pulmonary disease (COPD) and type II respiratory failure.

It highlights potential complications that can arise from oxygen delivery in these patients, underscoring the need for careful monitoring and management during acute care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of oxygen therapy. McGloin, S.[2008]

Citations

1. withpower.com withpower.com/trial/carbon-dioxide-breathing-for-orthostatic-hypotension-6fe05

Carbon Dioxide Breathing for Orthostatic Hypotension This method not only improved oxygen levels significantly (from 47.2 mm Hg to 61.5 mm Hg) but also reduced carbon dioxide levels (from 74.4 mm Hg to 65.6 mm Hg) ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05295810

NCT05295810 | Hypercapnia in Orthostatic Hypotension In healthy volunteers, small increases in the amount of inhaled carbon dioxide has been shown to increase BP in the upright position, and this improves symptoms ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11973564/

Carbon dioxide for neurogenic orthostatic hypotension in ... In this proof-of-concept study, we tested the hypothesis that increased inspired CO 2 increases standing blood pressure in patients with nOH.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2452302X24001840

Clinical Reduced Stroke Volume and Brain Perfusion Drive ... This study challenges current hypotheses by revealing that exaggerated peripheral chemoreceptor activity is not the primary driver of postural hyperventilation.

5. centerwatch.com centerwatch.com/clinical-trials/listings/condition/575/orthostatic-hypotension

Orthostatic Hypotension Clinical Research Trials Orthostatic hypotension is a condition where a person's blood pressure drops significantly when they stand up from a sitting or lying position.

6. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1600772/full

Mild intermittent hypoxia may improve autonomic ... Systolic autonomic dysreflexia improved by 46% ± 14% and orthostatic hypotension improved by 160% ± 63% after MIH. ... carbon dioxide (Hans Rudolph Inc., SmartLab ...