Clinical trial NCT05699473: Bioavailability Study of Folate in Healthy Subjects
Official title: A Double Blind, Randomized, Cross-over, Comparative Bioavailability Study of 3 Different Forms of Folate in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Healthy
Keywords: folate
bioavailability
comparative study
single dose
Lead sponsor: Lesaffre International
Sponsor class: INDUSTRY
Collaborators: name: BioFortis
name: Soladis
First posted: 2023-01-26
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Prospective, monocentric, double-blind, randomized, cross-over bioavailability study
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of this prospective interventional study is to compare the bioavailability of the 6S-5-methyltetrahydrofolate (5-MTHF) glucosamine salt versus two other forms of 5- MTHF calcium salts by measuring serum 5-MTHF responses after a single ingestion of equivalent doses of the three folate forms in humans.

The hypothesis of this study is that the test products 5-MTHF glucosamine and calcium salts have equivalent bioavailabilities in serum 5-MTHF as measured by the area under the curve over a period of 24 hours (AUC0-24h) after consumption of a single dose of 5-MTHF (400μg).

Participants will receive a single dose of each of the following products separated by a 7-day wash-out period:

* 5-MTHF glucosamine salt
* 5-MTHF calcium salt 1
* 5-MTHF calcium salt 2


Eligibility criteria: Inclusion Criteria:

* Body Mass Index (BMI) ≥18 and ≤25Kg/m²,
* For women: menopausal without hormone replacement therapy (HRT) or with HRT started from more than 3 months or non-menopausal with a negative blood pregnancy test and using 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,
* Good general and mental health within 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/her dated and signed informed consent form,
* Affiliated with a social security scheme,
* Agree to be registered on the subjects in biomedical research file.

After V1 biological analysis the subjects will be eligible to the study on the following criteria:

- Adequate folate status (serum folate between 10 and 45nmol/L, erythrocyte (RBC) folate between 405 and 952 nmol/L),

Exclusion Criteria:

* Suffering from a metabolic disorder,
* Suffering from a severe chronic disease found to be inconsistent with the conduct of the study by the investigator,
* Suffering from diseases that could potentially interfere with folate absorption or metabolism,
* With a known or suspected food allergy or intolerance or hypersensitivity to any of the study products' ingredient,
* With a low venous capital of blood samples according to the investigator's opinion,
* Pregnant or was pregnant less than 6 months prior to the study, or lactating women or intending to become pregnant within 3 months ahead,
* Under treatment or regular use of treatment or dietary supplement which could significantly affect folate status or other study parameter(s),
* Use of supplements containing folate (i.e. folic acid, 5-MTHF) the last 3 months,
* With significant change in lifestyle, food habits, physical activity or medications in the 3 months before the V1 visit or not agreeing to keep them unchanged throughout the study,
* With a current or planned in the next 3 months' specific diet (hyper or hypocaloric, vegan, vegetarian...) or stopped less than 3 months before the study,
* With a personal history of anorexia nervosa, bulimia or significant eating disorders according to the investigator,
* Consuming more than 2 standard drinks of alcoholic beverage daily for men and women or not agreeing to keep his alcohol consumption habits unchanged throughout the study.
* Smoking,
* Having a lifestyle deemed incompatible with the study according to the investigator including high level physical activity,
* 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.
* Who made a blood donation in the 3 months before the V0 visit or intending to make it within 3 months ahead.

After V1 biological analysis the subjects will be non-eligible to the study on the following criteria:

* Presence of anemia (hemoglobin\<12g/dL in women and 13g/dL in men),
* Vitamin B12 levels (serum cobalamin \<148pmol/L),
* Serum total homocysteine levels≥15µmol/L,
* Serum creatinine \>0,96mg/dL for women and \>1,21mg/dL for men,
* Control record (Glycaemia, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, GGT, ASAT, ALAT, Urea and CBC) with clinically significant abnormality according to the investigator.

Primary outcomes:
measure: Area under the curve (AUC) 0-24 hours of serum 5-MTHF concentrations
timeFrame: 0-24 hours
Secondary outcomes:
measure: Area under the curve (AUC) 0-24 hours of serum total folate concentrations
timeFrame: 0-24 hours
measure: Area under the curve (AUC) 0-8 hours of serum 5-MTHF and total folate concentrations
timeFrame: 0-8 hours
measure: Area under the curve (AUC) 0-infinity of serum 5-MTHF and total folate concentrations
timeFrame: 0-24 hours
measure: Peak plasma concentrations (Cmax) of serum 5-MTHF and total folate
timeFrame: 0-24 hours
measure: Half-life time of serum 5-MTHF and total folate
timeFrame: 0-24 hours
measure: Mean Residence Time (MRT) of serum 5-MTHF and total folate
timeFrame: 0-24 hours
measure: Area under the curve (AUC) 0-24 hours of serum 5-MTHF and total folate concentrations adjusted on sex
timeFrame: 0-24 hours
Other outcomes:
measure: Frequency of adverse events (AE)
timeFrame: 4 weeks (inclusion to last visit)
measure: Frenquency of Treatment-Emergent Adverse events (TEAE)
timeFrame: 4 weeks (inclusion to last visit)
measure: Frenquency of Serious treatment-emergent adverse events (STEAE)
timeFrame: 4 weeks (inclusion to last visit)
Locations:
city: Saint-Herblain
country: France
facility: Biofortis
Study officials:
affiliation: BioFortis
name: Isabelle METREAU, MD
role: PRINCIPAL_INVESTIGATOR
References: