Ignite Creation Date:
2024-05-06 @ 7:29 PM
Last Modification Date:
2024-10-26 @ 3:07 PM
Study NCT ID:
NCT06028659
Status:
RECRUITING
Last Update Posted:
2024-03-08
First Post:
2023-08-23
Brief Title:
Investigation of in Vivo Endogenous andor Exogenous Production of Phenolic Metabolites Using unTargeted Metabolomics
Sponsor:
University of Parma
Organization:
University of Parma
Study Overview
Official Title:
Investigation of in Vivo Endogenous andor Exogenous Production of Phenolic Metabolites Using unTargeted Metabolomics
Status:
RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ENDOPHENOL
Brief Summary:
Plant polyphenols is what we call a large number of substances that are produced by plants as secondary plant metabolites which means substances that are not used for their growth and development but are necessary for them to survive Polyphenols are divided in two major groups flavonoids and non-flavonoids and each group contains a varied set of subgroups and substances They are widely spread in fruit and vegetables that are part of the human diet and in general studies have attributed many biological effects to the ingestion of polyphenols especially in the prevention of non-communicable diseases For this reason research aims to understand their role in the health benefits of a diet that is rich in fruits and vegetables When ingested polyphenols are digested by both the human organism and the gut microbiota and are broken down into several smaller substances catabolites that are called low-molecular weight polyphenols LMWP Most of the absorbed polyphenols that reach our bloodstream and organs are LMWP
For the proposed study 30 healthy adults will be recruited and if considered able to participate will follow a standardized diet that is restricted in polyphenol intake and will be randomly divided into two groups one will receive a known source of polyphenols coffee and the other will receive water keeping the restriction of polyphenol from the diet The duration of one phase is 4 days 12 hours during which urine feces and saliva will be collected Then after a 2-week-interval subjects will repeat the experiment except that this time the group who had coffee will have water and vice versa Again urine and feces will be collected The objective of the study is to identify and quantify LMWP mainly in urine but also in feces and try to understand how much was produced when there was no polyphenols in the diet compared with when there was ingestion of coffee polyphenols The production of LMWP without coffee could be because of their production from other sources like the metabolism of amino acids proteins and catecholamines ie dopamine The composition of the gut microbiota and relevant genetic information can alter the metabolism of polyphenols and will be considered in the analyses Knowing how much of LMWP actually comes from the diet is important to understand the relevance and health benefits of these molecules
For the proposed study 30 healthy adults will be recruited and if considered able to participate will follow a standardized diet that is restricted in polyphenol intake and will be randomly divided into two groups one will receive a known source of polyphenols coffee and the other will receive water keeping the restriction of polyphenol from the diet The duration of one phase is 4 days 12 hours during which urine feces and saliva will be collected Then after a 2-week-interval subjects will repeat the experiment except that this time the group who had coffee will have water and vice versa Again urine and feces will be collected The objective of the study is to identify and quantify LMWP mainly in urine but also in feces and try to understand how much was produced when there was no polyphenols in the diet compared with when there was ingestion of coffee polyphenols The production of LMWP without coffee could be because of their production from other sources like the metabolism of amino acids proteins and catecholamines ie dopamine The composition of the gut microbiota and relevant genetic information can alter the metabolism of polyphenols and will be considered in the analyses Knowing how much of LMWP actually comes from the diet is important to understand the relevance and health benefits of these molecules
Detailed Description:
The study will consist of a randomized cross-over trial and each arm will last 5 days A total of thirty 30 healthy volunteers will be recruited for the study in Parma PR using announcements placed in the university hospital and public places To allocate subjects to each arm a list will be generated using a randomized block design by using Random Number Generator Pro Segobit Software This list will be blind for the PI and volunteers as it will be made by a colleague not involved in the subjects enrolment and using a numbered sequence in sealed opaque envelopes
Volunteers freely accepting to participate to the study will be asked for their written informed consent Information to the volunteers will be provided before and separately from the consent form These information sheets and the informed consent forms have been prepared according to the Oviedo Convention and consider the guide of the local Ethics Committee After obtaining their written informed consent volunteers will undergo a screening visit to determine eligibility and collect personal data
Privacy of the volunteers will be assured through pseudoanonymization by the attribution of a personal alphanumeric code Recruited volunteers will also sign an authorisation to the use of personal information and retrieved data
After recruitment subjects will attend a first visit when personal data will be collected and body composition and anthropometry parameters measured Then they will receive the foods supplements and materials necessary to follow the study The recruited subjects will be requested to follow a low-polyphenol diet which will be the same for all the volunteers and maintained for the whole period of the intervention study The foods preparation mode and times for eating the meals will be provided by the sponsor The diet will be personalised to approximate the necessary calories based on the measured basal metabolic rate multiplied by the physical activity level set at 145 and there will be quantitative variations on the low-polyphenol diet based on the daily energy requirement 1500 kcalday 1750 kcalday 2000 kcalday 2250 kcalday 2500 kcalday 2750 kcalday or 3000 kcalday all with nutritionally balanced amounts of protein fat and carbohydrates In addition participants will be requested to restrict physical exercise during the study duration
Subjects will be asked to collect urine produced during the 60h prior the intervention starting from the evening prior the first day of diet from 2100 of the night prior the first day of diet and every 12 hours 60-48h 48-36h 36-24h 24-12h 12-0h and to complete the food diary to check for compliance to the diet Subjects are asked to bring collected urine to the the Human Nutrition Unit of the Food and Drug Department of the University of Parma
On the morning of the third day of diet subjects will be requested to arrive at Parma University in fasting conditions Prior to receiving the intervention fasting spot urine and saliva samples will be collected Then sugared-decaffeinated-coffee 3 doses of 50 mL each and 5g of sugar or sugared-water 150 mL of water and 5g of sugar will be provided according to randomization of the arms along with a standardized breakfast consisting of a polyphenol-free nutritionally balanced solid meal and water ad libitum
After breakfast subjects will be asked to autonomously collect urine for the next 48h at specified timepoints 0 - 3h 3 - 6h 6 - 9h 9 - 12h 12 - 24h 24 - 36h and 36 - 48h following the same personalized diet Lastly subjects will autonomously collect a fecal sample within 6 to 48h after the intervention
On the morning of the last day after the last urine collection subjects will bring collected urine and fecal samples and the 5-day food diary to the Human Nutrition Unit of the Food and Drug Department of the University of Parma
After the first arm subjects will resume their habitual lifestyles for 2 consecutive weeks subsequently they will attend another visit when all the anthropometric evaluations carried out during the first visit will be repeated and another kit with foods and information for the personalized diet will be given With the study being a cross-over design the protocol followed will be the same as the one described above except for saliva sampling which will only be performed once Coming the third day of diet subjects who ingested coffee in the prior arm of the study will ingest water and vice-versa
For this study the sample size was estimated considering the mean concentration of coffee-derived polyphenols and their metabolites in urine as the primary outcome and the available literature on similar approaches and studies of the area The number of 30 volunteers was established considering the accepted parameters for clinical trials power set at 08 and α set at 005 possible dropouts 15 drop-out rate and exclusion of volunteers to maintain the sample power for statistical analysis Before any comparison is performed the normality of each variable will be evaluated to choose the most appropriate statistical test If metabolite data are normally distributed data will be expressed as mean standard deviation and analysed using repeated measures t-test or ANOVA with post-hoc comparisons If data are not normally distributed they will be reported as median and Interquartile Range and the Friedman test with post hoc pairwise comparisons will be performed P-value 005 will be regarded as statistically significant
Unsupervised and supervised multivariate analysis will be used to identify and characterize the different urinary metabotypes following the procedures developed by our research group for targeted metabolomics analysis of phenolic metabolites or when using untargeted metabolomics data We will be using different clustering approaches to better explore the existing variability This will serve to establish the number of clusters ie phenolic metabotypes the number of participants forming each cluster and the similarities among possible metabotypes
The relationship between patterns of LMWP and their putative determinants age sex ethnicity lifestyle anthropometrics body composition genotype and gut microbiome will be explored using correlation tests and multivariate analyses P-value 005 will be regarded as statistically significant Statistics will be carried out by the specialized staff of the Human Nutrition Unit under the supervision of the PI and in collaboration with the University teams in charge of microbial profiling and genotyping
Volunteers freely accepting to participate to the study will be asked for their written informed consent Information to the volunteers will be provided before and separately from the consent form These information sheets and the informed consent forms have been prepared according to the Oviedo Convention and consider the guide of the local Ethics Committee After obtaining their written informed consent volunteers will undergo a screening visit to determine eligibility and collect personal data
