Propranolol for Vascular Responses in Menopause

(2100208 Trial)

Overseen By Jacqueline Limberg

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: University of Missouri-Columbia

Must not be taking: Prescription medications

Disqualifiers: Pregnancy, Smoking, Diabetes, Cancer, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this study is to examine hypoxic vasodilation and the role of beta-adrenergic receptors in younger premenopausal, perimenopausal, and older postmenopausal women.

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.

Is propranolol generally safe for humans?

Propranolol has been studied in various forms and doses, showing that it is generally safe for humans with only minor side effects reported. Studies have shown no significant difference in side effects between different formulations, and no serious adverse effects were observed in healthy volunteers. ^{1 2 3 4 5}

What makes propranolol unique for treating menopause-related vascular responses?

Propranolol is unique because it is a nonselective beta-blocker that can affect the central nervous system to lower blood pressure by reducing sympathetic nervous activity, which may help manage menopause-related vascular responses. Its ability to influence the central nervous system and its wide range of uses, including anxiety and hypertension, make it distinct from other treatments. ^{2 6 7 8 9}

Eligibility Criteria

This trial is for women assigned female at birth who are premenopausal, perimenopausal, or postmenopausal. Participants should have a healthy weight with a BMI between 18 and 30 kg/m2. The study aims to understand how aging and menopause affect blood vessel responses during low oxygen conditions.

Inclusion Criteria

My BMI is between 18 and 30.

I was assigned female at birth.

I am before, during, or after menopause.

Exclusion Criteria

Body mass index >30 kg/m2

I do not have heart, liver, kidney, or lung disease.

Blood pressure ≥140/90 mmHg

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are exposed to hypoxia, hypercapnia, and cold pressor test to examine vascular responses

1-2 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Gemtesa (Medication)
• Placebo (Medication)
• Propranolol (Beta-blocker)

Trial Overview The study is testing the effects of Propranolol (a beta-blocker), Gemtesa (used for overactive bladder), and a placebo on blood vessel dilation in hypoxic conditions among different stages of menopause. It's designed to see if these drugs influence the body's response to low oxygen.

Participant Groups

Group I: Hypoxia Experimental Treatment 3 Interventions

Participants will be exposed to hypoxia (low oxygen air) using a mask.

Group II: Hypercapnia Experimental Treatment 3 Interventions

Participants will be exposed to hypercapnia (high carbon dioxide air) using a mask.

Group III: Cold pressor test Experimental Treatment 3 Interventions

Participants will be exposed to the cold pressor test (ice water on the foot).

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Findings from Research

In a study involving 51 patients, both long-acting formulations of propranolol significantly reduced the frequency of migraine attacks compared to placebo, demonstrating their efficacy in migraine management.

The higher dose formulation (Inderal LA 160 mg) was more effective than the lower dose (Half-Inderal LA 80 mg) in reducing migraine frequency, with no significant difference in side effects between the two formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting propranolol in the prophylaxis of migraine: a comparative study of two doses. Carroll, JD., Reidy, M., Savundra, PA., et al.[2017]

Propranolol, at lower doses of 40 and 80 mg, significantly impaired cognitive performance in tasks like simple reaction time and digital copying tests, indicating central effects on mental function.

Higher doses of propranolol (160 and 320 mg) showed reduced efficacy in impairing cognitive tasks and even worsened performance in some cases, suggesting that lower doses may be more effective for certain central effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Central effects of single oral doses of propranolol in man. Salem, SA., McDevitt, DG.[2019]

Inderectic, a combination of propranolol and bendrofluazide, significantly reduced blood pressure more effectively than either medication alone in a study of 21 hypertensive patients.

The study found that Inderectic was as effective as the same medications taken separately, with only minor side effects reported and no patients needing to withdraw from the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The fixed combination of propranolol and bendrofluazide in the treatment of hypertension. Jäättelä, A.[2013]

In two pharmacokinetic studies involving 48 healthy volunteers, newly formulated generic propranolol HCl tablets were found to have the same rate and extent of absorption as the brand Inderal tablets, indicating bioequivalence.

Both studies showed no statistically significant differences in key pharmacokinetic parameters (AUC, Cmax, tmax, and Cmin) between the test and reference tablets, confirming that the generic formulation is as effective as the branded version.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability of propranolol hydrochloride tablet formulations: application of multiple dose crossover studies. Eldon, MA., Kinkel, AW., Daniel, JE., et al.[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]

Propranolol lowers arterial pressure by decreasing sympathetic nervous activity, suggesting that its hypotensive effect involves action within the central nervous system (CNS).

The study indicates that this central action is related to beta-adrenoceptor blockade, as the dextro isomer of propranolol does not produce the same effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Central hypotensive effect of propranolol. Dollery, CT., Lewis, PJ.[2013]

In a study involving mature female Wistar rats, propranolol showed beneficial effects on the skeletal system regardless of the estrogen status, suggesting its potential as a treatment for bone health.

In vitro experiments indicated that while propranolol positively affects bone properties, it may have antagonistic interactions with estradiol, highlighting the complexity of its effects on bone metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do effects of propranolol on the skeletal system depend on the estrogen status? Sliwiński, L., Folwarczna, J., Pytlik, M., et al.[2020]

In a study of 110 patients with mild to moderate hypertension, Clinoril (sulindac) did not reduce the effectiveness of propranolol in lowering blood pressure, while piroxicam significantly increased diastolic blood pressure compared to both Clinoril and placebo.

Patients treated with piroxicam experienced a sustained increase in diastolic blood pressure, indicating that it may interfere with the antihypertensive effects of propranolol, unlike Clinoril which showed no such effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Clinoril (sulindac, MSD), piroxicam and placebo on the hypotensive effect of propranolol in patients with mild to moderate essential hypertension. Ebel, DL., Rhymer, AR., Stahl, E., 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. England pubmed.ncbi.nlm.nih.gov

Long-acting propranolol in the prophylaxis of migraine: a comparative study of two doses. [2017]

2. England pubmed.ncbi.nlm.nih.gov

Central effects of single oral doses of propranolol in man. [2019]

3. Finland pubmed.ncbi.nlm.nih.gov

The fixed combination of propranolol and bendrofluazide in the treatment of hypertension. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Bioavailability of propranolol hydrochloride tablet formulations: application of multiple dose crossover studies. [2019]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Central hypotensive effect of propranolol. [2013]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Do effects of propranolol on the skeletal system depend on the estrogen status? [2020]

8. Norway pubmed.ncbi.nlm.nih.gov

Effect of Clinoril (sulindac, MSD), piroxicam and placebo on the hypotensive effect of propranolol in patients with mild to moderate essential hypertension. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Propranolol. [2017]