Ignite Creation Date:
2024-05-06 @ 6:02 PM
Last Modification Date:
2024-10-26 @ 2:40 PM
Study NCT ID:
NCT05529953
Status:
COMPLETED
Last Update Posted:
2022-10-31
First Post:
2022-09-02
Brief Title:
Bioavailability of Oleanolic Acid Formulated as Functional Olive Oil
Sponsor:
Spanish National Research Council
Organization:
Spanish National Research Council
Study Overview
Official Title:
Bioavailability Assays of Oleanolic Acid Formulated as Functional Olive Oil in Healthy Subjects Pharmacokinetic Analysis and Study of Its Integration in Postprandial Human Triglyceride-Rich Lipoproteins
Status:
COMPLETED
Status Verified Date:
2022-10
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:
BIO-OLTRAD
Brief Summary:
The oral bioavailability of Oleanolic acid OA when formulated as functional olive oil and its mechanisms of systemic transport will be approached by mean of randomized and controlled trial with 20 healthy volunteers Ten individuals randomly selected will receive 55 mL of the functional OA-enriched olive oil equivalent dose 30 mg OA as part of an experimental breakfast The other ten participants will receive within this experimental meal the same amount of the control olive oil Immediately before and after eating the respective breakfasts aliquots of cubital blood will be drawn every hour over a postprandial period of 7 hours Since in this trial design each participant is hisher own control a four-week washout period is established after which a new series of tests that cross the type of olive oil consumed will be carried out
From the aliquots of cubital blood sera will be obtained by centrifugation The extraction and quantification of serum OA will be realized by gas chromatography GC using flame ionization FID and mass spectrometry MS detectors In the pharmacokinetic analysis of data a mono-compartmental model will be assumed It will be determined 1 absorption parameters such as the maximum concentration achieved and the timing for it the constant of absorption and the area under the curve 2 distribution parameters such as the constant and volume of distribution 3 metabolism parameters such as the OA fraction associated with albumin and 4 elimination parameters such as the elimination constant the half-life and the clearance
To demonstrate the presence of OA in postprandial TRL chylomicron and VLDL fractions will be prepared by plasma ultrafiltration in normal saline and hydrolysed with pancreatic enzyme The possible presence of OA among the TRL-derived lipids will be evaluated The content of apo B48 and B100 as markers of the presence of chylomicrons and VLDL respectively will be determined by ELISA
Other parameters related to glycemic control such as serum insulin C-peptide and GLP-1 will be analyzed by ELISA
From the aliquots of cubital blood sera will be obtained by centrifugation The extraction and quantification of serum OA will be realized by gas chromatography GC using flame ionization FID and mass spectrometry MS detectors In the pharmacokinetic analysis of data a mono-compartmental model will be assumed It will be determined 1 absorption parameters such as the maximum concentration achieved and the timing for it the constant of absorption and the area under the curve 2 distribution parameters such as the constant and volume of distribution 3 metabolism parameters such as the OA fraction associated with albumin and 4 elimination parameters such as the elimination constant the half-life and the clearance
To demonstrate the presence of OA in postprandial TRL chylomicron and VLDL fractions will be prepared by plasma ultrafiltration in normal saline and hydrolysed with pancreatic enzyme The possible presence of OA among the TRL-derived lipids will be evaluated The content of apo B48 and B100 as markers of the presence of chylomicrons and VLDL respectively will be determined by ELISA
Other parameters related to glycemic control such as serum insulin C-peptide and GLP-1 will be analyzed by ELISA
Detailed Description:
Design and implementation of the biovailability assays The study of oral bioavailability of Oleanolic acid OA when formulated as functional olive oil and its mechanisms of systemic transport will be approached by mean of a postprandial intervention with 20 healthy volunteers
The participants will be recruited after the complete biochemical and hematological analysis yield results within normal limits and after checking in their electronic medical histories that they do not suffer from digestive metabolic or oncologic disorders or any other pathology that in opinion of the clinical investigators could prevent them from participating in the trial For their inclusion in the trial it is also required that they grant the written consent to the protocols approved by the Institutional Committees for Human Research after being conveniently informed both orally and documentally
The fieldwork will be performed in the Day Hospital of the Endocrinology and Nutrition Service of the University Hospitals Virgen del Rocio from Seville SPAIN
Sample size The main quantitative variable to be examined in this trial is OA serum concentration In the absence of consistent baseline data published so far data from the analysis of OA in sera of the PREDIABOLE Study ISRCTN03372660 have been used A cohort of 25 participants from the control group consuming commercial olive oil was selected and an average baseline concentration of 155 72 ng OAmL was determined Considering this it is now postulated that the plasma OA content will increase by at least 50 as consequence of the intake of the functional olive oil equivalent dose 30 mg OA To prove this unilateral hypothesis test with a confidence level of 90 risk α001 zα1645 and a power of 95 zβ1645 a sample size of at least 17 volunteers is required Assuming that losses lower than 15 are tolerable the adjusted sample size would be 20 subjects
