Clinical trial NCT06758531: Coffee Bioequivalence Trial
Official title: Coffee Bioequivalence Trial: Comparing the Pharmacokinetics of Bioactive Components and Physiological Effects of Consuming Encapsulated Instant Coffee Versus Traditional Instant Coffee Brewed in Water
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Liver Functions
Bioequivalence
Cardiovascular Risk
Cardiometabolic Risk Markers
Keywords: Coffee
Bioequivalence
Caffeine
Liver function
Polyphenols
Blood pressure
Cardiovascular disease
Chlorogenic acids
Lead sponsor: University of Reading
Sponsor class: OTHER
First posted: 2025-01-03
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The goal of this clinical trial is to test if coffee consumed as a tablet is biologically equivalent to that consumed traditionally as a drink. It will also learn about the impact of the short-term intake of coffee on markers of cardiovascular and liver health. The main questions it aims to answer are:

* Do coffee bioactive compounds produce the same levels in blood and urine regardless of how the coffee is consumed (tablet or drink)?
* How does coffee as a tablet or drink impact cardiovascular risk and liver health versus a non-coffee control?

Participants will:

* Visit the clinical unit for three phases; each phase is 1x 480 minute (eight hour) acute postprandial visit and 1 x one hour visit the following day. During each phase they will be randomly assigned to take a different intervention (coffee drink, coffee tablet, coffee-free control)
* Be cannulated during the 480 minute (8 hour) acute visits and have regular blood draws as well as basic clinical assessments
* Return on day two for a fasting blood sample and basic clinical assessment
* Collect their urine for 24 h
* Be asked to record their intake of foods and drinks for 3 days to assess their usual diet (dietary assessment).

Detailed description: Coffee has gained interest for its role in the prevention of non-communicable diseases such as heart and liver diseases. Population-based studies have reported that consuming 2-4 cups of coffee per day is associated with lower death rates and, notably reductions in the incidence of heart disease. However, these observational trials do not directly prove causality and carefully designed randomised controlled trials are needed.

This current trial will provide vital information to inform a large-scale randomised controlled trial assessing the effects of coffee consumption on risk markers for developing cardiometabolic disease (such as type 2 diabetes, heart and liver diseases) to test causality. In this follow-up trial to be conducted in 2025, non-coffee consumers will be recruited. To maximise recruitment, retention and adherence in the trial, we are considering providing instant coffee as tablets rather than as a drink. Hence, the current study will help to understand if coffee delivered in a tablet is biologically equivalent to consuming coffee as a drink.

A 3 armed, randomised, controlled crossover trial in healthy participants wil be performed. The primary outcome is the pharmacokinetic profile of coffee bioactives in coffee drink versus the coffee tablet. Secondary outcomes will be assessing the impact of the coffee both as a drink and tablet on cardiovascular and liver health markers (versus a coffee-free control).

Briefly, participants will attend three study phases. Each study phase includes a 480 minute (8-hour) acute postprandial visit and a shorter visit (\~one hour) the following morning. On the first day participants will arrive having fasted overnight and having followed dietary and lifestyle restrictions in the preceding days. They will have baseline anthropometric measures performed and a cannula will be inserted; two baseline blood samples will be collected (14 mL in total). Blood samples will be collected regularly from the cannula, and a clinic blood pressure measurement will be performed at regular intervals following the intervention (a different intervention will be given in a random order at each of the three phases). A breakfast meal and lunch will be provided to the participants during the visit and participants will leave with a standardised meal and snack to consume in the evening. They will return, fasted the following morning to provide a blood samples and have their blood pressure measured. Participants will be asked to collect their urine for 24h following the intervention; this will be returned that morning. There will be a 4-week period between each study phase.

Eligibility criteria: Inclusion Criteria:

* Healthy males and pre-menopausal females (must have regular menstrual cycles)
* Aged between 18 to 45 years
* Body mass index (BMI) between 18.5-30 kg/m2

Exclusion Criteria:

* Sensitivity to coffee and caffeine
* Food allergies relating to the test meals provided (such as gluten or lactose intolerance)
* Current smoking and vaping use.
* Medical history of chronic diseases (cancer, high blood pressure (hypertension), type 2 diabetes, heart attack and/or any other heart disease related diseases, gastrointestinal disorders, hyperlipidaemia, kidney or liver disease).
* Diagnosed with anaemia
* Prescribed any medication relating to the study outcome measures (such as blood pressure lowering, anti-inflammatories or blood thinners).
* Drinking more than the recommended intake for alcohol (\> 14 units/week)
* Taking any supplements (vitamins, minerals, probiotics).
* Any other unusual medical history or diet and lifestyle habits or practices that would preclude volunteers from participating in a dietary intervention and metabolic study (e.g. pacemaker)
* Planning on a weight-reducing regimen (lost \>3 kg in the last 6 months)
* Parallel participation in another intervention study
* Pregnancy, planning a pregnancy in the next 6 months or breastfeeding
* NHS blood donation in the last 3 months

Primary outcomes:
measure: Pharmacokinetic profile of key coffee biologically active compounds and their metabolites after consuming a coffee drink, a coffee tablet and control.
timeFrame: Blood taken prior to consuming the intervention (0 minutes) and then 30, 45, 60, 90, 120, 180, 240, 300, 360, 420, 480 and 1440 minutes post intervention.
measure: Pharmacokinetic profile of key coffee biologically active compounds and their metabolites after consuming a coffee drink, a coffee tablet and control.
timeFrame: Blood taken prior to consuming the intervention (0 minutes) and then 30, 45, 60, 90, 120, 180, 240, 300, 360, 420, 480 and 1440 minutes post intervention.
Secondary outcomes:
measure: Fasting concentrations of total cholesterol and high-density lipoprotein cholesterol.
timeFrame: Acute study days prior to the intervention (0 minutes).
measure: Fasting and postprandial lipids concentrations after consuming the coffee drink, coffee tablet and control interventions
timeFrame: Acute study days, blood taken prior to the intervention (0 minutes) and then 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 420 and 480 minutes.
measure: Fasting and postprandial glucose concentrations after consuming the coffee drink, coffee tablet and control interventions
timeFrame: Acute study days, blood taken prior to consuming the intervention (0 minutes) and then 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 420 and 480 minutes.
measure: Fasting and postprandial insulin concentrations after consuming the coffee drink, coffee tablet and control interventions
timeFrame: Acute study days, blood taken prior to consuming the intervention (0 minutes) and then 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 420 and 480 minutes.
measure: Fasting and postprandial liver enzyme concentrations after consuming the coffee drink, coffee tablet and control interventions
timeFrame: Acute study days, blood taken prior to consuming the intervention (0 minutes) and then 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 420 and 480 minutes.
measure: Fasting and postprandial gut hormone concentrations after consuming the coffee drink, coffee tablet and control interventions
timeFrame: Acute study days, blood taken prior to the intervention (0 minutes) and then 30, 60, 120, 180, 240, 300, 360 and 480 minutes.
measure: Fasting and postprandial plasma metabolomics after consuming the coffee drink, coffee tablet and control interventions
timeFrame: Acute study days, blood taken prior to the intervention (0 minutes) and then 30, 60, 120, 180, 240, 300, 360, 420 and 480 minutes.
measure: Fasting and postprandial plasma nitrate and nitrite concentrations after consuming the coffee drink, coffee tablet and control interventions
timeFrame: Acute study days, blood taken prior to the intervention (0 minutes) and then 15, 30, 45, 60, 120, 180, 240, 300, 360, 420 and 480 minutes.
measure: Urinary metabolomics
timeFrame: Urine will be collected prior to (0 minutes) and for 1440 minutes after each intervention.
measure: Urinary creatinine
timeFrame: Urine will be collected prior to (0 minutes) and for 1440 minutes after each intervention.
measure: Urinary osmolality and pH
timeFrame: Urine will be collected prior to (0 minutes) and for 1440 minutes after each intervention.
measure: Urinary sodium and potassium
timeFrame: Urine will be collected prior to (0 minutes) and for 1440 minutes after each intervention.
measure: Body weight
timeFrame: On each acute study visit prior to the collection of the first blood sample (0 minutes).
measure: Height
timeFrame: First acute study visit (0 minutes on visit 1)
measure: Blood pressure
timeFrame: -15, 30, 60, 120, 180, 240, 300, 360, 420, 480 minutes
measure: Body fat percentage
timeFrame: Each acute study visit (0 minutes)
measure: Body fat mass
timeFrame: On each acute study visit prior to the collection of the first blood sample (0 minutes).
measure: Body lean mass
timeFrame: On each acute study visit prior to the collection of the first blood sample (0 minutes).
measure: Body mass index
timeFrame: On each acute study visit (0 minutes)
measure: Waist and hip circumferences
timeFrame: On each acute study visit (0 minutes).
measure: Habitual dietary intake of the study participants
timeFrame: Two weeks prior to the first acute study visit (t- 2 weeks from visit 1).
measure: Fasting estimate of insulin resistance and insulin sensitivity
timeFrame: On each acute study visit (0 minutes).
measure: Fasting low-density lipoprotein-cholesterol concentration
timeFrame: On each acute study visit (0 minutes).
Other outcomes:
Locations:
city: Reading
country: United Kingdom
facility: Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading
state: Berkshire
Study officials:
affiliation: University of Reading
name: Abbe Davy, BSc
role: STUDY_DIRECTOR
References: