Clinical trial NCT04382014: Pharmacokinetic Study on Three Formulations of Curcumin With Different Carriers
Official title: Pharmacokinetic Study on Three Formulations of Curcumin With Different Carriers
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Healthy
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
First posted: 2020-05-11
Enrollment: 30
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: Double-blind controlled-randomized pharmacokinetic (PK) study with crossover design (15 men and 15 women), with a minimum of 6 days between treatments
Primary purpose: TREATMENT

Brief summary: Curcumin is a molecule soluble in fat. It has multiple health benefits. Indeed, it has anti-inflammatory and anti-oxidant properties. Curcumin could play a role in preventing diseases such as cancer, inflammatory, cardiovascular and neurodegenerative diseases. Omega-3 fatty acids are also important for good health, as they have positive effects on the cardiovascular and neurological systems. However, curcumin is poorly absorbed by the body when provided in supplements. In order to improve curcumin's absorption, a natural health product that combines curcumin and omega-3 fatty acids has been developped. The goal of this project is therefore to determine the absorption of curcumin when administered in combination with omega-3 fatty acids esterified in monoacylglycerol (MAG). This combination will be compared with a curcumin extract alone or in rice oil. A pharmacokinetic study will be carried out for each of the formulations. Pharmacokinetics (PK) is defined as monitoring the blood concentrations of curcumin over a 24-hour period after taking one of the three different supplements.

Detailed description: 15 men and 15 women in good health conditions will be recruited for this project. The study has a randomized double-blinded crossover design with three treatments that include an equal dosage of curcumin as follows :

* 400 mg of curcumin extract,
* 400 mg of curcumin in rice oil,
* 400 mg of curcumin extract + 1.5 g omega-3 in MAG form.

For each of the above listed products, a natural product number (NPN) was requested to Health Canada and these number are currently pending.

Each participant will consume each of the three treatments in a random order with a minimum of 7 days washout phase between both treatments. Blood samples will be collected at time 0, 1, 2, 3, 4, 5, 6, 8, 10, and 24h (10 blood samples per participant per treatment) after taking the single dose intake. A questionnaire will allow documenting side effects throughout the study period. The analyses will be performed by ultra-high-performance liquid chromatography couples to a quadrupole mass spectrometer (UPLC/MS/MS). Samples will be analyzed in a blinded manner such that the student and research assistant will be blinded from the type of treatment and the time point they are analyzing. After performing all the analyses, sample identification will be decoded and pharmacokinetic data of the curcuminoids in each of the treatments will be plotted on a plasma concentration vs time curve. The parameters below will be calculated:

* Area under the curve (AUC) 0-24h (bioavailability);
* Area under the curve (AUC) 0-6h (absorption);
* Maximum concentration (Cmax);
* Time to reach the maximum concentration (Tmax);
* Half-life (if available).

Eligibility criteria: Inclusion Criteria:

* Men or women between 18 and 50 years old (inclusive).
* Body mass index between 18,5 and 34,9 at the selection visit (inclusive).
* Normal to moderately high lipidemia (total cholesterol ≤ 240 mg / dl; LDL ≤ 160 mg / dl; Triglyceride ≤ 199 mg / dl).
* Women of child bearing potential must accept to use an effective contraceptive method for the duration of the study.

Exclusion Criteria:

* Allergy to fish or seafood.
* Special diet like a vegetarian or vegan diet.
* Tobacco.
* History of current or past alcohol and / or drug abuse.
* Current or past performance athlete.
* Malnutrition (assessed by albumin, hemoglobin and blood lipid levels).
* People consuming omega 3 fatty acid or curcumin supplements for more than 6 months.
* Medication affecting fat absorption (ie, Orlistat, Alli, etc.).
* Medication which interferes with the metabolization of the medication (ie, anticoagulants like coumadin or warfarin, aspirin is not an exclusion criterion (Watson et al, 2009))
* Medication which affects lipid metabolism (ie, all types of drugs to lower cholesterol or triglycerides).
* Medication which curcumin interacts with : angiotensin II blockers (losartan, valsartan), β-blockers (talinolol, celiprolol), calcium channels blockers (nifedipine), 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG CoA) reductase inhibitors (rosuvastatin), antineoplastic agents (docetaxel, etoposide, tamoxifen, everolimus, sirolimus), antibiotics (norfloxacin), antidepressant (midazolam), sulfonamides (sulfasalazine), antidiabetics (gliclazide).
* Pregnant women or nursing women.
* Menopause or pre-menopause with amenorrhea \> 6 months.
* Systemic disease: vasculitis, Lupus Erythrocyte Disseminated (SLE), sarcoidosis, cancer (except if in remission for more than 10 years and without cerebral involvement), uncompensated hypothyroidism, vitamin B12 deficiency not supplemented and / or complicated, diabetes, severe renal insufficiency.
* Abnormal liver, kidney or thyroid function; these conditions will not exclude a patient if he / she has been stabilized on treatment for at least 3 months and there has been no recent change in his / her medication.
* Cardiac event or recent major surgery (\<6 months).
* History of thrombosis or haemorrhagic diathesis.
* Malabsorption disease such as pancreatitis, Crohn's disease or has had bariatric surgery.
* Neurodegenerative disease (Parkinson disease).
* Genetic disorder (Down syndrome).
* Known psychiatric history: schizophrenia, psychotic disorders, major affective disorder (bipolar disorder and major depression \<5 years), panic disorder, Compulsive Obsessive Compulsive Disorder (OCD).
* Neurological disorder (Epilepsy, cerebral trauma with loss of consciousness, subarachnoid hemorrhage).
* Person who has donated blood or had significant blood loss in the 30 days prior to the start of the study.
* Not available to perform the 3 treatments.

Primary outcomes:
measure: Determine the bioavailability of curcumin in combination with fish oil, rice oil or alone: Calculating the area under the curve (AUC) 0-48h as the first parameter of the PK
timeFrame: Treatments are randomly assigned on days 1, 8 and 15 of the clinical study. UPLC analyzes will be measured on plasma from blood samples collected at time 0, 1, 2, 3, 4, 5, 6, 8, 10 and 24 hours post-treatment.
measure: Determine the bioavailability of curcumin in combination with fish oil, rice oil or alone: Calculating the AUC 0-6h (absorption study) as the second parameter of the PK
timeFrame: Treatments are randomly assigned on days 1, 8 and 15 of the clinical study. UPLC analyzes will be measured on plasma from blood samples collected at time 0, 1, 2, 3, 4, 5, 6, 8, 10 and 24 hours post-treatment.
measure: Determine the bioavailability of curcumin in combination with fish oil, rice oil or alone: Calculating the maximum concentration as the third parameter of the PK
timeFrame: Treatments are randomly assigned on days 1, 8 and 15 of the clinical study. UPLC analyzes will be measured on plasma from blood samples collected at time 0, 1, 2, 3, 4, 5, 6, 8, 10 and 24 hours post-treatment.
measure: Determine the bioavailability of curcumin in combination with fish oil, rice oil or alone: Calculating the time when the maximum concentration is reached, as the fourth parameter of the PK
timeFrame: Treatments are randomly assigned on days 1, 8 and 15 of the clinical study. UPLC analyzes will be measured on plasma from blood samples collected at time 0, 1, 2, 3, 4, 5, 6, 8, 10 and 24 hours post-treatment.
Secondary outcomes:
Other outcomes:
Locations:
city: Sherbrooke
country: Canada
facility: Centre de Recherche sur le Vieillissement
state: Quebec
Study officials:
affiliation: Université de Sherbrooke
name: Melanie Plourde, PhD
role: PRINCIPAL_INVESTIGATOR
References: