Caffeine for Cardiovascular Disease

Not yet recruiting at 2 trial locations

Overseen By Luca Malatesta

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Hamilton Health Sciences Corporation

Must not be taking: Caffeine-interacting medications

Disqualifiers: Pregnancy, Diabetes, Hypertension, Heart disease, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how caffeine, a common stimulant, affects certain blood markers potentially linked to heart disease. Participants will take either caffeine pills or placebo pills, with multiple blood tests conducted to compare results. The study also evaluates the ease of recruiting and retaining participants and whether the study steps can be applied in a larger trial later. Individuals in good health who can fast overnight are well-suited for this study. As an Early Phase 1 trial, this research aims to understand how caffeine affects the body, offering participants a chance to contribute to foundational scientific knowledge.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that individuals taking medication that may have adverse interactions with caffeine will be excluded. It's best to discuss your current medications with the trial investigators to see if they might interfere.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that caffeine is one of the most studied substances regarding its effects on the heart. Some studies suggest caffeine might increase the risk of heart problems, while others show no effect. This ongoing debate highlights uncertainty about caffeine's impact on heart health.

In this trial, participants will take 400 mg of caffeine in pill form, equivalent to about four cups of coffee. Some research suggests that consuming more than 400 mg of caffeine daily could raise the risk of heart disease in healthy people. However, drinking one to three cups of coffee a day might actually lower the risk of dying from heart problems.

Since this trial is in its early phase, it primarily focuses on assessing the feasibility of the procedures and participants' responses. While this does not strongly prove safety, caffeine is widely consumed, and many people tolerate it well. The trial aims to gather more specific data about caffeine's effects on blood markers related to heart disease. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using caffeine as a treatment for cardiovascular disease because it represents a novel approach compared to standard options like statins or beta-blockers, which primarily target cholesterol levels or blood pressure. Caffeine is a natural stimulant known for its ability to increase heart rate and improve circulation, potentially offering new benefits for heart health. Additionally, its widespread availability and well-understood safety profile make it an attractive candidate for exploring new therapeutic uses. This trial could reveal whether caffeine's unique effects on the cardiovascular system could be harnessed effectively for disease management.

What evidence suggests that this trial's treatments could be effective for cardiovascular disease?

Research suggests that caffeine might benefit heart health. Some studies have found that people who drink more coffee may have a lower risk of heart issues, such as irregular heartbeats and heart failure. Caffeine does not link to a higher risk of heart disease, and moderate amounts usually don't raise blood pressure. It might also help protect the heart and boost physical performance. While these findings are encouraging, more research is needed to fully understand caffeine's effects on heart health. This trial will further investigate caffeine's impact on cardiovascular health, with participants in different groups receiving either caffeine or a placebo to compare outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

Guillaume Pare, MD

Principal Investigator

Population Health Research Institute

Are You a Good Fit for This Trial?

This trial is for people with or without cardiovascular disease who are interested in how caffeine affects their body. Participants must be willing to fast overnight, take a caffeine pill or placebo, and have blood samples taken using different methods. They should not have conditions that exclude them from the study.

Inclusion Criteria

I am over 18 years old.

Exclusion Criteria

Individuals who experience anxiety or have been diagnosed with other mental illnesses will want to consider their participation in this study.

Individuals who are diabetic will be excluded from this study due to the fasting period, potentially leading to a low blood sugar state.

I do not have hypertension, glaucoma, thyroid disease, heart disease, or a history of seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 - Preliminary Testing

Participants undergo blood collection by intravenous sampling, TASSO+ device, and finger prick. They ingest caffeine or placebo and have blood collected at 3 and 6 hours post-ingestion.

1 day

1 visit (in-person)

Phase 2 - At-home Testing

Participants self-collect blood using the TASSO+ device at home, ingest caffeine or placebo, and collect blood at 3 and 6 hours post-ingestion.

1 day

Remote participation

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Caffeine

Trial Overview The trial tests the effects of a 400mg caffeine pill on blood biomarkers related to cardiovascular health versus a placebo. It also evaluates participant adherence and compares capillary blood sampling (using TASSO+ device and Whatman cards) with traditional venous sampling.

How Is the Trial Designed?

Group I: Caffeine - Phase 2 Experimental Treatment 2 Interventions

The sample size of this arm is 13 participants. In this arm, participants will remain at home to complete study procedures. They will undergo an overnight fast of at least 8 hours, then self-collect blood using the TASSO+ device. They will then ingest a 400mg dose of caffeine and remain fasted for the following 6 hours. At 3 hours and 6 hours post caffeine consumption, participants will collect their blood using the TASSO+ device.

Group II: Caffeine - Phase 1 Experimental Treatment 4 Interventions

The sample size of this arm is 5 participants. In this arm, participants will have to come to the Population Health Research Institute building to complete study procedures. They will undergo an overnight fast of at least 8 hours, then undergo blood collection by intravenous sampling, as well as by the TASSO+ device and finger prick and collection on Whatman Protein 903 Saver Cards. They will then ingest a 400mg dose of caffeine and remain fasted for the following 6 hours. At 3 hours and 6 hours post caffeine consumption, participants will have their blood collected in the same manner as the initial blood collection.

Group III: Control - Phase 2 Placebo Group 2 Interventions

The sample size of this arm is 13 participants. In this arm, participants will remain at home to complete study procedures. They will undergo an overnight fast of at least 8 hours, then self-collect blood using the TASSO+ device. They will then ingest 2 placebo pills and remain fasted for the following 6 hours. At 3 hours and 6 hours post caffeine consumption, participants will collect their blood using the TASSO+ device.

Group IV: Control - Phase 1 Placebo Group 4 Interventions

The sample size of this arm is 5 participants. In this arm, participants will have to come to the Population Health Research Institute building to complete study procedures. They will undergo an overnight fast of at least 8 hours, then undergo blood collection by intravenous sampling, as well as by the TASSO+ device and finger prick and collection on Whatman Protein 903 Saver Cards. They will then ingest 2 placebo pills and remain fasted for the following 6 hours. At 3 hours and 6 hours post caffeine consumption, participants will have their blood collected in the same manner as the initial blood collection.

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

Approved in United States as Caffeine for:

• Restoring mental alertness or wakefulness during fatigue or drowsiness
• Short-term treatment of neonatal apnea (breathing problems)
• Headache and migraine relief
• Weight loss

Approved in Canada as Caffeine for:

• Restoring mental alertness or wakefulness during fatigue or drowsiness
• Short-term treatment of neonatal apnea (breathing problems)
• Headache and migraine relief

Approved in European Union as Caffeine for:

• Restoring mental alertness or wakefulness during fatigue or drowsiness
• Short-term treatment of neonatal apnea (breathing problems)
• Headache and migraine relief

Who Is Running the Clinical Trial?

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Recruited

345,000+

Published Research Related to This Trial

A multicenter, double-blind, placebo-controlled trial was conducted to evaluate the effectiveness and safety of combining ibuprofen with caffeine for treating tension-type headaches, building on previous evidence of caffeine's analgesic properties.

The study aims to confirm the pain-relieving effects of caffeine and explore how tension-type headaches can serve as a useful model for pain research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of ibuprofen plus caffeine to treat tension-type headache. Diamond, S., Freitag, FG.[2019]

In two large-scale studies involving over 55,000 patients, etodolac demonstrated significant efficacy in reducing pain associated with rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis, with pain improvements of 33% to 50% depending on the condition.

The safety profile of etodolac was found to be very acceptable, with only 11% of patients reporting adverse reactions, and severe reactions being rare, confirming its favorable risk/benefit ratio compared to other NSAIDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large-scale open trials with etodolac (Lodine) in France: an assessment of safety. Benhamou, CL.[2019]

In a 91-day study involving 307 participants with osteoarthritis pain inadequately controlled by COX-2 NSAIDs, the combination of tramadol 37.5 mg and acetaminophen 325 mg significantly reduced pain compared to placebo, with a final VAS score of 41.5 versus 48.3 (p = 0.025).

The tramadol/APAP combination also improved overall medication assessments and quality of life measures, while the most common side effects were mild, including somnolence (6.5%) and nausea (4.6%), indicating it is a safe and effective add-on therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tramadol/acetaminophen tablets (Ultracet) as add-on therapy for osteoarthritis pain in subjects receiving a COX-2 nonsteroidal antiinflammatory drug: a multicenter, randomized, double-blind, placebo-controlled trial. Emkey, R., Rosenthal, N., Wu, SC., et al.[2015]

In phase 3 trials, sumatriptan/naproxen sodium (Treximet®) was found to be significantly more effective than placebo in providing pain relief for migraines in both adolescents and adults, with a notable increase in the number of patients who were pain-free at 2 hours after treatment.

The combination medication was generally well tolerated, with low rates of treatment-related adverse events (≤11% in adolescents and ≤22% in adults), making it a safe and effective option for acute migraine treatment that may also enhance patient adherence due to its fixed-dose formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sumatriptan/Naproxen Sodium: A Review in Migraine. Syed, YY.[2018]

Etodolac, a new NSAID, has an excellent safety profile, with gastrointestinal disturbances being the most common side effects, but the rates of serious issues like gastrointestinal ulceration are very low (less than 0.3%).

