Effect of Caffeine Consumption on Protein Biomarkers and Cardiovascular Disease

NCT06359197 | Not Yet Recruiting Early Phase 1 FDA Drug FDA Device

• 1 other identifier: 2024-17022-GRA
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Healthy

Keywords

Caffeine; Protein Biomarkers; Proteomics; Feasibility; TASSO; Dried Blood Spot (DBS); Capillary blood

Outcome Measures

Primary Outcomes (3)

• Participant rate

  To evaluate participant rate, the investigators will determine (1) how many participants enter the study at a time, (2) how long it takes to recruit enough participants into the study, and (3) what are the refusal rates for participation. Their goal is to have a participant rate of 75%, meaning that they are able to recruit 75% of the people that are approached.

  From enrollment to the end of intervention at 6 hours post caffeine or placebo consumption

• Participant Adherence

  To evaluate participant adherence, the investigators will determine the retention and follow-up rates as the participants move through the study. Their goal is to have an adherence rate of 95% as this will help to avoid attrition bias, which will ensure that there will be no significant differences between the analyzed cohort vs. participants who were lost to follow-up or withdrew from the study.

  From enrollment to the end of intervention at 6 hours post caffeine or placebo consumption

• Participant satisfaction

  User experience with the capillary blood collection devices will be evaluated using a satisfaction survey. Participants will rate their experience using a 5-point Likert scale ranging from extremely difficult (1 point) to extremely easy (5 points) for four questions related to ease-of-use, and from not usable (1 point) to no pain (5 points) for one question related to comfort of use. The investigators will consider a score of ≥20 to indicate acceptability and suitability of the device. They will consider achieving a satisfaction score of ≥20 from \>80% of participants to be feasible.

  From enrollment to the end of intervention at 6 hours post caffeine or placebo consumption

Secondary Outcomes (3)

• Significant changes in biomarkers observed after the ingestion of caffeine

  From enrollment to the end of intervention at 6 hours post caffeine or placebo consumption

• Determine the correlation between capillary sampling and intravenous sampling

  From enrollment to the end of intervention at 6 hours post caffeine or placebo consumption in phase 1 cohort

• Determine the stability of capillary samples

  From enrollment to the end of intervention at 6 hours post caffeine or placebo consumption

Study Arms (4)

Caffeine - Phase 1

EXPERIMENTAL

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.

Drug: Caffeine Pill; Device: TASSO+ Device; Device: Finger prick and collection on Whatman Protein 903 Saver Cards; Device: Intravenous Sampling

Control - Phase 1

PLACEBO COMPARATOR

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.

Drug: Placebo; Device: TASSO+ Device; Device: Finger prick and collection on Whatman Protein 903 Saver Cards; Device: Intravenous Sampling

Caffeine - Phase 2

EXPERIMENTAL

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.

Drug: Caffeine Pill; Device: TASSO+ Device

Control - Phase 2

PLACEBO COMPARATOR

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.

Drug: Placebo; Device: TASSO+ Device

Interventions

Caffeine Pill DRUG

Participants would take two Wake-Ups 200mg Caffeine tablets to meet the target dose of 400mg of caffeine. These are a registered natural health product with Health Canada (NPN 80003474). They are developed by Adrem Brands, which was established in 1951. Quality control testing is performed at a third-party independent lab, Nucro-Technics, which is audited by Health Canada and the US FDA. This ensures that the caffeine tablets comply with Health Canada standards. The tablets contain caffeine anhydrous-a processed, dehydrated form of caffeine-which allows for a standard dose per tablet. The tablets are sugar-free, which reduces the confounding effect of sugar on our results; thus, the investigators can be more confident that the obtained results are reflective of the association between caffeine and the CVD-related protein biomarkers.

Caffeine - Phase 1; Caffeine - Phase 2

Placebo DRUG

Participants would take two placebo pills to match the dosage of the intervention group. The investigators will use empty vegetable capsules from Health Bloom as the placebo for the control group. These capsules contain no contaminants or additives and are free from the common allergens. They are sugar-free-unlike most placebo pills, which reduces the confounding effect of sugar on our results. They are developed by Health Bloom, which is a Canadian company established in 2015. These capsules undergo testing at various stages of production to ensure purity and quality control. Each ingredient is tested prior to formulation, and the final capsules are subjected to thorough testing post-development. The capsules are white, and similar in appearance to the caffeine pill given to participants in the intervention group.

Control - Phase 1; Control - Phase 2

TASSO+ Device DEVICE

TASSO+ is a blood lancet device that uses negative pressure to draw capillary blood from the upper arm into a standard SST tube of volume 500μL. The small volume of blood collected makes this device less invasive than traditional collection methods. It is also safer and easier to use since it offers automated sample collection. TASSO manufactures a number of special devices for capillary blood sampling that have been validated as safe for consumer use, and the Tasso+ device is licensed with Health Canada for research use.

Caffeine - Phase 1; Caffeine - Phase 2; Control - Phase 1; Control - Phase 2

Finger prick and collection on Whatman Protein 903 Saver Cards DEVICE

The Whatman Protein 903 Saver Card is a specialized filter paper designed for the collection, storage, and elution of biological samples, including blood. It contains five half-inch circles that hold 75 to 80 µL of blood, making it an efficient and reliable method of obtaining dried blood spot (DBS) samples. The participant's finger will be pricked using a sterile, disposable lancet, and drops of blood will be collected on the Whatman 903 Protein Saver Card to fill nine ½ inch discs via capillary action. The blood spots will be allowed to dry at ambient temperature (21°C) for two hours. Whatman Protein 903 Saver Cards undergo strict quality control and GMP manufacturing standards, which ensures high quality and reproducibility.

Caffeine - Phase 1; Control - Phase 1

Intravenous Sampling DEVICE

Blood will be collected from the medial cubital vein according to the standard venous blood sampling protocol into an EDTA tube with a volume up to 4mL.

Caffeine - Phase 1; Control - Phase 1

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Participants must be over the age of 18 to participate in the study. This is based on 400mg of caffeine being deemed safe for healthy adults.

You may not qualify if:

• Participants are not to be pregnant or trying to get pregnant or lactating as the recommended caffeine consumption for these individuals is less than what would be administered 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.
• Individuals with the following conditions will be excluded from the study: Hypertension or a history of hypertension Glaucoma Thyroid disease Heart disease Seizure disorder The investigators will screen the participant's medical conditions and not include anyone whose condition may interfere.
• Individuals who experience anxiety or have been diagnosed with other mental illnesses will want to consider their participation in this study. Those who experience anxiety may experience more anxiety-related symptoms with the consumption of caffeine. The investigators will screen participant's for anxiety-related disorders.
• Individuals who have recently undergone major surgery. Major surgery is any intervention that has resulted in the penetration and opening of a body cavity (i.e., chest or abdominal). Recent is within the last month.
• Individuals who are taking medication which may have adverse interactions with caffeine will be excluded from the study. The investigators will screen the participant's medications and not include anyone whose medications may interfere.

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead

Study Sites (3)

David Braley Research Institute

Hamilton, Ontario, L8L 2X2, Canada

Location

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

McMaster University, Department of Pathology and Molecular Medicine

Hamilton, Ontario, L8S 4L8, Canada

Location

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• Numao S, Uchida R, Kurosaki T, Nakagaichi M. Differences in circulating fatty acid-binding protein 4 concentration in the venous and capillary blood immediately after acute exercise. J Physiol Anthropol. 2021 Feb 10;40(1):5. doi: 10.1186/s40101-021-00255-z.

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• Wik L, Nordberg N, Broberg J, Bjorkesten J, Assarsson E, Henriksson S, Grundberg I, Pettersson E, Westerberg C, Liljeroth E, Falck A, Lundberg M. Proximity Extension Assay in Combination with Next-Generation Sequencing for High-throughput Proteome-wide Analysis. Mol Cell Proteomics. 2021;20:100168. doi: 10.1016/j.mcpro.2021.100168. Epub 2021 Oct 27.

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• Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010 Nov;5(6):463-6. doi: 10.1097/COH.0b013e32833ed177.

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• O'Keefe JH, DiNicolantonio JJ, Lavie CJ. Coffee for Cardioprotection and Longevity. Prog Cardiovasc Dis. 2018 May-Jun;61(1):38-42. doi: 10.1016/j.pcad.2018.02.002. Epub 2018 Feb 21.

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• Brown J, Kreiger N, Darlington GA, Sloan M. Misclassification of exposure: coffee as a surrogate for caffeine intake. Am J Epidemiol. 2001 Apr 15;153(8):815-20. doi: 10.1093/aje/153.8.815.

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• Lewis M, Bromley K, Sutton CJ, McCray G, Myers HL, Lancaster GA. Determining sample size for progression criteria for pragmatic pilot RCTs: the hypothesis test strikes back! Pilot Feasibility Stud. 2021 Feb 3;7(1):40. doi: 10.1186/s40814-021-00770-x.

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• Temple JL, Bernard C, Lipshultz SE, Czachor JD, Westphal JA, Mestre MA. The Safety of Ingested Caffeine: A Comprehensive Review. Front Psychiatry. 2017 May 26;8:80. doi: 10.3389/fpsyt.2017.00080. eCollection 2017.

  PMID: 28603504 BACKGROUND

• Nawrot P, Jordan S, Eastwood J, Rotstein J, Hugenholtz A, Feeley M. Effects of caffeine on human health. Food Addit Contam. 2003 Jan;20(1):1-30. doi: 10.1080/0265203021000007840.

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• Eshghi A, Pistawka AJ, Liu J, Chen M, Sinclair NJT, Hardie DB, Elliott M, Chen L, Newman R, Mohammed Y, Borchers CH. Concentration Determination of >200 Proteins in Dried Blood Spots for Biomarker Discovery and Validation. Mol Cell Proteomics. 2020 Mar;19(3):540-553. doi: 10.1074/mcp.TIR119.001820. Epub 2020 Jan 2.

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• Bjorkesten J, Enroth S, Shen Q, Wik L, Hougaard DM, Cohen AS, Sorensen L, Giedraitis V, Ingelsson M, Larsson A, Kamali-Moghaddam M, Landegren U. Stability of Proteins in Dried Blood Spot Biobanks. Mol Cell Proteomics. 2017 Jul;16(7):1286-1296. doi: 10.1074/mcp.RA117.000015. Epub 2017 May 13.

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• Fontaine E, Saez C. Capillary blood stability and analytical accuracy of 12 analytes stored in Microtainers(R). Pract Lab Med. 2023 Jul 5;36:e00325. doi: 10.1016/j.plabm.2023.e00325. eCollection 2023 Aug.

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Related Links

• Whatman 903 Protein Saver Cards
• OLINK Target 96 CVD III panel
• TASSO+ Device
• Caffeine pills used in study
• Placebo pills used in study

MeSH Terms

Interventions

Caffeine

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Guillaume Pare, MD

  Population Health Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Megan Robertson

CONTACT

905-527-4322; caffeine@crlb-gmel.ca

Luca Malatesta

CONTACT

905-527-4322; caffeine@crlb-gmel.ca

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: An external party will prepare an equal number of kits (n=18) containing all the required materials for the participants, both in the placebo and caffeine group. They will assign a unique random number to each of the packages; each number will correlate to either the placebo or caffeine group. When a participant agrees to the study, they will be given a unique participant ID number ranging from 0-36. Then, the external party will use a random number generator to pick the kit given to that participant. They will record the number associated with that kit, and link the kit number to the participant ID for tracking purposes. At the end of the study, the investigators will determine which participants received caffeine vs placebo based on the assigned random numbers.

Study Record Dates

• First Submitted: April 2, 2024
• First Posted: April 11, 2024
• Study Start: April 8, 2024
• Primary Completion: August 10, 2024
• Study Completion: June 1, 2025
• Last Updated: April 11, 2024

Record last verified: 2024-04

Locations

CA (3)