Pharmacokinetic Study on Three Formulations of Curcumin With Different Carriers
试验速览
- 阶段
- 不适用
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Neither the participant nor the research nurse will know the administration order of the different treatments administered. All plasma samples collected during the research project will be anonymized. Also, it will not be possible to identify the participant by his name since a number will be assigned to him. The code key linking the participant's name to his number will be stored, with access restricted to those designated by the principal investigator. The data file is also protected by a password.
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •Allergy to fish or seafood.
- •Special diet like a vegetarian or vegan diet.
- •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.
结局指标
主要结局
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
时间窗: 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.
Plasma curcumin levels will be measured by ultra-performance liquid chromatography (UPLC), each sample being performed randomly blindly. After UPLC analyzes, area under the curve (AUC) 0-48 hours will be calculated, as the first parameter of the PK. Statistical analyzes will then be performed on this PK parameter.
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
时间窗: 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.
Plasma curcumin levels will be measured by ultra-performance liquid chromatography (UPLC), each sample being performed randomly blindly. After UPLC analyzes, time when the maximum concentration is reached will be calculated, as the fourth parameter of the PK. Statistical analyzes will then be performed on this PK parameter.
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
时间窗: 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.
Plasma curcumin levels will be measured by ultra-performance liquid chromatography (UPLC), each sample being performed randomly blindly. After UPLC analyzes, AUC 0-6 hours (absorption study) will be calculated, as the second parameter of the PK. Statistical analyzes will then be performed on this PK parameter.
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
时间窗: 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.
Plasma curcumin levels will be measured by ultra-performance liquid chromatography (UPLC), each sample being performed randomly blindly. After UPLC analyzes, maximum concentration will be calculated, as the third parameter of the PK. Statistical analyzes will then be performed on this PK parameter.
次要结局
未报告次要终点
研究者
Mélanie Plourde
PhD
Université de Sherbrooke