Trimethylamine N-oxide Effects of a Pomegranate Supplement Simultaneously With Carnitine (TESSA)
NCT Number: NCT06518343
Acronym: TESSA
Status: ENROLLING_BY_INVITATION
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Healthy
Interventions: DIETARY_SUPPLEMENT: L-carnitine + Pomegranate extract|DIETARY_SUPPLEMENT: L-carnitine + Microcrystalline cellulose
Sponsor: Quadram Institute Bioscience
Collaborators: Norfolk and Norwich University Hospitals NHS Foundation Trust|Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: TRIPLE (PARTICIPANT, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: BASIC_SCIENCE
Start Date: 2024-08-12
Completion Date: 2027-05-31
Locations: Quadram Institute, Norwich, Norfolk, NR4 7UQ, United Kingdom

Summary:
Trimethylamine N-oxide (TMAO) is produced in some individuals whose diets include meat, fish, and dairy.These foods are rich in L-carnitine. L-carnitine is metabolised by the liver and gut microorganisms (bacteria) into TMAO. In the TESSA study, investigators will explore whether pomegranate extract can lower the production of TMAO in healthy men and women. This reduction in TMAO production has been associated with decreasing a person's risk of heart disease.

Primary Outcome Measures: Difference in the area under the curve (AUC) of blood plasma TMAO concentrations after pomegranate extract and microcrystalline cellulose interventions., Comparison of AUC of blood plasma TMAO concentrations after L-carnitine with pomegranate extract and after L-carnitine with microcrystalline cellulose interventions., Day 2,3,4,16,17,and 18
Secondary Outcome Measures: Changes in area under the curve (AUC) from plasma concentrations of L-carnitine and its metabolites, Plasma blood concentrations of L-carnitine and its metabolites (γ-BB: γ-butyrobetaine, TMA: trimethylamine, and TMAO) will be quantified after ingestion of L-carnitine and intervention capsules (pomegranate extract or microcrystalline cellulose). AUC will be determined using trapezoidal approximation of plasma concentrations over time. Measurements will be taken 0, 0.5, 1, 1.5, 2, 2.5, 16, 18, 20, 22, 24, and 48 hours after capsules have been ingested on Day 2 and Day 16., 48 hours|Change in peak plasma concentration (Cmax) of L-carnitine and its metabolites, Plasma blood concentrations of L-carnitine and its metabolites (γ-BB: γ-butyrobetaine, TMA: trimethylamine, and TMAO) will be quantified after ingestion of L-carnitine and intervention capsules (pomegranate extract or microcrystalline cellulose). Cmax will be the highest concentration measured during a 48 hour period. Measurements will be taken 0, 0.5, 1, 1.5, 2, 2.5, 16, 18, 20, 22, 24, and 48 hours after capsules have been ingested on Day 2 and Day 16., 48 hours|Change in the time to reach peak plasma concentration (Tmax) of L-carnitine and its metabolites, Plasma blood concentrations of L-carnitine and its metabolites (γ-BB: γ-butyrobetaine, TMA: trimethylamine, and TMAO) will be quantified after ingestion of L-carnitine and intervention capsules (pomegranate extract or microcrystalline cellulose). Tmax will be the time when peak concentration of L-carnitine or its metabolites has been reached. Measurements will be taken 0, 0.5, 1, 1.5, 2, 2.5, 16, 18, 20, 22, 24, and 48 hours after capsules have been ingested on Day 2 and Day 16., 48 hours|Change in plasma half-life (t1/2) of L-carnitine and its metabolites, Plasma blood concentrations of L-carnitine and its metabolites (γ-BB: γ-butyrobetaine, TMA: trimethylamine, and TMAO) will be quantified after ingestion of L-carnitine and intervention capsules (pomegranate extract or microcrystalline cellulose). Half life will be the time point where concentration of L-carnitine or its metabolites have reduced by half. Measurements will be taken 0, 0.5, 1, 1.5, 2, 2.5, 16, 18, 20, 22, 24, and 48 hours after capsules have been ingested on Day 2 and Day 16., 48 hours|Change in the area under the curve (AUC) from urine concentrations of L-carnitine and its metabolites, Urine concentrations of L-carnitine and its metabolites (γ-BB: γ-butyrobetaine, TMA: trimethylamine, and TMAO) will be quantified after ingestion of L-carnitine and intervention capsules (pomegranate extract or microcrystalline cellulose). AUC will be determined using trapezoidal approximation of plasma concentrations over time. Measurements will be taken from urine collections at 0, 2, 2.5 to 16, 18, 20, 22, 24, and 24 to 48 hours., 48 hours|Change in pomegranate polyphenols and their metabolite concentrations from pooled 24 hour urine collections., Quantification of pomegranate polyphenols and their metabolite excretion into urine will be measured from pooled urine collections (24 and 48 hours) using targeted metabolite analysis of pomegranate polyphenols, punicalagin, ellagic acid, urolithins. These metabolites will be used to define relationships between dietary intake, pomegranate metabolism and pharmacokinetic outcomes, Day 3, 4, 17, and 18.|Difference in L-carnitine and its metabolites concentrations from faecal (stool) collections after pomegranate extract and microcrystalline cellulose interventions., Comparison in L-carnitine and and its metabolite (γ-BB: γ-butyrobetaine, TMA: trimethylamine, and TMAO) excretion into faeces (stool) will be measured from faecal samples at baseline and after each intervention period. These metabolites will be used to define relationships between dietary intake, L-carnitine metabolism and microbiome composition, Day 2, 4, and 18.|Changes in gut microbiota composition (indices of diversity and in taxonomic abundances) over study duration, Comparison of gut microbiota composition will be determined using indices of diversity and taxonomic abundances using Shotgun metagenomic sequencing of faecal samples collected at the start and end of each intervention period., Day 2, 4, 16, and 18.|Treatment effects of gut microbiota composition (indices of diversity and in taxonomic abundances) after pomegranate extract and microcrystalline cellulose interventions., Comparison of gut microbiota composition will be determined using indices of diversity and taxonomic abundances using Shotgun metagenomic sequencing of faecal samples collected at the end of each intervention period., Day 4 and 18.|Difference in bacterial transcripts from faecal (stool) collections after pomegranate extract and microcrystalline cellulose interventions., Comparison of absolute abundance of L-carnitine metabolising bacterial genes and their transcripts using specific qPCR (quantitative polymerase chain reaction) and RT-qPCR (Real-time polymerase chain reaction) assays from faecal samples collected at baseline and after each intervention period., Day 2, 4, and 18.|Correlation between plasma TMAO concentration and quantity of L carnitine-rich foods consumed in habitual diets of healthy men and women., Plasma TMAO concentration measured during the first phase of this study will be correlated (Pearson correlation) with the quantity of L-carnitine-rich foods collected from a 90-day Food Frequency Questionnaire (VioCare VioScreen)., Phase 1 Day 2