Clinical trial NCT03621865: A Comparative Pharmacokinetic Study to Evaluate the Ability of a New Formulation to Enhance Curcuminoids Bioavailability
Official title: A Comparative Pharmacokinetic Study in Healthy Volunteers to Evaluate the Ability of TURMIPURE GOLD Formulation to Enhance the Bioavailability of Curcuminoids
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: bioavailability
pharmacokinetic study
curcuminoids
curcumin
healthy volunteers
Lead sponsor: Givaudan France Naturals
Sponsor class: INDUSTRY
Collaborators: name: Biofortis Mérieux NutriSciences
First posted: 2018-08-09
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This pharmacokinectic study is designed as a monocentric, randomized, cross-over, pilot and open clinical trial
Primary purpose: BASIC_SCIENCE

Brief summary: The rhizome of Curcuma longa (turmeric) is commonly used as a spice and for its medicinal properties traditionally in Asian countries. Turmeric extract usually contains 95% curcuminoids with a specific ratio (approximately 75-80% curcumin, 15-20% demethoxycurcumin (DMC), and 0-10% bisdemethoxycurcumin (BDMC)).

Curcuminoids have higher solubility in organic solvents than in water. As a consequence, curcuminoids have low aqueous solubility and poor gastrointestinal absorption. They also exhibit rapid metabolism and systemic elimination and are therefore known to have limited bioavailability, which limits the use of turmeric extract in general health care and as an adjunct in managing various diseases. In order to improve the bioavailability of curcumin, several approaches have been undertaken. The use of adjuvant like piperine that interferes with glucuronidation; liposomal curcumin, nanoparticles, phospholipid complex; and structural analogues of curcumin.

Recently, Naturex has developed a dried emulsion formulation using a turmeric extract mixed together with a quillaja extract, sunflower oil and arabic gum. This formulation is highly dispersible in water and should therefore improve the bioavailability of curcuminoids. The aim of this study is to assess the bioavailability of curcuminoids and their metabolites after oral intake of 4 turmeric extract-based formulations in comparison to a standard unformulated turmeric extract.

Detailed description: The rhizome of Curcuma longa (turmeric) is commonly used as a spice and for its medicinal proprieties traditionally in Asian countries. Turmeric has been studying in different therapeutic areas. Antioxidant, anti-inflammatory (respiratory system, joints and digestive), antimutagenic, antimicrobial, neurological disease, hepatoprotective and anticancer properties are supported by in vitro and in vivo data.

Curcumin has been studied as the main bioactive component of turmeric associated to its potential health effect. However, besides curcumin, others components have been identified (demethoxycurcumin DMC and bisdemethoxycurcumin BDMC); this group of coumpounds are named together "curcuminoids". Curcuminoids are natural yellow-orange pigments and hydrophobic polyphenols derived from the rhizome of the herb Curcuma longa. They are commonly isolated from the spice and food-coloring agent turmeric. Extracts of turmeric generally contain 75-80% curcumin, 15-20% DMC, and 0-10% BDMC. Regarding the intrinsic property, curcuminoids have higher solubility in organic solvents than in water. As a consequence, curcuminoids have low aqueous solubility and poor gastrointestinal absorption. They also exhibit rapid metabolism and systemic elimination.

This leads to the conclusion that curcuminoids from turmeric extract have low bioavailability, which limits its use in general health care and as an adjunct in managing various diseases. In order to improve the bioavailability of curcumin, several approaches have been undertaken. The use of adjuvant like piperine that interferes with glucuronidation; liposomal curcumin, nanoparticles, phospholipid complex; and structural analogues of curcumin.

