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临床试验/NCT04731987
NCT04731987已完成不适用

Orange Juice, Hesperidin and Their Role in Vascular Health Benefit: a Human Double Blind, Randomized, Controlled, Cross Over Study

University Hospital, Clermont-Ferrand2 个研究点 分布在 1 个国家目标入组 50 人开始时间: 2021年2月24日最近更新:
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适应症

试验速览

阶段
不适用
状态
已完成
发起方
入组人数
50
试验地点
2
主要终点
Brachial artery Flow Mediated Dilation (FMD)
研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Although epidemiological studies have associated the consumption of sugary beverages with adverse health effects, experimental studies have demonstrated that the metabolic response of the human body to fruit juice as compared to artificial beverages is substantially different. Fruit juices do not just provide sugars and related calories, but they are rich sources of bioactive compounds especially of flavonoids. Flavanones constitute a class of flavonoids that are specifically and abundantly found in citrus fruits, with hesperidin being the major compound in orange. From prospective cohort studies, higher intakes of flavanones are associated with a lower incidence of mortality by cardiovascular disease (CVD). This relation is supported by results from a number of animal studies demonstrating a slowdown in atherosclerosis development and vascular protective effects in dietary interventions with flavanones. Randomized, controlled clinical trials to corroborate the suggested vasculo-protective effects of orange juice presumably mediated by the flavanones are scarce and available data do not allow to draw firm conclusions about their efficacy. To fill this gap, the "HESPER-HEALTH study" conducted in humans will assess the vascular protective effects of 100% orange juice consumption and evaluate the contribution of hesperidin in these effects.

详细描述

This human dietary intervention study is a double blind, randomized, placebo controlled, cross over trial with 3 arms, carried out on subjects with predisposition to cardiovascular diseases (CVD) based on age and overweight. This study aims to demonstrate the vascular protective effects (with Flow Mediated Dilatation (FMD) as main criteria) of the consumption of a flavanone rich orange juice or of orange flavanones by comparison with a control sugary drink alone.

The 42 recruited participants will receive the 3 drinks in a random order. For each subject, the study is divided into 3 identical experimental periods of 45 days (period 1,2,3): including 3 days prior to the beginning of the product intake, during which specific dietary guidelines, samplings and measures will be asked to be performed at home followed by a 6 weeks period of consumption of each of the 3 beverages). A period of 4 to 6 weeks of wash-out is planned between each experimental period.

To summarize: Visit 1 (D-14) = inclusion, Visit 2 (D1: baseline) to 3 (D42) = period 1, Visit 3 (D42) to 4 (D70) = wash out 1, Visit 4 (D70) to 5 (D111) = period 2, Visit 5 (D111) to 6 (D139) = wash out 2, Visit 6 (D139) to 7 (D180) = period 3. The wash-out periods (minimum duration: 4 weeks) may be extended until 6 weeks for the convenience of participants.

The protocol includes a total of 7 visits to PIC/CIC Inserm 1405 of the Clermont-Fd University Hospital.

The total duration of the study will be between 28 and 34 weeks

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Crossover
主要目的
Basic Science
盲法
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

盲法说明

drinks kits will be labelled and packaged according to the pre-established randomization plane by the pharmacy department of University Hospital of Clermont-Ferrand, France. Kits will be distributed in a blind fashion for each cross over period on the basis of the randomization schedule.

入排标准

年龄范围
40 Years 至 65 Years（Adult, Older Adult）
性别
All
接受健康志愿者
是

入选标准

  • •Man or post-menopausal woman ;
  • •40-65 years old (inclusive) ;
  • •Body Mass Index (BMI)≤ 30 ;
  • •Waist circumference ≥80 cm for women, and ≥94 cm for men ;
  • •Weight > 46 kg
  • •Normal biological balance sheet or considered normal by the investigator
  • •No aversion or intolerance to citrus foods ;
  • •Accept to limit their total intake of flavonoid rich beverages (tea, coffee, cocoa, wine, fruit juice) to 250 mL/day ;
  • •Ability to give informed consent to participate in research ;
  • •Willingness to accept randomization and undergo the testing and intervention procedures and deliver stool, blood and urine samples for testing ;
  • •Affiliation to Social Security.

