Beta Blockers for Heat Stress

Overseen By Courtney Kirby, RN

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

Trial Summary

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 data supports the effectiveness of beta blockers like Metoprolol and Propranolol for heat stress?

While there is no direct evidence for using beta blockers like Metoprolol and Propranolol specifically for heat stress, these drugs are effective in managing conditions like high blood pressure and heart-related issues. They help by slowing down the heart rate and reducing the heart's workload, which might indirectly help the body handle stress better. ^{1 2 3 4 5}

Is it safe to use beta blockers like metoprolol and propranolol?

Research shows that metoprolol and propranolol are generally safe for humans, with mild side effects reported in some cases. In studies, these medications did not cause significant side effects related to therapy, and any side effects were usually mild and did not require stopping the treatment. ^{2 6 7 8 9}

How do the drugs Metoprolol and Propranolol help with heat stress?

Metoprolol and Propranolol are beta-blockers that may help manage heat stress by reducing heart rate and blood pressure, which can lower the body's stress response. Unlike other treatments, these drugs specifically target the heart's response to stress, potentially offering a unique approach to managing heat-related conditions. ^{2 7 10 11 12}

What is the purpose of this trial?

This study will test the hypothesis that the drugs propranolol and metoprolol will result in greater increases in core body temperature during 3 hours of extreme heat exposure in older adults.

Research Team

Craig Crandall, PhD

Principal Investigator

Univ of Texas Southwestern Med Ctr

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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 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 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]

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]

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]

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 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]

References

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

beta-Adrenoreceptor-blocking agents and lipid metabolism. [2019]

2. Sweden pubmed.ncbi.nlm.nih.gov

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

3. New Zealand 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. [2018]

4. England 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. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Atenolol in hypertension: follow-up of patients crossed over to this agent from propranolol, pindolol or metoprolol. [2013]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Evolution of oral drug forms of metoprolol: advantages of long acting modified release forms with modified release]. [2017]

7. Germany pubmed.ncbi.nlm.nih.gov

Comparative investigation on the cardio-protective action of the beta-blockers carazolol, propranolol and pindolol in rats. [2014]

8. Germany pubmed.ncbi.nlm.nih.gov

Double-blind, randomized, cross-over clinical trial of metoprolol and propranolol in mild to moderate essential hypertension. [2013]

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

Metoprolol versus thiazide diuretics in hypertension. Morbidity results from the MAPHY Study. [2019]

10. France pubmed.ncbi.nlm.nih.gov

Variability in the preventive action of the B-blockers on genetic hypertension in the rat. [2013]

11. Switzerland pubmed.ncbi.nlm.nih.gov

The effect of carazolol on the cardiovascular responses to adrenaline in stress sensitive pigs. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Reactivity to mental stress and cold provocation during long-term treatment with metoprolol, propranolol or hydrochlorothiazide. [2015]