Recently, Naturex has developed a dried emulsion formulation using a turmeric extract mixed together with a quillaja extract, sunflower oil and arabic gum. This formulation is highly dispersible in water and should therefore improve the bioavailability of curcuminoids. The aim of this study is to assess the bioavailability of curcuminoids and their metabolites after oral intake of 4 turmeric extract-based formulations in comparison to a standard unformulated turmeric extract.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 45 years (limits included),
* BMI between 19 and 25 kg/m² (limits included),
* Weight stable within ±3kg in the last three months,
* With routine blood chemistry values within the normal range
* For women: Non menopausal with the same reliable contraception since at least 3 cycles before the beginning of the study and agreeing to keep it during the entire duration of the study (condom with spermicidal gel and estrogen/progestin combination contraception accepted) or menopausal without or with hormone replacement therapy (estrogenic replacement therapy begun from less than 3 months excluded),
* Non smoking or with tobacco consumption ≤ 5 cigarettes / day and agreeing not to smoke during all experimental sessions (V1 to V5),
* Agreeing not to consume food, drink and condiment containing curcumin, turmeric (curcuma longa Linn.) or curry for 1 week prior to and throughout the entire study,
* Good general and mental health with in the opinion of the investigator: no clinically significant and relevant abnormalities of medical history or physical examination,
* Able and willing to participate to the study by complying with the protocol procedures as evidenced by his dated and signed informed consent form,
* Affiliated with a social security scheme,
* Agreeing to be registered on the volunteers in biomedical research file

Exclusion Criteria:

* Suffering from a metabolic or endocrine disorder such as diabetes, uncontrolled or controlled thyroidal trouble or other metabolic disorder,
* Suffering from a severe chronic disease (e.g. cancer, HIV, renal failure, ongoing hepatic or biliary disorders, chronic inflammatory digestive disease, arthritis or other chronic respiratory trouble, etc.) or gastrointestinal disorders found to be inconsistent with the conduct of the study by the investigator (e.g. celiac disease),
* Suffering from liver diseases
* Current disease states that are contraindicated to subjects with dietary supplementation: chronic diarrhea, constipation or abdominal pain, Inflammatory bowel diseases (Crohn's disease or ulcerative colitis), Cirrhosis, chronic laxatives use...,
* Suffering from Irritable Bowel Syndrome (IBS) diagnosed by a medical doctor and treated with chronic medication,
* Having medical history of current pathology which could affect the study results or expose the subject to an additional risk according to the investigator,
* Recent gastroenteritis or food borne illness such as confirmed food poisoning (less than 1 month),
* Who made a blood donation in the 3 months before the V0 visit or intending to make it within 3 months ahead,
* With a low venous capital not allowing to perform kinetic of blood samples according to the investigator's opinion,
* With a known or suspected food allergy or intolerance or hypersensitivity to any of the study products' ingredient and/or of the standard meals (gluten intolerance, celiac disease, etc....)
* Pregnant or lactating women or intending to become pregnant within 3 months ahead,
* Exhibiting alcohol or drug dependence
* On any chronic drug treatment (for example anticoagulant, antihypertensive treatment, treatment thyroid, asthma treatment, anxiolytic, antidepressant, lipid-lowering treatment, corticosteroids, phlebotonic, veino-tonic, drug with impact on blood circulation ...) excepting oral and local contraceptives,
* Currently taking (and during the past 3 months) any supplementation from botanical origins
* Having consumed curcumin-containing food supplements (curcumin, turmeric and curry) or foods (curcumin, turmeric, E100, and curry) defined as at least 3 times per week and for 2 weeks prior to testing
* Currently taking (and during the past 3 months) any prebiotics or probiotics supplementation from food or from dietary supplements
* With significant change in food habits or in physical activity in the 3 months before the V0 visit or not agreeing to keep them unchanged throughout the study,
* Trying to lose weight with a current or planned in the next 3 months specific diet (hyper or hypocaloric, vegan, vegetarian...) or exercice regimen
* With a personal history of anorexia nervosa, bulimia or significant eating disorders according to the investigator,
* Consuming more than 3 standard drinks of alcoholic beverage daily for men or 2 daily for women or not agreeing to keep his alcohol consumption habits unchanged throughout the study,
* Having a lifestyle deemed incompatible with the study according to the investigator including high level physical activity (defined as more than 10 hours of significant physical activity a week, walking excluded),
* Taking part in another clinical trial or being in the exclusion period of a previous clinical trial,
* Having received, during the last 12 months, indemnities for clinical trial higher or equal to 4500 Euros,
* Under legal protection (guardianship, wardship) or deprived from his rights following administrative or judicial decision,
* Presenting a psychological or linguistic incapability to sign the informed consent,
* Impossible to contact in case of emergency.

