Beta Blockers for Heat Stress

Overseen By Erin Harper, MS

Age: 65+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Cardiac drugs, Sweat inhibitors

Disqualifiers: Cancer, Diabetes, Neurological diseases, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 3 sessions of 3 hours each

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how two beta blockers, propranolol and metoprolol, affect body temperature during extreme heat. The goal is to determine if these drugs alter how older adults handle heat stress. Participants will receive various combinations of these drugs and a placebo (a harmless pill with no effect) to compare results. Healthy individuals over 65 with controlled cholesterol and blood pressure may be suitable for this trial. As a Phase 4 trial, this research involves FDA-approved treatments and aims to understand how they can benefit more patients.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any prescribed or over-the-counter medications that affect heart function or sweating, as these are not allowed in the trial.

What is the safety track record for these treatments?

Research shows that propranolol and metoprolol are generally safe for people, with studies indicating only mild side effects. In a clinical trial with 32 patients, metoprolol proved just as effective and safe as propranolol in lowering blood pressure. However, taking these medications in hot weather might increase the risk of heat-related problems. One study found that people on certain heart medications, like beta blockers, faced a higher risk of heart attacks during very hot weather. Thus, while these drugs are usually safe, extra care might be needed in extreme heat. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using beta blockers like Metoprolol and Propranolol for managing heat stress because they could offer a novel approach compared to current methods, which typically focus on cooling strategies and hydration. Unlike standard treatments, these beta blockers work by blocking the effects of adrenaline, potentially reducing the cardiovascular strain caused by heat. This unique mechanism could help protect the heart and reduce symptoms more effectively during heat stress episodes. If successful, these medications might provide a more targeted and efficient way to maintain heart health in high-temperature environments.

What evidence suggests that this trial's treatments could be effective for heat stress?

This trial will evaluate the effects of metoprolol and propranolol on managing heat stress. Studies have shown that both drugs can help manage heat stress by lowering heart rate and blood pressure, reducing the body's stress response in hot conditions. In a study with 32 patients, metoprolol proved as effective as propranolol in lowering blood pressure. Propranolol slowed the increase in heart rate that typically occurs when the body heats up. Both drugs are common beta-blockers with proven heart health benefits. These effects suggest they could help the body handle extreme heat better. Participants in this trial will receive different sequences of metoprolol, propranolol, and placebo to assess their effectiveness in managing heat stress. ^{3 6 7 8 9}

Who Is on the Research Team?

Craig Crandall, PhD

Principal Investigator

Univ of Texas Southwestern Med Ctr

Are You a Good Fit for This Trial?

This trial is for healthy older adults aged 65 and over with normal heart rhythms, cholesterol under 200 mg/dl, and blood pressure below 140/90 mmHg. Participants should not have significant medical issues.

Inclusion Criteria

My blood pressure is below 140/90 mmHg.

I am healthy with no major medical issues.

I am 65 years old or older.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive propranolol, metoprolol, and placebo during 3-hour heat exposure sessions

3 sessions of 3 hours each

3 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

• Metoprolol
• Propranolol

Trial Overview The study investigates how two heart medications, propranolol and metoprolol, affect the body's core temperature during extreme heat exposure for three hours in older individuals.

How Is the Trial Designed?

Group I: Propranolol, then Placebo, then Metoprolol Experimental Treatment 1 Intervention

Group II: Propranolol, then Metoprolol, then Placebo Experimental Treatment 1 Intervention

Group III: Placebo, then Propranolol, then Metoprolol Experimental Treatment 1 Intervention

Group IV: Placebo, then Metoprolol, then Propranolol Experimental Treatment 1 Intervention

Group V: Metoprolol, then Propranolol, then Placebo Experimental Treatment 1 Intervention

Group VI: Metoprolol, then Placebo, then Propranolol Experimental Treatment 1 Intervention

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

Approved in United States as Lopressor, Toprol XL for:

• Hypertension
• Acute Myocardial Infarction
• Congestive Heart Failure
• Angina

Approved in European Union as Lopressor, Toprol XL for:

• Hypertension
• Angina Pectoris
• Heart Failure
• Myocardial Infarction

Approved in Canada as Lopressor, Toprol XL for:

• Hypertension
• Angina
• Heart Failure
• Myocardial Infarction

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

In a clinical trial with 32 patients, metoprolol was found to be as effective and safe as propranolol in reducing both systolic and diastolic blood pressure in patients with mild to moderate essential hypertension.