排除标准

  • •Treated pre-diabetic or diabetic ;
  • •Treated for hypertension ;
  • •Use of statins or other medications for lowering cholesterol ;
  • •Treated with antibiotics, antifungals, probiotics or prebiotics in the 3 months before the enrolment ;
  • •Menopausal hormone replacement therapy ;
  • •Diagnosed gastrointestinal illness in the judgement of the investigator ;
  • •Any serious medical condition that precludes safe participation in the study, such as coronary artery disease, peripheral vascular disease, stroke, congestive heart failure, chronic obstructive pulmonary disease, insulin-dependent diabetes, psychiatric disease, renal disease, liver disease, active cancer and anemia ;
  • •History of eating disorders such as bulimia nervosa, anorexia nervosa and severe binge eating disorder in the last 5 years ;
  • •Digestive disorders with diarrhea during the 3 months preceding the beginning of the study ;
  • •Self-declared vegetarian, vegetalian, vegan ;
  • •History of substance abuse or alcohol abuse ;
  • •Involvement in a weight loss intervention program (including anti-obesity medication) within the past 3 months or who have had bariatric surgery ;
  • •Current smokers (within the last 30 days) ;
  • •Use of dietary supplements (vitamins, antioxidants) currently or in the past one month ;
  • •Strenuous exercise greater than 6 hours per week ;
  • •Anyone who in the opinion of the investigator is unlikely to be able to comply with the protocol ;
  • •Subjects involved in another clinical trial or being in the exclusion period of another study or having received a total compensation greater than 4,500 euros over the 12 months preceding the start of the trial ;
  • •Subject benefiting from a legal protection measure (curatorship, guardianship, safeguard of justice) ;
  • •Refusal to participate.

结局指标

主要结局

Brachial artery Flow Mediated Dilation (FMD)

