Clinical trial NCT06359197: Effect of Caffeine Consumption on Protein Biomarkers and Cardiovascular Disease
Official title: Feasibility Study for Investigating the Effect of Caffeine Consumption on Protein Biomarkers Related to Cardiovascular Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Healthy
Keywords: Caffeine
Protein Biomarkers
Proteomics
Feasibility
TASSO
Dried Blood Spot (DBS)
Capillary blood
Lead sponsor: Hamilton Health Sciences Corporation
Sponsor class: OTHER
First posted: 2024-04-11
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: OTHER

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.

Detailed description: Proteomic biomarkers related to disease risk factors may shed light on the pathogenesis of different diseases. There is a knowledge gap in the effects of lifestyle interventions on the proteome, mainly because collection of blood samples by venipuncture for proteomics analysis is tedious and expensive. Discovering an at-home capillary blood collection method with samples that contain protein profiles that mirror or can be correlated to those of venous samples has the potential to greatly improve access to research studies. Cardiovascular diseases (CVD) are the most common cause of death worldwide. Caffeine is a commonly consumed substance. Many studies have shown a relationship between caffeine and reduced risk of CVD; however, the mechanisms remain mostly unknown.

The investigators are conducting a two-part feasibility study examining the effect of caffeine consumption on the relative levels of 92 cardiovascular-related protein biomarkers in samples obtained using different blood collection technologies to compare protein profiles between capillary and venous blood samples and further clarify the protective mechanisms of caffeine in mitigating CVD risk. By integrating both of these components into a single trial, the investigators aim to reduce the burden placed on participants, making the study easier and more accessible.

For the preliminary testing of the at-home blood collection methods compared with intravenous sampling, a group of 10 individuals (evenly split between male and female) will be recruited. In this phase, participants will be subject to blood collection by intravenous sampling, as well as the TASSO+ device and finger prick and collection on Whatman Protein 903 Saver Cards. After the first portion of the study is complete, data from the 10 patients will be analyzed to determine the most accurate and reliable capillary blood collection device. This sampling device will show a reasonable correlation to venipuncture, with a threshold of correlation above 70%.

For the larger at-home testing of the selected blood collection method, a group of 26 individuals will participate, again, with an even split between males and females. Participants in this second cohort will no longer have to come on premise for intravenous sampling. They can complete the entire study remotely, further reducing logistical challenges. In this phase, blood will only be collected using the capillary blood collection device that best correlates with venipuncture as validated in the first part of the study.

After the second portion of the study is complete, data from the first 10 participants will be integrated and compared with data from the second 26 participants to evaluate the effect of caffeine vs placebo on biomarkers, as well as identify any significant differences between the two cohorts.

In both phases, participants will undergo a fast of at least 8 hours prior to the administration of the caffeine or placebo. Following this fast, blood will be collected (either at home or in the lab) prior to the ingestion of the caffeine pill or placebo. Blood will also be collected at 3 and 6 hours after the ingestion of the caffeine pill or placebo. Blood samples will either be collected in the lab or collected at-home then mailed back to the lab, and stored in a -80°C freezer until proteomic analysis may be conducted to investigate the changes in biomarkers.

With this being a feasibility study, the investigators are hoping to see some results from this sample size, then translate their findings to a larger study with more participants conducted over a longer period of time in the future.

Eligibility criteria: Inclusion Criteria:

- 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Participant rate
timeFrame: From enrollment to the end of intervention at 6 hours post caffeine or placebo consumption
measure: Participant Adherence
timeFrame: From enrollment to the end of intervention at 6 hours post caffeine or placebo consumption
measure: Participant satisfaction
timeFrame: From enrollment to the end of intervention at 6 hours post caffeine or placebo consumption
Secondary outcomes:
measure: Significant changes in biomarkers observed after the ingestion of caffeine
timeFrame: From enrollment to the end of intervention at 6 hours post caffeine or placebo consumption
measure: Determine the correlation between capillary sampling and intravenous sampling
timeFrame: From enrollment to the end of intervention at 6 hours post caffeine or placebo consumption in phase 1 cohort
measure: Determine the stability of capillary samples
timeFrame: From enrollment to the end of intervention at 6 hours post caffeine or placebo consumption
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: David Braley Research Institute
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: McMaster University, Department of Pathology and Molecular Medicine
state: Ontario
Study officials:
affiliation: Population Health Research Institute
name: Guillaume Pare, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jett JD, Beck R, Tyutyunnyk D, Sanchez J, Lopez-Cruzan M, Ginsburg BC, McPherson SM, Javors MA, McDonell MG, Hill-Kapturczak N. Validation of the quantification of phosphatidylethanol 16:0/18:1 concentrations in TASSO-M20 devices. Alcohol Clin Exp Res (Hoboken). 2023 Apr;47(4):748-755. doi: 10.1111/acer.15024. Epub 2023 Feb 21.
citation: Shen X, Kellogg R, Panyard DJ, Bararpour N, Castillo KE, Lee-McMullen B, Delfarah A, Ubellacker J, Ahadi S, Rosenberg-Hasson Y, Ganz A, Contrepois K, Michael B, Simms I, Wang C, Hornburg D, Snyder MP. Multi-omics microsampling for the profiling of lifestyle-associated changes in health. Nat Biomed Eng. 2024 Jan;8(1):11-29. doi: 10.1038/s41551-022-00999-8. Epub 2023 Jan 19.
citation: 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.
citation: 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.
citation: Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010 Nov;5(6):463-6. doi: 10.1097/COH.0b013e32833ed177.
citation: 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.
citation: 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.
citation: 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.
citation: Lebeau PF, Byun JH, Platko K, Saliba P, Sguazzin M, MacDonald ME, Pare G, Steinberg GR, Janssen LJ, Igdoura SA, Tarnopolsky MA, Wayne Chen SR, Seidah NG, Magolan J, Austin RC. Caffeine blocks SREBP2-induced hepatic PCSK9 expression to enhance LDLR-mediated cholesterol clearance. Nat Commun. 2022 Feb 9;13(1):770. doi: 10.1038/s41467-022-28240-9.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Knitza J, Tascilar K, Vuillerme N, Eimer E, Matusewicz P, Corte G, Schuster L, Aubourg T, Bendzuck G, Korinth M, Elling-Audersch C, Kleyer A, Boeltz S, Hueber AJ, Kronke G, Schett G, Simon D. Accuracy and tolerability of self-sampling of capillary blood for analysis of inflammation and autoantibodies in rheumatoid arthritis patients-results from a randomized controlled trial. Arthritis Res Ther. 2022 May 25;24(1):125. doi: 10.1186/s13075-022-02809-7.
citation: Wickremsinhe E, Fantana A, Berthier E, Quist BA, Lopez de Castilla D, Fix C, Chan K, Shi J, Walker MG, Kherani JF, Knoderer H, Regev A, Harding JJ. Standard Venipuncture vs a Capillary Blood Collection Device for the Prospective Determination of Abnormal Liver Chemistry. J Appl Lab Med. 2023 May 4;8(3):535-550. doi: 10.1093/jalm/jfac127.
citation: Khiali S, Agabalazadeh A, Sahrai H, Bannazadeh Baghi H, Rahbari Banaeian G, Entezari-Maleki T. Effect of Caffeine Consumption on Cardiovascular Disease: An Updated Review. Pharmaceut Med. 2023 Mar;37(2):139-151. doi: 10.1007/s40290-023-00466-y. Epub 2023 Mar 30.