While both medications had mild side effects, metoprolol did not cause central nervous system issues, and only two patients discontinued due to severe side effects, indicating a generally favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, randomized, cross-over clinical trial of metoprolol and propranolol in mild to moderate essential hypertension. Pandhi, P., Sahai, J., Wahi, PL., et al.[2013]

Combining chlorothiazide taken twice a day with various beta-blockers (atenolol, metoprolol, pindolol, and propranolol) effectively controlled blood pressure in patients with essential hypertension.

Each beta-blocker led to small but significant increases in plasma triglycerides and a decrease in fasting immuno-reactive glucagon levels, indicating potential metabolic effects alongside blood pressure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

beta-Adrenoreceptor-blocking agents and lipid metabolism. England, JD., Hua, AS., Shaw, J.[2019]

In a study on rats, the beta-blocker carazolol demonstrated superior cardio-protective effects against stress-induced heart damage, requiring significantly lower doses compared to pindolol and propranolol.

All three beta-blockers effectively prevented cardiac necrosis caused by isoprenaline, but carazolol provided almost complete protection, highlighting its potential as a more effective treatment in stress-related cardiac conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative investigation on the cardio-protective action of the beta-blockers carazolol, propranolol and pindolol in rats. Bartsch, W., Sponer, G., Dietmann, K., et al.[2014]

In a study of 45 essential hypertensive patients treated for 6 months, both beta-blockers (metoprolol and propranolol) and thiazide diuretics (hydrochlorothiazide) effectively lowered blood pressure, but beta-blockers were more effective in reducing heart rate and blood pressure during stress tests.

Beta-blockade significantly decreased heart rate reactivity to mental stress compared to thiazide diuretics, suggesting that beta-blockers may be a better option for managing blood pressure and cardiac workload in stressful situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reactivity to mental stress and cold provocation during long-term treatment with metoprolol, propranolol or hydrochlorothiazide. Eliasson, K., Kahan, T., Hylander, B., et al.[2015]

Metoprolol is an effective treatment for mild to moderate hypertension and angina pectoris, showing comparable efficacy to other medications like beta-blockers and diuretics, and can be administered in both twice-daily and once-daily doses.

While metoprolol has shown some benefits in reducing mortality in post-myocardial infarction patients over a longer term, its use during the acute phase of myocardial infarction remains controversial due to mixed results in mortality reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metoprolol. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in hypertension, ischaemic heart disease and related cardiovascular disorders. Benfield, P., Clissold, SP., Brogden, RN.[2018]

Propranolol, carazolol, and acebutolol effectively blocked the increase in heart rate and blood pressure caused by intravenous adrenaline in conscious Pietrain pigs, indicating their efficacy in managing adrenaline-induced cardiovascular responses.

The study suggests that while these non-cardioselective beta blockers can enhance vasopressor responsiveness, their use may carry potential complications when preventing stress-induced deaths in pigs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of carazolol on the cardiovascular responses to adrenaline in stress sensitive pigs. Gregory, NG., Wilkins, LJ.[2019]

In a study involving 23 hypertensive women, metoprolol (a selective beta-blocker) and propranolol (a non-selective beta-blocker) showed no significant differences in blood pressure, heart rate, body weight, or serum uric acid levels.

Both medications were well-tolerated, with no side effects related to the therapy observed in the participants, indicating their safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between metoprolol and propranolol as antihypertensive agents. A double-blind cross-over study. Bengtsson, C.[2019]

Metoprolol, particularly in its controlled release (CR/XL) form, has been shown to significantly lower mortality rates in patients with chronic heart failure compared to other forms, such as immediate release (IR) and sustained release (SR).

While metoprolol SR does not demonstrate superior antihypertensive efficacy compared to IR or CR/XL, the new controlled release formulation (CD/ERT) has been proven bioequivalent to CR/XL, suggesting it may offer similar benefits in managing heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evolution of oral drug forms of metoprolol: advantages of long acting modified release forms with modified release]. Leonova, MV., Maneshina, OA., Belousov, IuB.[2017]

In a study of young male SHR rats, beta-blockers propranolol and acebutolol effectively prevented hypertension not only during treatment but also for several weeks after stopping, indicating a lasting effect on blood pressure regulation.

Other beta-blockers like alprenolol and metoprolol were only effective during treatment, while oxprenolol showed no activity, highlighting that different beta-blockers have varying efficacy in preventing hypertension in SHR rats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variability in the preventive action of the B-blockers on genetic hypertension in the rat. de Clavière, M., Heyndrickx, JP., Brotelle, R., et al.[2013]

In a study of 3,234 hypertensive men aged 40-64, metoprolol significantly reduced the risk of coronary events compared to thiazide diuretics, with a relative risk of 0.76, indicating a 24% lower risk for those on metoprolol.

The study found no differences in blood pressure control or stroke rates between the two treatment groups, suggesting that the reduced risk of coronary events with metoprolol may be due to mechanisms beyond just lowering blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metoprolol versus thiazide diuretics in hypertension. Morbidity results from the MAPHY Study. Wikstrand, J., Warnold, I., Tuomilehto, J., et al.[2019]

A standardized method for objectively measuring performance in simulated car driving was developed, allowing for accurate assessment of driving abilities under different conditions.

In a study involving patients with untreated essential hypertension, both propranolol and metoprolol (beta-blockers) did not significantly affect driving performance compared to placebo, and the blood pressure response to stress remained unchanged after taking these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Objective measurement of performance during acute stress in patients with essential hypertension: assessment of the effects of propranolol and metoprolol. Dunn, FG., Lorimer, AR., Lawrie, TD.[2019]

In a study of 30 hypertensive patients, substituting atenolol for other beta-blockers (propranolol, pindolol, or metoprolol) led to better blood pressure control and fewer side effects over an average follow-up of 23.6 months.

Patients experienced a significant decrease in heart rate with atenolol, indicating its efficacy in managing hypertension while potentially simplifying their medication regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atenolol in hypertension: follow-up of patients crossed over to this agent from propranolol, pindolol or metoprolol. Frewin, DB., Penhall, RK., Leonello, PP., et al.[2013]

Citations

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Beta Blockers for Heat Stress In a clinical trial with 32 patients, metoprolol was found to be as effective and safe as propranolol in reducing both systolic and diastolic blood pressure in ...

2. fda.gov fda.gov/media/181809/download

Kaspargo Sprinkle Pediatric Postmarketing Safety Review This review focuses on United States (U.S.) serious unlabeled adverse events associated with metoprolol in pediatric patients. Kapspargo ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7327757/

Sprinkle formulations—A review of commercially available ... Currently, sixty-five original sprinkle drug products are available in various dosage forms including tablets, powders, granules, immediate-release capsules.

4. healio.com healio.com/clinical-guidance/drugs/kapspargo_sprinkle

Kapspargo Sprinkle: Uses, Side Effects & Dosage In healthy individuals, a maximum reduction in exercise-induced heart rate of approximately 10 and 15% occurs following IV administration of a single 5- and 15 ...

5. reference.medscape.com reference.medscape.com/drug/lopressor-toprol-xl-metoprolol-342360

Lopressor, Toprol XL, Kapspargo Sprinkle (metoprolol) ... Hypertension. Indicated for treatment of hypertension, to lower blood pressure. Lopressor. Tablet or oral solution: 100 mg/day PO initially in single dose ...

6. ysph.yale.edu ysph.yale.edu/news-article/two-heart-medications-tied-to-greater-heart-attack-risk-during-very-hot-weather/

Two Heart Medications Tied to Greater Heart Attack Risk ... People taking both drugs had a 75% higher risk. Non-users of those medications were not more likely to have a heart attack on hot days. Patients ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11541675/

The effect of prescription and over-the-counter medications ... Under heat stress, there was moderate quality evidence that drugs with high anticholinergic properties increased core temperature at air ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2009/019962s038lbl.pdf

TOPROL-XL - accessdata.fda.gov Signs and Symptoms​​ Overdosage of TOPROL-XL may lead to severe hypotension, sinus bradycardia, atrioventricular block, heart failure, cardiogenic shock, cardiac ...

9. singlecare.com singlecare.com/blog/medications-that-cause-heat-intolerance/

14 medications that make you sensitive to the heat Some meds increase dehydration and decrease sweat production. Check this list of medications that cause heat intolerance and stay safe this ...