时间窗: Day 180

The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state

次要结局

  • Plasma Interleukin 6 (IL-6) dosage(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma glucose dosage on fasted state(Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • -Plasma Triacylglycerol (TAG) dosage on fasted state(Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma uric acid on 6h post prandial state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Height measure(Day -14)
  • RNA profiling on fasted state(Day 42, Day 111, Day 180)
  • RNA profiling on 6h post prandial state(Day 42, Day 111, Day 180)
  • Gut microbiota profiling(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma carotenoids dosage(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma total cholesterol dosage(Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma High Density Lipoprotein cholesterol (HDL-chol) dosage(Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma High Density Lipoprotein cholesterol (LDL-chol) calculation(Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Weight measure(Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Waist circumference measure(Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Lean mass ratio determination(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Body Mass Index (BMI) calculation(Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Fat mass ratio determination(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Water mass ratio determination(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma vitamine C dosage(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Biobank for food metabolome(Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Treatment compliance(Day 42, Day 111, Day 180)
  • Polyphenol intake(Day 1, Day 42, Day 111, Day 180)
  • Carbohydrate intake(Day 1, Day 42, Day 111, Day 180)
  • Diet division of protein/lipid/carbohydrate intakes(Day 1, Day 42, Day 111, Day 180)
  • Diet stability(Day 180)
  • Calorie intake(Day 1, Day 42, Day 111, Day 180)
  • Protein intake(Day 1, Day 42, Day 111, Day 180)
  • Low-polyphenol diet compliance(Day 1, Day 42, Day 111, Day 180)
  • Lipid intake(Day 1, Day 42, Day 111, Day 180)
  • Basal Heart Rate(Day -14)
  • D-3 visit diastolic BP(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • D-3 visit Heart Rate(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • FMD post prandial endothelial response 6h after a challenge meal(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Rest flow by Flowmetry Laser Doppler (FLD) in fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Hyperaemia area / occlusion area ratio by FLD in fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • D-3 visit systolic Blood Pressure (BP)(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • FMD post prandial endothelial response 3h after a challenge meal(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Arterial compliance assessment(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Sex(Day -14)
  • Age(Day 34)
  • Occlusion area by FLD in fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Hyperaemia area by FLD in fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Occlusion area by FLD 3h after a challenge meal(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Hyperaemia area by FLD 3h after a challenge meal(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Hesperetin catabolites concentration in plasma on fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Basal Systolic Blood Pressure(Day -14)
  • Hesperetin concentration in 24h urine(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Hyperaemia half time by FLD in fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Rest flow by FLD 3h after a challenge meal(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Hyperaemia area / occlusion area ratio by FLD 6h after a challenge meal(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Hyperaemia half time by FLD 6h after a challenge meal(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Hesperetin concentration in plasma on fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Naringenin catabolites concentration in 24h urine(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Naringenin concentration in plasma on fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Maximal flow by FLD in fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Hyperaemia half time by FLD 3h after a challenge meal(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Hyperaemia area / occlusion area ratio by FLD 3h after a challenge meal(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Maximal flow by FLD 3h after a challenge meal(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Rest flow by FLD 6h after a challenge meal(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Hyperaemia area by FLD 6h after a challenge meal(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Naringenin catabolites concentration in plasma on 3h post prandial test(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Naringenin concentration in plasma on 6h post prandial test(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Flavanone catabolites concentration in plasma on 6h post prandial test(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma nitrites dosage(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma Vascular-CAM (VCAM) dosage on fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Occlusion area by FLD 6h after a challenge meal(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Maximal flow by FLD 6h after a challenge meal(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Hesperetin concentration in plasma on 3h post prandial test(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Hesperetin catabolites concentration in plasma on 3h post prandial test(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Hesperetin concentration in plasma on 6h post prandial test(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Hesperetin catabolites concentration in plasma on 6h post prandial test(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Naringenin concentration in 24h urine(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Naringenin concentration in plasma on 3h post prandial test(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Naringenin catabolites concentration in plasma on fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Flavanone catabolites concentration in 24h urine(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Naringenin catabolites concentration in plasma on 6h post prandial test(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Flavanone concentration in 24h urine(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Flavanone catabolites concentration in plasma on fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Flavanone concentration in plasma on 3h post prandial test(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma Inter-Cellular Adhesion Molecules (ICAM) dosage on fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma ICAM dosage on 6h post prandial state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Flavanone catabolites concentration in plasma on 3h post prandial test(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma Extracellular Vesicles analyses (EVs) on fasted state(Day 42, Day 111, Day 180)
  • Flavanone concentration in plasma on fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma nitroso-thiols dosage(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Flavanone concentration in plasma on 6h post prandial test(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma e-selectin dosage on fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma e-selectin dosage on 6h post prandial state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma VCAM dosage on 6h post prandial state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • EVs analyses on 3h post prandial state(Day 42, Day 111, Day 180)
  • Plasma oxylipins identification on fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma oxylipin concentration on fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma oxylipin concentration on 6h post prandial state(Day 42, Day 111, Day 180)
  • Plasma Tumor Necrosis Factor α (TNFα) dosage(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma high-sensitivity C-reactive protein (hs-CRP) dosage(Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma glucose dosage on 3h post prandial state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma glucose dosage on 6h post prandial state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma TAG dosage on 3h post prandial state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma TAG dosage on 6h post prandial state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma uric acid dosage on fasted state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma uric acid on 3h post prandial state(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma Total Fatty Acids (FA) dosage(Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Serum Insulin dosage(Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180)
  • Plasma oxylipins identification on 6h post prandial state(Day 42, Day 111, Day 180)

研究者

发起方
University Hospital, Clermont-Ferrand
申办方类型
Other
责任方
Sponsor

研究点 (2)

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