Propranolol for Cardiovascular Disease

Overseen By Jonathan Bunting, BS

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how propranolol, a medication, might reduce stress-related inflammation linked to cardiovascular disease. Researchers are testing whether this drug can target specific neural and molecular pathways affecting inflammation during stress. Participants will receive either propranolol or a placebo (a pill with no active drug) to compare outcomes. The trial is suitable for right-handed adults aged 18-30 who are fluent in English and have a BMI of 35 or lower, without existing health conditions like heart issues or diabetes. As a Phase 4 trial, propranolol is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

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 is the safety track record for Propranolol?

Research has shown that propranolol is generally safe for people. The FDA has approved it for treating conditions like high blood pressure, chest pain, and heart rhythm problems, providing extensive information about its effects. Common side effects include a slower heart rate and low blood pressure, and consulting a doctor is important if these occur. In rare cases, propranolol can worsen heart problems or cause fluid buildup, especially in those with existing heart issues. Overall, propranolol is well-researched and usually effective for most people. However, like any medicine, it can have side effects, so monitoring one's condition while taking it is crucial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for cardiovascular disease focus on managing symptoms and reducing risk factors, often through medications like statins, ACE inhibitors, or beta-blockers. However, propranolol stands out because it specifically targets beta-adrenergic receptors, helping to reduce heart rate and blood pressure more directly. Researchers are excited about propranolol because it has the potential to offer quick relief with a single 40mg oral dose, which is a convenient option compared to other medications that may require long-term use or higher dosages. By acting on these receptors, propranolol can provide a more targeted approach to improving heart function and potentially enhance patient outcomes.

What is the effectiveness track record for Propranolol in treating cardiovascular disease?

Research shows that propranolol, which participants in this trial may receive, effectively manages high blood pressure, a major factor in heart disease. Studies have found that it can lower the systolic blood pressure by about 9 points and the diastolic pressure by about 6.6 points. Propranolol also slows the heart rate, reducing stress on the heart. As a beta blocker, it helps the heart beat more slowly and with less force. This makes propranolol a proven treatment for managing conditions that lead to heart disease. ^{6 7 8 9 10}

Who Is on the Research Team?

Keely Muscatell, PhD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8109325/

Comparison of a Chronotherapeutically Administered β ... Treatment with Innopran XL resulted in significant decreases in mean 24‐hour SBP (−9.0±12.2 mm Hg; p<0.0001) and DBP (−6.6±8.4 mm Hg; p<0.0001) from baseline ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8109330/

The Antihypertensive Efficacy and Safety of a ... Propranolol CR significantly reduced mean morning heart rate in all groups compared with placebo (Figure 3). Similar significant decreases were seen when heart ...

3. drugs.com drugs.com/compare/inderal-vs-innopran-xl

Inderal vs InnoPran XL Comparison Inderal has an average rating of 7.6 out of 10 from a total of 74 ratings on Drugs.com. 70% of reviewers reported a positive effect, while 19% reported a ...

4. reference.medscape.com reference.medscape.com/drug/inderal-inderal-la-propranolol-342364

Inderal, Inderal LA (propranolol) dosing, indications, ... Indicated for management of hypertension. Immediate release: 40 mg PO q12hr initially, increasing every 3-7 days; maintenance: 80-240 mg PO q8-12hr; not to ...

5. mayoclinic.org mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/beta-blockers/art-20044522

Beta blockers Beta blockers are medicines that lower blood pressure. They also may be called beta-adrenergic blocking agents.

6. medicalnewstoday.com medicalnewstoday.com/articles/drugs-inderal

Inderal LA and Inderal XL: Side effects, uses, dosage, and ... It's possible for Inderal LA or Inderal XL to cause a slowed heart rate, which may also be called bradycardia. This was a common side effect of both medications ...

7. drugs.com drugs.com/propranolol.html

Propranolol: Uses, Dosage, Side Effects, Warnings Propranolol is used to treat tremors, angina (chest pain), hypertension (high blood pressure), heart rhythm disorders, and other heart or circulatory ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2008/021438s011lbl.pdf

InnoPran XL®(propranolol hydrochloride) Extended Release ... Blood levels and/or toxicity of propranolol may be increased by administration of InnoPran XL with substrates or inhibitors of CYP2C19, such as fluconazole, ...

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Propranolol (oral route) - Side effects & dosage This medicine may increase the risk of heart or blood vessel problems (eg, bradycardia, hypotension). Check with your doctor right away if your ...

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Propranolol (Inderal LA, Innopran XL, others) - Uses, Side ... Propranolol may worsen existing heart failure or cause fluid buildup in your body. For individuals with underlying heart disease or heart damage ...