Propranolol for Cardiovascular Disease

Overseen By Keely A Muscatell, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Prescription medications

Disqualifiers: Diabetes, Cardiovascular diseases, Mental illness, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

120 Participants Needed

Trial Summary

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 cardiovascular disease?

Research shows that long-acting propranolol (Inderal LA) is effective in treating conditions like angina (chest pain due to heart issues) and hypertension (high blood pressure), and it simplifies dosing, which can help patients stick to their treatment plan. Additionally, a combination of propranolol with another drug was more effective in lowering blood pressure than either drug alone. ^{1 2 3 4 5}

Is propranolol generally safe for humans?

Propranolol, a widely used beta-blocker for conditions like high blood pressure, has been associated with both serious and non-serious side effects, including bradycardia (slow heart rate). Long-acting formulations like Inderal LA are designed to provide a stable effect over 24 hours, which may help with patient convenience and compliance. ^{1 2 4 6 7}

How does the drug propranolol differ from other treatments for cardiovascular disease?

Propranolol, especially in its long-acting form (Inderal LA), is unique because it provides a steady release of the drug over 24 hours, reducing the need for multiple doses and potentially improving patient convenience and adherence. This formulation maintains stable blood levels and consistent effects, unlike conventional propranolol, which may have more variable peak concentrations. ^{1 2 4 6 7}

What is the purpose of this trial?

The purpose of this study is to map the neural and molecular mechanisms underlying psychological stress-induced changes in inflammation which could reveal new targets for intervention to reduce the risk of cardiovascular disease.

Research Team

Keely Muscatell, PhD

Principal Investigator

University of North Carolina, Chapel Hill

Eligibility Criteria

This trial is for right-handed, English-fluent individuals aged 18-30 with a BMI of 35 or less. It's not for those with certain physical illnesses like heart conditions, high blood pressure, diabetes, autoimmune diseases; metal implants; current prescription medication users; pregnant women; severe claustrophobics; or regular nicotine/drug users.

Inclusion Criteria

Right-handed

Fluent in English reading, writing, and speaking at least at a 10th grade level

Body mass index (BMI) less than or equal to 35 kg/m^2

Exclusion Criteria

I have a chronic condition like diabetes, heart disease, or an autoimmune disorder.

Assessed as screening, reassessed at Session I: Non-removeable metal devices/implants/objects in the body

I was told not to use over-the-counter meds on the day of Session II.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time oral dose of propranolol or placebo to examine the role of beta-adrenergic signaling in stress response

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in inflammatory gene expression and cytokine levels post-stress task

90 minutes

1 visit (in-person)

Treatment Details

Interventions

• Propranolol

Trial Overview The study investigates how the beta-blocker Propranolol affects stress-related inflammation and neural responses that could influence cardiovascular disease risk. Participants will be randomly given either Propranolol or a placebo to compare effects.

Participant Groups

Group I: Propranolol Experimental Treatment 1 Intervention

Propranolol tablet, 40mg, one-time, orally

Group II: Placebo Placebo Group 1 Intervention

Encapsulated placebo tablet

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

Approved in United States as Inderal for:

• High blood pressure
• Angina pectoris
• Heart rhythm disorders
• Migraine prophylaxis
• Essential tremor
• Performance anxiety

Approved in European Union as Propranolol for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Essential tremor
• Anxiety

Approved in Canada as Propranolol for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Essential tremor
• Anxiety

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

Dartmouth College

Collaborator

Trials

93

Recruited

1,415,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

A single dose of the long-acting formulation of propranolol (LA) resulted in a lower peak plasma level compared to the conventional formulation (CV), but LA maintained a more stable plasma level over time with a significantly longer elimination half-life (6.5 hours vs. 3.9 hours).

After 8 days of administration, LA showed accumulation in plasma levels, resulting in higher concentrations compared to CV, and the difference in heart rate suppression between the two formulations diminished by Day 8, indicating that LA may provide sustained effects over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics and pharmacological actions of a long-acting formulation of propranolol. Ohashi, K., Ebihara, A., Kondo, K., et al.[2013]

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]

Inderex, a combination of bendrofluazide and sustained-release propranolol, was found to be more effective in lowering blood pressure compared to either medication alone in a study of 21 patients.

The study indicated that there were no significant differences in treatment responses across different age groups, suggesting that Inderex is a suitable option for a wide range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of hypertension with a fixed ratio combination of long-acting propranolol and bendrofluazide, and influence of age of the subject. Herrick, AL., Davis, JM., Weir, RJ.[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]

In a study involving 12 patients with moderately severe angina pectoris, both conventional propranolol and Inderal L.A. showed similar therapeutic effectiveness in improving exercise tolerance, with no significant differences observed at various time points after dosing.

Patient compliance was high for both treatments, and no serious side effects were reported, indicating that both forms of propranolol are safe and well-accepted by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of propranolol and inderal L.A. in patients with angina. Scott, ME., Balnave, K.[2018]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics and pharmacological actions of a long-acting formulation of propranolol. [2013]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Treatment of hypertension with a fixed ratio combination of long-acting propranolol and bendrofluazide, and influence of age of the subject. [2013]

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

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

5. Northern Ireland pubmed.ncbi.nlm.nih.gov

Comparison of propranolol and inderal L.A. in patients with angina. [2018]

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

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

7. 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]