Privacy of the volunteers will be assured through pseudoanonymization by the attribution of a personal alphanumeric code Recruited volunteers will also sign an authorisation to the use of personal information and retrieved data
After recruitment subjects will attend a first visit when personal data will be collected and body composition and anthropometry parameters measured Then they will receive the foods supplements and materials necessary to follow the study The recruited subjects will be requested to follow a low-polyphenol diet which will be the same for all the volunteers and maintained for the whole period of the intervention study The foods preparation mode and times for eating the meals will be provided by the sponsor The diet will be personalised to approximate the necessary calories based on the measured basal metabolic rate multiplied by the physical activity level set at 145 and there will be quantitative variations on the low-polyphenol diet based on the daily energy requirement 1500 kcalday 1750 kcalday 2000 kcalday 2250 kcalday 2500 kcalday 2750 kcalday or 3000 kcalday all with nutritionally balanced amounts of protein fat and carbohydrates In addition participants will be requested to restrict physical exercise during the study duration
Subjects will be asked to collect urine produced during the 60h prior the intervention starting from the evening prior the first day of diet from 2100 of the night prior the first day of diet and every 12 hours 60-48h 48-36h 36-24h 24-12h 12-0h and to complete the food diary to check for compliance to the diet Subjects are asked to bring collected urine to the the Human Nutrition Unit of the Food and Drug Department of the University of Parma
On the morning of the third day of diet subjects will be requested to arrive at Parma University in fasting conditions Prior to receiving the intervention fasting spot urine and saliva samples will be collected Then sugared-decaffeinated-coffee 3 doses of 50 mL each and 5g of sugar or sugared-water 150 mL of water and 5g of sugar will be provided according to randomization of the arms along with a standardized breakfast consisting of a polyphenol-free nutritionally balanced solid meal and water ad libitum
After breakfast subjects will be asked to autonomously collect urine for the next 48h at specified timepoints 0 - 3h 3 - 6h 6 - 9h 9 - 12h 12 - 24h 24 - 36h and 36 - 48h following the same personalized diet Lastly subjects will autonomously collect a fecal sample within 6 to 48h after the intervention
On the morning of the last day after the last urine collection subjects will bring collected urine and fecal samples and the 5-day food diary to the Human Nutrition Unit of the Food and Drug Department of the University of Parma
After the first arm subjects will resume their habitual lifestyles for 2 consecutive weeks subsequently they will attend another visit when all the anthropometric evaluations carried out during the first visit will be repeated and another kit with foods and information for the personalized diet will be given With the study being a cross-over design the protocol followed will be the same as the one described above except for saliva sampling which will only be performed once Coming the third day of diet subjects who ingested coffee in the prior arm of the study will ingest water and vice-versa
For this study the sample size was estimated considering the mean concentration of coffee-derived polyphenols and their metabolites in urine as the primary outcome and the available literature on similar approaches and studies of the area The number of 30 volunteers was established considering the accepted parameters for clinical trials power set at 08 and α set at 005 possible dropouts 15 drop-out rate and exclusion of volunteers to maintain the sample power for statistical analysis Before any comparison is performed the normality of each variable will be evaluated to choose the most appropriate statistical test If metabolite data are normally distributed data will be expressed as mean standard deviation and analysed using repeated measures t-test or ANOVA with post-hoc comparisons If data are not normally distributed they will be reported as median and Interquartile Range and the Friedman test with post hoc pairwise comparisons will be performed P-value 005 will be regarded as statistically significant
Unsupervised and supervised multivariate analysis will be used to identify and characterize the different urinary metabotypes following the procedures developed by our research group for targeted metabolomics analysis of phenolic metabolites or when using untargeted metabolomics data We will be using different clustering approaches to better explore the existing variability This will serve to establish the number of clusters ie phenolic metabotypes the number of participants forming each cluster and the similarities among possible metabotypes
The relationship between patterns of LMWP and their putative determinants age sex ethnicity lifestyle anthropometrics body composition genotype and gut microbiome will be explored using correlation tests and multivariate analyses P-value 005 will be regarded as statistically significant Statistics will be carried out by the specialized staff of the Human Nutrition Unit under the supervision of the PI and in collaboration with the University teams in charge of microbial profiling and genotyping
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None