After V0 biological analyses the subject will be considered as non-eligible to the study on the following criteria:

- Control record (Glycaemia, GGT, ASAT, ALAT, Urea, Creatinine and Complete blood count) with clinically significant abnormality according to the investigator

Primary outcomes:
measure: Dose-normalized AUC of total curcuminoids plasmatic concentration
timeFrame: from 0 to 24 hours
Secondary outcomes:
measure: AUC of total curcuminoids plasmatic concentration
timeFrame: from 0 to 24 hours
measure: AUC of curcuminoids separately (curcumin, DMC, BDMC) plasmatic concentrations
timeFrame: from 0 to 24 hours
measure: AUC of curcuminoids metabolites plasmatic concentrations
timeFrame: from 0 to 24 hours
measure: AUC of total curcuminoids plasmatic concentration normalized to curcuminoids intake
timeFrame: from 0 to 8 hours
measure: AUC of total curcuminoids plasmatic concentration
timeFrame: from 0 to 8 hours
measure: AUC of curcuminoids separately (curcumin, DMC, BDMC) plasmatic concentrations
timeFrame: from 0 to 8 hours
measure: AUC of curcuminoids metabolites plasmatic concentrations
timeFrame: from 0 to 8 hours
measure: AUC of total curcuminoids plasmatic concentration normalized to curcuminoids intake
timeFrame: from 0 to infinity
measure: AUC of total curcuminoids plasmatic concentration
timeFrame: from 0 to infinity
measure: AUC of curcuminoids separately (curcumin, DMC, BDMC) plasmatic concentrations
timeFrame: from 0 to infinity
measure: AUC of curcuminoids metabolites plasmatic concentrations
timeFrame: from 0 to infinity
measure: Peak of total curcuminoids plasmatic concentration normalized to curcuminoids intake
timeFrame: 24hours
measure: Peak of total curcuminoids plasmatic concentration
timeFrame: 24hours
measure: Peak of curcuminoids separately plasmatic concentrations
timeFrame: 24hours
measure: Peak of curcuminoids metabolites plasmatic concentrations
timeFrame: 24hours
measure: Half-life of total curcuminoids in plasma
timeFrame: 24hours
measure: Half-life of curcuminoids separately (curcumin, DMC, BDMC) in plasma
timeFrame: 24hours
measure: Half-life of curcuminoids metabolites in plasma
timeFrame: 24hours
measure: Terminal elimination rate constant of total curcuminoids in plasma (λz)
timeFrame: 24hours
measure: Terminal elimination rate constant curcuminoids separately (curcumin, DMC, BDMC) in plasma (λz)
timeFrame: 24hours
measure: Terminal elimination rate constant curcuminoids metabolites in plasma (λz)
timeFrame: 24hours
measure: Time to peak of total curcuminoids plasmatic concentrations
timeFrame: 24hours
measure: Time to peak of curcuminoids separately (curcumin, DMC, BDMC) plasmatic concentrations
timeFrame: 24hours
measure: Time to peak of curcuminoids metabolites plasmatic concentrations
timeFrame: 24hours
measure: Relative bioavailability
timeFrame: from 0 to 24 hours
Other outcomes:
Locations:
city: Saint-Herblain
country: France
facility: Biofortis Mérieux NutriSciences
Study officials:
affiliation: Naturex
name: Pascale Fança-Berthon, PhD
role: STUDY_DIRECTOR
References:
citation: Fanca-Berthon P, Tenon M, Bouter-Banon SL, Manfre A, Maudet C, Dion A, Chevallier H, Laval J, van Breemen RB. Pharmacokinetics of a Single Dose of Turmeric Curcuminoids Depends on Formulation: Results of a Human Crossover Study. J Nutr. 2021 Jul 1;151(7):1802-1816. doi: 10.1093/jn/nxab087.