The review included data from 3,302 patients in clinical trials and 8,334 in post-marketing studies, showing that elderly patients do not have a higher risk of adverse effects compared to the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An updated safety profile of etodolac in several thousand patients. Schattenkirchner, M.[2013]

In a study involving 60 young, healthy volunteers, tramadol, dextropropoxyphene, and a commercial drug mixture all significantly increased pain thresholds in dental pulp, indicating their analgesic efficacy.

There was no significant difference in the pain-relieving effects among the three drugs, suggesting that they may be equally effective for managing pain in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of tramadol and other analgesics on the pain threshold in human dental pulp (author's transl)]. Rost, A., Schenck, EG.[2006]

In a 3-month study involving 3066 stable angina patients, trimetazidine (TMZ) 80 mg once daily significantly reduced the frequency of angina attacks from an average of 4.7 to 0.9 per week and decreased the use of short-acting nitrates from 4.5 to 0.7 per week.

The treatment also improved patient adherence to medication from 24% to 56%, with high satisfaction ratings (9.5 out of 10), indicating that the once-daily formulation of TMZ is effective and well-tolerated in managing chronic stable angina.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Anginal Effectiveness and Tolerability of Trimetazidine Modified Release 80 Mg Once Daily in Stable Angina Patients in Real-World Practice. Glezer, MG., Vygodin, VA.[2022]

The combination of paracetamol (1,000 mg) and caffeine (130 mg) (PCF) was found to be well-tolerated and effective for treating tension-type headache (TTH) in an Italian population, based on a multicenter, randomized, double-blind, placebo-controlled trial.

Both PCF and naproxen sodium (550 mg) showed significant efficacy compared to placebo, but there was no significant difference in effectiveness between PCF and naproxen, indicating that PCF is a viable alternative for acute TTH treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and efficacy of a combination of paracetamol and caffeine in the treatment of tension-type headache: a randomised, double-blind, double-dummy, cross-over study versus placebo and naproxen sodium. Pini, LA., Del Bene, E., Zanchin, G., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5714807/

Effects of energy drinks on the cardiovascular system - PMC This result shows that participants who consumed more cups of coffee generally were significantly less likely to develop cardiac arrhythmias. This shows the ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0273230017302210

Caffeine and cardiovascular health Typical moderate caffeine intake is not associated with increased risks of total cardiovascular disease; arrhythmia; heart failure; blood pressure changes.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11648991/

Caffeine and Arrhythmias: A Critical Analysis of ... Chronic coffee drinking has also been linked to a lower risk of cardiovascular disease (CVD), which includes heart failure, stroke, and coronary heart disease ( ...

4. nature.com nature.com/articles/s41598-021-03158-2

Caffeine increases performance and leads to a ... Our study provided evidence that acute caffeine intake (6 mg∙kg −1 ) increased performance (time-trial) and demonstrated a relevant cardioprotective effect.

5. ahajournals.org ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.119.006799

Association Between Coffee Intake and Incident ... Higher coffee intake was found to be associated with reduced risk of HF in all three studies. Further study is warranted to better define the role.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK202224/

Caffeine Effects on the Cardiovascular System - NCBI - NIH Not surprisingly, in El-Sohemy's opinion, some have shown an increased risk of cardiovascular disease with caffeine exposure, others have shown no effect, and ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36995515/

Effect of Caffeine Consumption on Cardiovascular Disease The literature review revealed controversial clinical effects of caffeine on blood pressure, cardiac arrhythmias, acute coronary syndrome, stable angina, and ...

8. acc.org acc.org/About-ACC/Press-Releases/2024/08/15/14/46/New-Study-Finds-Chronic-High-Caffeine-Consumption-May-Heighten-Risk-for-Cardiovascular-Disease

New Study Finds Chronic High Caffeine Consumption May ... Drinking over 400 mg of caffeine per day on most days of the week could increase the susceptibility of otherwise healthy individuals to cardiovascular disease.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0939475325002698

Cardiovascular health and coffee: Insights from a recent ... provides compelling evidence that moderate coffee intake (1–3 cups per day) is associated with reduced all-cause and cardiovascular mortality, particularly ...

10. ahajournals.org ahajournals.org/doi/10.1161/JAHA.115.003089

Caffeine Consumption and Cardiovascular Risks The authors concluded that coffee consumption was associated with both coronary heart disease and stroke; the lowest CVD risk occurred at 3–5 cups per day.