Propranolol for Hypoxia

Overseen By Jacqueline K Limberg, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Missouri-Columbia

Must not be taking: Hormonal contraceptives, Prescription medications

Disqualifiers: Sleep apnea, Cardiovascular, Diabetes, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

35 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this project is to identify sex-related differences in the effect of hypoxia on sympathetic vascular transduction.

Will I have to stop taking my current medications?

Yes, you will need to stop taking your current prescription medications to participate in this trial.

What data supports the effectiveness of the drug propranolol for hypoxia?

Propranolol is known to be effective in treating conditions like hypertension (high blood pressure) and angina pectoris (chest pain due to heart issues), as it helps to block certain receptors in the heart and blood vessels, leading to reduced heart rate and blood pressure. However, there is no direct evidence from the provided research that supports its effectiveness specifically for hypoxia (low oxygen levels in the body). ^{1 2 3 4 5}

Is propranolol generally safe for humans?

Propranolol has been used for many years to treat conditions like high blood pressure and heart issues, and while it can cause some side effects, serious adverse effects are uncommon. In studies, it has been shown to reduce sudden cardiac deaths in high-risk patients, and long-acting formulations have been developed to maintain stable effects. However, toxic doses can lead to serious issues like respiratory failure, especially in animal studies. ^{3 6 7 8 9}

How does the drug propranolol differ from other treatments for hypoxia?

Propranolol is unique because it is a beta-blocker that can also cause direct vasodilation (widening of blood vessels), which may be beneficial in treating hypoxia (low oxygen levels in the body). Unlike other treatments, it has been studied for its effects on the liver's ability to clear the drug under hypoxic conditions, suggesting a novel approach to managing hypoxia. ^{1 3 6 10 11}

Research Team

Jacqueline K Limberg, Ph.D.

Principal Investigator

University of Missouri-Columbia

Eligibility Criteria

This trial is for healthy adults, both men and women aged between 18-45 with a BMI of 18-30. Participants must not be pregnant, breastfeeding, or using nicotine products. Those with high blood pressure, nerve diseases, diabetes, PCOS, drug use issues, recent COVID-19 symptoms, sleep apnea or major organ diseases are excluded.

Inclusion Criteria

Your body mass index (BMI) is between 18 and 30.

Non-pregnant and non-breastfeeding

You do not use nicotine.

Exclusion Criteria

I have recently been diagnosed with COVID-19 and am showing symptoms.

Your blood pressure is higher than 140/90 mmHg.

I have a nerve or neurological condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Hypoxia Exposure

Men and women will be exposed to isocapnic hypoxia. Participants will wear a mask and systemic oxygen levels will be titrated to attain hypoxemia as assessed by pulse oximetry.

1 session

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• Normal Saline
• Placebo
• Propranolol Hydrochloride

Trial Overview The study aims to understand how low oxygen levels affect blood vessel responses differently in men and women by comparing the effects of a Propranolol pill (a beta-blocker) versus a placebo (inactive pill).

Participant Groups

Group I: Hypoxia Exposure Experimental Treatment 2 Interventions

Men and women will be exposed to isocapnic hypoxia. Participants will wear a mask and systemic oxygen levels will be titrated to attain hypoxemia as assessed by pulse oximetry.

Propranolol Hydrochloride is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Inderal for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Performance anxiety

Approved in European Union as Inderal for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Performance anxiety

Approved in Canada as Inderal for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Performance anxiety

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

Findings from Research

In a single-blind study involving 13 patients with mild to moderately severe hypertension, the combination of propranolol (80 mg) and bendrofluazide (2.5 mg) effectively controlled blood pressure in 12 patients over a 12-week period.

The treatment did not result in significant changes in biochemical parameters or ECG readings, and no serious side effects were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixed ratio combination of propranolol and bendrofluazide in the treatment of hypertension. Pandhi, P., Sharma, BK., Sharma, PL., et al.[2013]

Long-acting propranolol (Inderal LA) provides a controlled release of the medication, maintaining higher plasma concentrations over 24 hours compared to conventional tablets, which helps ensure consistent beta-adrenoceptor blockade.

This formulation is equally effective for treating conditions like angina pectoris, hypertension, and hyperthyroidism, while potentially improving patient adherence to treatment due to simplified dosing regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting propranolol (Inderal LA): pharmacokinetics, pharmacodynamics and therapeutic use. Mishriki, AA., Weidler, DJ.[2019]

A study involving six healthy adult volunteers tested four different brands of propranolol (Inderal, Ciplar, Corbeta, and Propal) to assess variations in how the body absorbs and responds to the medication.

The results showed no significant differences in the pharmacokinetic (how the drug is processed in the body) and pharmacodynamic (the drug's effects on the body) parameters among the brands, indicating they are likely interchangeable in terms of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers. Biswas, NR., Garg, SK., Kumar, N., et al.[2013]

The study analyzed data from the Canadian Adverse Drug Reaction Monitoring Program to assess the potential link between propranolol hydrochloride and bradycardia, finding that the signals for bradycardia were not statistically significant despite some high calculated statistics.

Although the results did not confirm a strong association between propranolol and bradycardia, the authors suggest that further investigation using larger databases is warranted due to the observed trends.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic class-specific signal detection of bradycardia associated with propranolol hydrochloride. Gavali, DK., Kulkarni, KS., Kumar, A., et al.[2021]

Controlled-release formulations of propranolol, specifically Elanol and Inderal LA, provide smoother serum level profiles and delayed peak times compared to conventional propranolol, indicating a potentially more stable therapeutic effect.

Elanol showed greater bioavailability than Inderal LA, suggesting that long-acting formulations can be effective without the drawbacks of reduced bioavailability due to first-pass metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic studies with a new controlled-release formulation of propranolol in normal volunteers: a comparison with other commercially available formulations. Perucca, E., Grimaldi, R., Gatti, G., et al.[2019]

Propranolol is a versatile noncardioselective β-blocker used to treat various conditions, including hypertension, anxiety disorders, and migraine prophylaxis, highlighting its efficacy in managing both cardiovascular and non-cardiovascular symptoms.

The study provides a comprehensive profile of propranolol, detailing its physicochemical properties and pharmacological actions, which are essential for understanding its therapeutic uses and potential interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol. Al-Majed, AA., Bakheit, AHH., Abdel Aziz, HA., et al.[2017]

References

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

A fatal case of propranolol poisoning. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Fixed ratio combination of propranolol and bendrofluazide in the treatment of hypertension. [2013]

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

Ring-hydroxylated propranolol: synthesis and beta-receptor antagonist and vasodilating activities of the seven isomers. [2019]

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

Long-acting propranolol (Inderal LA): pharmacokinetics, pharmacodynamics and therapeutic use. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers. [2013]

6. India pubmed.ncbi.nlm.nih.gov

Therapeutic class-specific signal detection of bradycardia associated with propranolol hydrochloride. [2021]

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

Beta blockade after myocardial infarction: the Norwegian propranolol study in high-risk patients. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic studies with a new controlled-release formulation of propranolol in normal volunteers: a comparison with other commercially available formulations. [2019]

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

Toxic doses of rac-, (-)-(S)- and (+)-(R)-propranolol in rats and rabbits. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Propranolol. [2017]

11. England pubmed.ncbi.nlm.nih.gov

The effect of hypoxia and acidosis on propranolol clearance in the isolated perfused rat liver preparation. [2019]