Caffeine for Cardiovascular Disease

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

36 Participants Needed

Trial Summary

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.

What evidence supports the effectiveness of caffeine as a drug for cardiovascular disease?

Research shows that caffeine, when combined with other pain relievers like acetaminophen or ibuprofen, is effective in treating tension-type headaches, suggesting its potential as an analgesic (pain reliever). However, there is no direct evidence from the provided studies supporting its effectiveness specifically for cardiovascular disease. ^{1 2 3 4 5}

Is caffeine safe for use in humans?

Research shows that caffeine, when combined with other medications like paracetamol, is generally safe and well-tolerated in humans, with no significant difference in safety compared to other treatments like naproxen sodium or placebo. ^{1 2 5 6 7}

How does caffeine differ from other drugs for cardiovascular disease?

Caffeine is unique because it is a common stimulant found in many everyday products like coffee and tea, and it works by blocking adenosine receptors, which can increase heart rate and blood pressure. Unlike other cardiovascular drugs that may focus on reducing cholesterol or improving blood flow, caffeine's primary action is stimulating the central nervous system. ^{8 9 10 11 12}

What is the purpose of this trial?

Caffeine is one of the most widely consumed substances worldwide. This study looks to test and measure the changes in different biomarkers in the blood before and after having caffeine using capillary and venous blood sampling methods. A biomarker is a measurable indicator of biological processes. The primary goal of this clinical trial is to evaluate participant rate and adherence. It will also learn about how caffeine affects different biomarkers that may be related to cardiovascular disease. Finally, it will assess the accuracy of the capillary blood samples compared to the venous blood samples. The main questions it aims to answer are: * What is the feasibility of recruiting and retaining participants? * Are the study procedures appropriate to be translated to a larger future study? Researchers will compare caffeine to a placebo (a look-alike substance that contains no drug) to see if Participants will: * Be randomly assigned to the control group or the caffeine group. Individuals in the control group will be taking a placebo pill with no effect and those in the caffeine group will be taking 400mg of caffeine in pill form. * Be asked to undergo a fast of at least 8 hours overnight before taking two placebo pills or the 400 mg of caffeine via two caffeine pills. They will be required to stay fasted for 6 hours after taking the pill as well. The total time fasted will be at least 14 hours. * Have blood collected using three different methods before taking the two pills, 3 hours after taking the pills and 6 hours after taking the pills. The 3 methods include intravenous (IV) blood sampling, finger prick and collection on Whatman 903 Protein Saver Card and collection using the TASSO+ device. The TASSO+ blood collection device is a small capillary blood collection device that is designed to be easy to use and able to be used outside of a hospital/lab setting. Whatman 903 Protein Saver Cards are special filter paper with five circles for samples, that are designed for the collection and storage of blood.

Research Team

Guillaume Pare, MD

Principal Investigator

Population Health Research Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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 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 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]

References

1. England 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. [2018]

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

The use of ibuprofen plus caffeine to treat tension-type headache. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

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

4. Canada 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. [2015]

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

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

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

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

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

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

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

[Efficacy of emoxipine and mexidol in patients with chronic disorders of the digestive system and atherosclerosis of the abdominal aorta]. [2016]

9. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of breviscapine injection in treatment of unstable angina pectoris: systematic review and Meta-analysis]. [2019]

10. United States 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. [2022]

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

Experimental substantiation for the use of mexidol and 3-hydroxypyridine fumarate in chronic myocardial injury. [2019]

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

[Trimetazidine addition to antianginal therapy: effects on efficacy and quality of life in patients with stable angina treated outpatiently]. [2013]