Anamnesis and physical examination of participants The anamnesis will include vital data and general history collecting all the symptoms that the individual may present their medical and surgical history as well as pharmacological treatments followed Information about lifestyle perception of the own body image diet and kind and intensity of physical activity will be also obtained In addition the muscle mass fatty compartment adipose panniculus existence of edema etc will be examined Likewise systolic and diastolic blood pressure and heart rate will be determined
Anthropometric study and body composition The anthropometric study will include the determination of total body weight height body mass index BMI as well as waist and hip circumferences The study and evaluation of these variables will be carried out in accordance with the guidelines of the International Society for the Advancement of kinanthropometry ISAK The study of body composition will be carried out by electrical bioimpedance using a TANITA body composition analyzer model BC-418MA Fat mass lean mass muscle mass total water bone mass basal metabolism and visceral fat will be quantified with this technique making use of prediction equations validated and adjusted by age and sex
Biochemical studies Samples of fasting cubital blood will be drawn to determine the parameters of general hepatic and renal biochemistry In addition a complete urine analysis will be performed which include the habitual physical chemical and microscopically measurements These determinations will be carried out at the Laboratory of Analysis and Clinical Biochemistry of Virgen del Rocío University Hospitals of Seville
Intervention The participants will be encouraged to avoid the consumption of alcoholic beverages and tobacco during the day preceding the execution of the assays On trial days and after 12 hours of overnight fasting blood samples will be drawn from the cubital vein Subsequently ten individuals randomly selected will receive 55 mL of the functional OA-enriched olive oil equivalent dose 30 mg OA as part of an experimental breakfast that includes coffee skimmed milk and whole-grain toast The other ten participants will receive within the experimental meal the same amount of the control olive oil After eating the respective breakfasts aliquots of cubital blood will be drawn every hour over a postprandial period of 7 hours During this time free access to water intake will be allowed
A four-week washout period is established after which a new series of tests that cross the type of olive oil consumed will be carried out
Pharmacokinetic study of OA From the aliquots of cubital blood sera will be obtained by centrifugation and NaN3 PMSF and aprotinin will be added as preservatives to avoid their proteolytic degradation Serum samples will be stored at -80 0C in the laboratories of the IG-CSIC until analysis The extraction and fractionation of serum OA will be realized by liquidliquid and solid phase extractions whereas the identification and quantification of the triterpene will be completed by GC-FID and GC-MS In the pharmacokinetic analysis of data a mono-compartmental model will be assumed From data of the serum contents of free OA throughout the postprandial period the following parameters will be determined 1 absorption parameters such as the maximum concentration achieved and the timing for it the constant of absorption and the area under the curve 2 distribution parameters such as the constant and volume of distribution 3 metabolism parameters such as the OA fraction associated with albumin and 4 elimination parameters such as the elimination constant the half-life and the clearance For calculations the SigmaPLot pharmacokinetic analysis module Systat Software Inc San Jose CA USA will be used
Study of the presence of OA in triglyceride rich lipoproteins TRL Chylomicrons will be first isolated from plasma in normal saline by centrifugation at 100000 g for 20 min Very low density lipoproteins VLDL will be subsequently separated at 230000 g for 18 h The chylomicron and VLDL fractions will be hydrolyzed with pancreatic enzyme The released lipids will be extracted with chloroformmethanol 21 and fractionated by solidliquid extraction with methanolchloroform 11 and isopropanolacetonitrilewater 211 The free fatty acids FFA composition will be analysed by GC-FID as the correspondent methyl esters The possible presence of OA among the TRL-derived lipids will be evaluated after fractionation and GC-MS analysis The content of apo B48 and B100 as markers of the presence of chylomicrons and VLDL respectively will be determined by ELISA
Other biochemical parameters serum insulin C-peptide and GLP-1 will be analyzed by ELISA
The participants will be recruited after the complete biochemical and hematological analysis yield results within normal limits and after checking in their electronic medical histories that they do not suffer from digestive metabolic or oncologic disorders or any other pathology that in opinion of the clinical investigators could prevent them from participating in the trial For their inclusion in the trial it is also required that they grant the written consent to the protocols approved by the Institutional Committees for Human Research after being conveniently informed both orally and documentally
The fieldwork will be performed in the Day Hospital of the Endocrinology and Nutrition Service of the University Hospitals Virgen del Rocio from Seville SPAIN
Sample size The main quantitative variable to be examined in this trial is OA serum concentration In the absence of consistent baseline data published so far data from the analysis of OA in sera of the PREDIABOLE Study ISRCTN03372660 have been used A cohort of 25 participants from the control group consuming commercial olive oil was selected and an average baseline concentration of 155 72 ng OAmL was determined Considering this it is now postulated that the plasma OA content will increase by at least 50 as consequence of the intake of the functional olive oil equivalent dose 30 mg OA To prove this unilateral hypothesis test with a confidence level of 90 risk α001 zα1645 and a power of 95 zβ1645 a sample size of at least 17 volunteers is required Assuming that losses lower than 15 are tolerable the adjusted sample size would be 20 subjects
Anamnesis and physical examination of participants The anamnesis will include vital data and general history collecting all the symptoms that the individual may present their medical and surgical history as well as pharmacological treatments followed Information about lifestyle perception of the own body image diet and kind and intensity of physical activity will be also obtained In addition the muscle mass fatty compartment adipose panniculus existence of edema etc will be examined Likewise systolic and diastolic blood pressure and heart rate will be determined
Anthropometric study and body composition The anthropometric study will include the determination of total body weight height body mass index BMI as well as waist and hip circumferences The study and evaluation of these variables will be carried out in accordance with the guidelines of the International Society for the Advancement of kinanthropometry ISAK The study of body composition will be carried out by electrical bioimpedance using a TANITA body composition analyzer model BC-418MA Fat mass lean mass muscle mass total water bone mass basal metabolism and visceral fat will be quantified with this technique making use of prediction equations validated and adjusted by age and sex
Biochemical studies Samples of fasting cubital blood will be drawn to determine the parameters of general hepatic and renal biochemistry In addition a complete urine analysis will be performed which include the habitual physical chemical and microscopically measurements These determinations will be carried out at the Laboratory of Analysis and Clinical Biochemistry of Virgen del Rocío University Hospitals of Seville
Intervention The participants will be encouraged to avoid the consumption of alcoholic beverages and tobacco during the day preceding the execution of the assays On trial days and after 12 hours of overnight fasting blood samples will be drawn from the cubital vein Subsequently ten individuals randomly selected will receive 55 mL of the functional OA-enriched olive oil equivalent dose 30 mg OA as part of an experimental breakfast that includes coffee skimmed milk and whole-grain toast The other ten participants will receive within the experimental meal the same amount of the control olive oil After eating the respective breakfasts aliquots of cubital blood will be drawn every hour over a postprandial period of 7 hours During this time free access to water intake will be allowed
A four-week washout period is established after which a new series of tests that cross the type of olive oil consumed will be carried out
Pharmacokinetic study of OA From the aliquots of cubital blood sera will be obtained by centrifugation and NaN3 PMSF and aprotinin will be added as preservatives to avoid their proteolytic degradation Serum samples will be stored at -80 0C in the laboratories of the IG-CSIC until analysis The extraction and fractionation of serum OA will be realized by liquidliquid and solid phase extractions whereas the identification and quantification of the triterpene will be completed by GC-FID and GC-MS In the pharmacokinetic analysis of data a mono-compartmental model will be assumed From data of the serum contents of free OA throughout the postprandial period the following parameters will be determined 1 absorption parameters such as the maximum concentration achieved and the timing for it the constant of absorption and the area under the curve 2 distribution parameters such as the constant and volume of distribution 3 metabolism parameters such as the OA fraction associated with albumin and 4 elimination parameters such as the elimination constant the half-life and the clearance For calculations the SigmaPLot pharmacokinetic analysis module Systat Software Inc San Jose CA USA will be used
Study of the presence of OA in triglyceride rich lipoproteins TRL Chylomicrons will be first isolated from plasma in normal saline by centrifugation at 100000 g for 20 min Very low density lipoproteins VLDL will be subsequently separated at 230000 g for 18 h The chylomicron and VLDL fractions will be hydrolyzed with pancreatic enzyme The released lipids will be extracted with chloroformmethanol 21 and fractionated by solidliquid extraction with methanolchloroform 11 and isopropanolacetonitrilewater 211 The free fatty acids FFA composition will be analysed by GC-FID as the correspondent methyl esters The possible presence of OA among the TRL-derived lipids will be evaluated after fractionation and GC-MS analysis The content of apo B48 and B100 as markers of the presence of chylomicrons and VLDL respectively will be determined by ELISA
Other biochemical parameters serum insulin C-peptide and GLP-1 will be analyzed by ELISA
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| PID2019-107837RB-100 | OTHER_GRANT | Spanish National Research Agency | None |