Diet ModificationPhTINCT05113498
The Influence of the Microbiome on the Pharmacokinetics of Flavan-3-ols
A study testing (-)-Epicatechin in people with Diet Modification, run by University Ghent at 1 site in Belgium.
Trial summary
Cocoa beans are of major interest due to their various beneficial health effects, indicated to be caused by its cocoa flavan-3-ols. (-)-Epicatechin is the most abundant flavan-3-ol in these cocoa beans. Read more about this study
- Who is it for?
- Ages 18 to 30 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Diet Modification
- What is being tested?
- (-)-Epicatechin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Nov 2021to 26 Apr 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy
- Stable diet
- Stable exercise regimen
Who cannot join
- The use of antibiotics, pre- and probiotics in the last six months
- The use of chronic medication
- The use of any medication in the last 2 weeks
- Diarrhea in last 2 weeks
- Recent blood donations
- Vegan or vegetarian diets
- Smoking
- Chronic pathology or gastrointestinal disorders
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Influence of the Microbiome on the Pharmacokinetics of Flavan-3-ols After Acute Consumption in Healthy Young Male Participants
Cocoa beans are of major interest due to their various beneficial health effects, indicated to be caused by its cocoa flavan-3-ols. (-)-Epicatechin is the most abundant flavan-3-ol in these cocoa beans. Its metabolization in the colon results in bioactive valerolactone and valeric acid metabolites and derivatives after phase II metabolism. Interindividual differences in health effects following (-)-epicatechin consumption are observed, which are suggested to be caused by large interindividual differences in bioavailable metabolite concentrations. As the colonic microbiota is responsible for the metabolization of ~70% of total (-)-epicatechin intake, and ~42% of total (-)-epicatechin intake leads to valerolactone and valeric acid metabolites, it is hypothesized that the large interindividual variation in microbial gut composition is responsible for the heterogeneity in metabolite concentration and in its subsequent health effects. Furthermore, individuals can be stratified into two pharmacotypes, slow and fast microbial metabolizers, which can produce metabolites at different rates.
The aim of this single-arm study is to investigate if the microbial composition in the gut determines the rate and extent of metabolization, following an acute consumption of about 160mg of pure (-)-epicatechin. The pharmacokinetics of the (-)-epicatechin metabolites will be followed in plasma over 48h with a focus on the first fifteen hours and potentially in urine over 24h. Valerolactone and valeric acid metabolite profiles in plasma and urine will be obtained by Q-TOF-LC-MS. The microbial fingerprint of each individual will be obtained via DNA extraction, flow cytometry and 16s rRNA sequencing of fecal samples.
Read the detailed description
The aim of this study is to investigate if the microbial composition in the gut can determine the rate and extent of valerolactone and valeric acid production following an acute consumption of 160mg of pure (-)-epicatechin. The gut microbial composition of each participant will be linked with its metabolite plasma profile to investigate if the large interindividual variation in metabolite formation can be explained by the variation in microbial composition in the colon. This knowledge might contribute to a better understanding of the correlation between epicatechin intake and its observed beneficial, but at the same time very variable health effects.
This single-arm trial lasts a total of five days, with one day (day 3) on site at the laboratory (UZ Ghent, Department of Rehabilitation Sciences). Two days prior to the test day, subjects will be instructed to follow a low-flavan-3-ol diet for the next five days, until 48h after the supplement intake, to establish a low dietary background of flavan-3-ols. A list of restrictions on foods and beverages rich in flavan-3-ols, such as chocolate, tea, red wine and some fruit and vegetables, will be provided. Moreover, a standardized flavan-3-ol-free meal and snack will be provided to consume the evening prior to the test day, together with at least 0.5L of water. One day prior to the test day, each participant will collect a stool sample for the determination of their microbial fingerprint. Stool collection material will be provided to the subjects on beforehand. In addition, no strenuous exercise can be performed on this day.
On the test day, participants arrive at the laboratory around 8am after an overnight fast of minimum 8h and maximum 14h. This day lasts approximately 15h, until 11pm. First, a questionnaire will be completed to evaluate compliance with the instructed diet and to check the general well-being of the participants. Second, a medical doctor will insert a catheter in the median cubital vein in the forearm, after which a first blood sample will be drawn. Third, participants will be asked to empty the bladder, have breakfast and take the epicatechin supplement within ten minutes after breakfast. Standardized flavan-3-ol-free breakfast, lunch, dinner and three snacks will be offered at scheduled time points throughout the day. Water is ad libitum with a minimum of 1.5L. Lastly, a food frequency questionnaire will be completed.
Each hour after supplement intake, venous blood will be drawn in vacutainers until fifteen samples of 4mL are collected (0h-14h). On time points 0, 2, 6, 8 and 12h, additional blood samples will be drawn in serum vacutainers. Urine will be pooled in three timeframes (0-6h, 6-12h and 12-24h). When all blood samples are collected, the catheter will be removed and a questionnaire will be completed to evaluate the test day and well-being of the participants. On each of the two following mornings (24h and 48h), one additional blood sample will be taken after an overnight fast. The pooled urine (12-24h) will be collected 24h after supplement intake. Some participants will also conduct this trial without the (-)-epicatechin supplement to verify the effectiveness of the flavan-3-ol-free diet .
Valerolactone and valeric acid metabolite profiles will be obtained by Quadrupole Time of Flight Liquid chromatography-mass spectrometry (Q-TOF-LC-MS). The microbial fingerprint of each individual will be obtained via DNA extraction, flow cytometry and 16s rRNA sequencing of fecal samples.
- Conditions
- Diet Modification
- Being tested
- (-)-Epicatechin
- Keywords
- Valerolactones, (-)-Epicatechin, Microbiota, Pharmacokinetics, Interindividual differences, Q-TOF-LC-MS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
(-)-EpicatechinDietary supplement
Administration of a capsule with 150 mg of pure (-)-epicatechin after 48h low-flavanol diet.
| Study group | Role | What they receive |
|---|---|---|
| (-)-Epicatechin | Experimental | (-)-Epicatechin supplementation Receives: Dietary Supplement: (-)-Epicatechin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessing the formation of phase II valerolactone and valeric acid metabolites over time in blood.
Assessing the concentration of colonic valerolactone and valeric acid metabolites over time in blood by Q-TOF-LC-MS, after the consumption of 160g pure (-)-epicatechin, to identify poor and extensive metabolizers.
Measured: 48 hours
Identification of the bacteria on genus level in fecal samples of participants.
All bacteria in the fecal samples of participants will be identified by 16S rRNA gene-based analysis on genus level.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2021
- Study start1 Nov 2021
- Primary completion26 Apr 2022
- Study completion26 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diet ModificationStudies of the same condition, open and under way.
- More trials run by University GhentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single-dose study where all participants consume one epicatechin supplement.
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Ghent
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ernst Rietzschel, PhD, Principal investigator, University Hospital, Ghent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05113498
- Sponsor's protocol ID
- BC-09585
- Acronym
- PhTI
- Status last verified
- Apr 2022
- First submitted
- 15 Oct 2021
- Last updated
- 27 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: After publication (or during the review process) of the scientific paper individual data will be made available upon request to the corresponding author. Data that allows for identification of the participants will never be provided.
Publications
Mena P, Bresciani L, Brindani N, Ludwig IA, Pereira-Caro G, Angelino D, Llorach R, Calani L, Brighenti F, Clifford MN, Gill CIR, Crozier A, Curti C, Del Rio D. Phenyl-gamma-valerolactones and phenylvaleric acids, the main colonic metabolites of flavan-3-ols: synthesis, analysis, bioavailability, and bioactivity. Nat Prod Rep. 2019 May 22;36(5):714-752. doi: 10.1039/c8np00062j.
PubMed 30468210
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of the Microbiome on the Pharmacokinetics of Flavan-3-ols After Acute Consumption in Healthy Young Male Participants
- ClinicalTrials.gov ID
- NCT05113498
- Acronym / sponsor ID
- PhTI / BC-09585
- Conditions
- Diet Modification
- Keywords
- Valerolactones, (-)-Epicatechin, Microbiota, Pharmacokinetics, Interindividual differences, Q-TOF-LC-MS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University GhentUniversity, hospital or other
- Study start
- 1 Nov 2021 (actual)
- Primary completion
- 26 Apr 2022 (actual)
- Study completion
- 26 Apr 2022 (actual)
- First posted
- 9 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cocoa beans are of major interest due to their various beneficial health effects, indicated to be caused by its cocoa flavan-3-ols. (-)-Epicatechin is the most abundant flavan-3-ol in these cocoa beans. Its metabolization in the colon results in bioactive valerolactone and valeric acid metabolites and derivatives after phase II metabolism. Interindividual differences in health effects following (-)-epicatechin consumption are observed, which are suggested to be caused by large interindividual differences in bioavailable metabolite concentrations. As the colonic microbiota is responsible for the metabolization of ~70% of total (-)-epicatechin intake, and ~42% of total (-)-epicatechin intake leads to valerolactone and valeric acid metabolites, it is hypothesized that the large interindividual variation in microbial gut composition is responsible for the heterogeneity in metabolite concentration and in its subsequent health effects. Furthermore, individuals can be stratified into two pharmacotypes, slow and fast microbial metabolizers, which can produce metabolites at different rates.
The aim of this single-arm study is to investigate if the microbial composition in the gut determines the rate and extent of metabolization, following an acute consumption of about 160mg of pure (-)-epicatechin. The pharmacokinetics of the (-)-epicatechin metabolites will be followed in plasma over 48h with a focus on the first fifteen hours and potentially in urine over 24h. Valerolactone and valeric acid metabolite profiles in plasma and urine will be obtained by Q-TOF-LC-MS. The microbial fingerprint of each individual will be obtained via DNA extraction, flow cytometry and 16s rRNA sequencing of fecal samples.
Detailed description
The aim of this study is to investigate if the microbial composition in the gut can determine the rate and extent of valerolactone and valeric acid production following an acute consumption of 160mg of pure (-)-epicatechin. The gut microbial composition of each participant will be linked with its metabolite plasma profile to investigate if the large interindividual variation in metabolite formation can be explained by the variation in microbial composition in the colon. This knowledge might contribute to a better understanding of the correlation between epicatechin intake and its observed beneficial, but at the same time very variable health effects.
This single-arm trial lasts a total of five days, with one day (day 3) on site at the laboratory (UZ Ghent, Department of Rehabilitation Sciences). Two days prior to the test day, subjects will be instructed to follow a low-flavan-3-ol diet for the next five days, until 48h after the supplement intake, to establish a low dietary background of flavan-3-ols. A list of restrictions on foods and beverages rich in flavan-3-ols, such as chocolate, tea, red wine and some fruit and vegetables, will be provided. Moreover, a standardized flavan-3-ol-free meal and snack will be provided to consume the evening prior to the test day, together with at least 0.5L of water. One day prior to the test day, each participant will collect a stool sample for the determination of their microbial fingerprint. Stool collection material will be provided to the subjects on beforehand. In addition, no strenuous exercise can be performed on this day.
On the test day, participants arrive at the laboratory around 8am after an overnight fast of minimum 8h and maximum 14h. This day lasts approximately 15h, until 11pm. First, a questionnaire will be completed to evaluate compliance with the instructed diet and to check the general well-being of the participants. Second, a medical doctor will insert a catheter in the median cubital vein in the forearm, after which a first blood sample will be drawn. Third, participants will be asked to empty the bladder, have breakfast and take the epicatechin supplement within ten minutes after breakfast. Standardized flavan-3-ol-free breakfast, lunch, dinner and three snacks will be offered at scheduled time points throughout the day. Water is ad libitum with a minimum of 1.5L. Lastly, a food frequency questionnaire will be completed.
Each hour after supplement intake, venous blood will be drawn in vacutainers until fifteen samples of 4mL are collected (0h-14h). On time points 0, 2, 6, 8 and 12h, additional blood samples will be drawn in serum vacutainers. Urine will be pooled in three timeframes (0-6h, 6-12h and 12-24h). When all blood samples are collected, the catheter will be removed and a questionnaire will be completed to evaluate the test day and well-being of the participants. On each of the two following mornings (24h and 48h), one additional blood sample will be taken after an overnight fast. The pooled urine (12-24h) will be collected 24h after supplement intake. Some participants will also conduct this trial without the (-)-epicatechin supplement to verify the effectiveness of the flavan-3-ol-free diet .
Valerolactone and valeric acid metabolite profiles will be obtained by Quadrupole Time of Flight Liquid chromatography-mass spectrometry (Q-TOF-LC-MS). The microbial fingerprint of each individual will be obtained via DNA extraction, flow cytometry and 16s rRNA sequencing of fecal samples.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single-dose study where all participants consume one epicatechin supplement.
| Arm | Type | Receives |
|---|---|---|
| (-)-Epicatechin | Experimental | Dietary Supplement: (-)-Epicatechin(-)-Epicatechin supplementation |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy
- Stable diet
- Stable exercise regimen
Key exclusion criteria (8 listed)
- The use of antibiotics, pre- and probiotics in the last six months
- The use of chronic medication
- The use of any medication in the last 2 weeks
- Diarrhea in last 2 weeks
- Recent blood donations
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| (-)-EpicatechinAdministration of a capsule with 150 mg of pure (-)-epicatechin after 48h low-flavanol diet. | Dietary supplement | (-)-Epicatechin |
Primary outcome
Assessing the formation of phase II valerolactone and valeric acid metabolites over time in blood.
Time frame: 48 hours
Assessing the concentration of colonic valerolactone and valeric acid metabolites over time in blood by Q-TOF-LC-MS, after the consumption of 160g pure (-)-epicatechin, to identify poor and extensive metabolizers.
Identification of the bacteria on genus level in fecal samples of participants.
Time frame: Baseline
All bacteria in the fecal samples of participants will be identified by 16S rRNA gene-based analysis on genus level.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2022.
- Background: PubMed 30468210Mena P, Bresciani L, Brindani N, Ludwig IA, Pereira-Caro G, Angelino D, Llorach R, Calani L, Brighenti F, Clifford MN, Gill CIR, Crozier A, Curti C, Del Rio D. Phenyl-gamma-valerolactones and phenylvaleric acids, the main colonic metabolites of flavan-3-ols: synthesis, analysis, bioavailability, and bioactivity. Nat Prod Rep. 2019 May 22;36(5):714-752. doi: 10.1039/c8np00062j.
- Individual participant dataSharing planned: No. After publication (or during the review process) of the scientific paper individual data will be made available upon request to the corresponding author. Data that allows for identification of the participants will never be provided.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ernst Rietzschel, PhD principal investigator
University Hospital, Ghent
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing (-)-Epicatechin in people with Diet Modification, run by University Ghent at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessing the formation of phase II valerolactone and valeric acid metabolites over time in blood. (time frame: 48 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05113498, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2022.