AzTrials
AzTrials

Metabolic SyndromeHESPER-HEALTHNCT04731987

Orange Juice, Hesperidin and Their Role in Vascular Health Benefit

A study testing Beverage consumption in people with Metabolic Syndrome and Vascular Compliance, run by University Hospital, Clermont-Ferrand at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 40 to 65 yearsHealthy volunteers can take part
What is being tested?
Beverage consumption
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
50 participants
Where
1 siteFrance
Study dates
24 Feb 2021to 20 Jun 2023
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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 ;
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  • 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.

Trial locations and contacts

1 site in 1 country.

France1 site

  • University Hospital, Clermont Ferrand

    Clermont-Ferrand, AURA, 63000

Other trials in France

About this study

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

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.

Read the detailed description

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

Being tested
Beverage consumption
Keywords
Cardiovascular disease prevention, Endothelial dysfunction, Orange juice, Flavanone, Hesperidin, Nutrition Assessment, Nutritional Physiological Phenomena
Medical subject headings
Metabolic Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Beverage consumptionBehavioural

    Volunteers will consume, in random order, daily 330 ml of 1 experimental beverage per period (Orange Juice, Control Beverage, Control Beverage supplemented with hesperidin) for 6 weeks in each period.

    At the beginning and the end of each period, exploration will be conducted at fasted state and at post-prandial state after the administration of a high-fat high-sugar meal.

Study groups in NCT04731987
Study groupRoleWhat they receive
Orange juice (A)Experimental42 subjects between 40 and 65 years old with predisposition to cardiovascular disease will consume daily 330 ml of orange juice naturally rich in hesperidin (drink A) during 6 weeks
Receives: Behavioral: Beverage consumption
Control beverage (B)Placebo comparator42 subjects between 40 and 65 years old with predisposition to cardiovascular disease will consume daily 330 ml of control beverage (drink B)- a soft drink with sugar concentration identical to drink A - during 6 weeks
Receives: Behavioral: Beverage consumption
Control beverage supplemented with hesperidin formulation (B+HESP)Experimental42 subjects between 40 and 65 years old with predisposition to cardiovascular disease will consume daily 330 ml of control beverage (identical to drink B but supplemented with hesperidin to reach level of drink A) during 6 weeks
Receives: Behavioral: Beverage consumption

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Brachial artery Flow Mediated Dilation (FMD)

    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

    Measured: Day 1

  2. Brachial artery Flow Mediated Dilation (FMD)

    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

    Measured: Day 42

  3. Brachial artery Flow Mediated Dilation (FMD)

    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

    Measured: Day 70

  4. Brachial artery Flow Mediated Dilation (FMD)

    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

    Measured: Day 111

  5. Brachial artery Flow Mediated Dilation (FMD)

    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

    Measured: Day 139

  6. Brachial artery Flow Mediated Dilation (FMD)

    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

    Measured: Day 180

Secondary outcomes (104)

  1. Sex

    Participant sex (man/women) will be requested.

    Measured: Day -14

  2. Age

    Participant age (years) will be requested.

    Measured: Day 34

  3. Basal Systolic Blood Pressure

    Blood pressure measure (mm Hg) with monitor.

    Measured: Day -14

  4. Basal Heart Rate

    Heart rate measure (beat/min) with monitor.

    Measured: Day -14

  5. D-3 visit systolic Blood Pressure (BP)

    Self-monitored blood pressure (mmHg) at home with tensiometer, at home the morning, 3 days before the visit, in fasted state.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  6. D-3 visit diastolic BP

    Self-monitored blood pressure (mmHg) at home with tensiometer, at home the morning, 3 days before the visit, in fasted state.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  7. D-3 visit Heart Rate

    Self-monitored heart rate (beat/min) at home with tensiometer,at home the morning, 3 days before the visit, in fasted state.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  8. FMD post prandial endothelial response 3h after a challenge meal

    Assessment of the postprandial endothelial response to a challenge meal (900kcal, fresh cream, sucrose and milk proteins) by measuring FMD (percent) using ultrasound technique, 3h after intake of the full daily dose of study products concomitantly with challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  9. FMD post prandial endothelial response 6h after a challenge meal

    Assessment of the postprandial endothelial response to a challenge meal by measuring FMD (percent) using ultrasound technique, 6h after intake of the full daily dose of study products concomitantly with challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  10. Arterial compliance assessment

    Noninvasive measure with Sphygmocor (AtCor Medical Pty. Ltd) of pulse transit time between carotid artery and femoral artery. The carotid-femoral Pulse Wave Velocity (PWV) (m/sec) is an established index of arterial stiffness,in fasted state.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  11. Rest flow by Flowmetry Laser Doppler (FLD) in fasted state

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the rest flow using laser-Doppler system at the level of the skin of the hand, in fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  12. Occlusion area by FLD in fasted state

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the occlusion area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement) in fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  13. Hyperaemia area by FLD in fasted state

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement) in fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  14. Hyperaemia area / occlusion area ratio by FLD in fasted state

    Vascular endothelial function in the micro-vascular compartment will be assessed using the ratio hyperaemia area / occlusion area determined by FLD.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  15. Maximal flow by FLD in fasted state

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the maximal flow using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), in fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  16. Hyperaemia half time by FLD in fasted state

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia half time using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), in fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  17. Rest flow by FLD 3h after a challenge meal

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the rest flow using laser-Doppler system at the level of the skin of the hand,3h after intake of the full daily dose of study products concomitantly with challenge meal

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  18. Occlusion area by FLD 3h after a challenge meal

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the occlusion area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 3h after intake of the full daily dose of study products concomitantly with challenge meal

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  19. Hyperaemia area by FLD 3h after a challenge meal

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 3h after intake of the full daily dose of study products concomitantly with challenge meal

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  20. Hyperaemia area / occlusion area ratio by FLD 3h after a challenge meal

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the ratio hyperaemia area/ occlusion area determined by FLD, 3h after intake of the full daily dose of study products concomitantly with challenge meal

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  21. Maximal flow by FLD 3h after a challenge meal

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the maximal flow using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 3h after intake of the full daily dose of study products concomitantly with challenge meal

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  22. Hyperaemia half time by FLD 3h after a challenge meal

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia half time using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 3h after intake of the full daily dose of study products concomitantly with challenge meal

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  23. Rest flow by FLD 6h after a challenge meal

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the rest flow using laser-Doppler system at the level of the skin of the hand, 6h after intake of the full daily dose of study products concomitantly with challenge meal

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  24. Occlusion area by FLD 6h after a challenge meal

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the occlusion area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 6h after intake of the full daily dose of study products concomitantly with challenge meal

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  25. Hyperaemia area by FLD 6h after a challenge meal

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 6h after intake of the full daily dose of study products concomitantly with challenge meal

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  26. Hyperaemia area / occlusion area ratio by FLD 6h after a challenge meal

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the ratio hyperaemia area / occlusion area ratio determined by FLD, 6h after intake of the full daily dose of study products concomitantly with challenge meal

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  27. Maximal flow by FLD 6h after a challenge meal

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the maximal flow using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 6h after intake of the full daily dose of study products concomitantly with challenge meal

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  28. Hyperaemia half time by FLD 6h after a challenge meal

    Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia half time using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 6h after intake of the full daily dose of study products concomitantly with challenge meal

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  29. Hesperetin concentration in 24h urine

    Concentration of hesperetin in urine (nM) will be measured.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  30. Hesperetin concentration in plasma on fasted state

    Concentration of hesperetin in plasma (nM) will be measured.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  31. Hesperetin catabolites concentration in plasma on fasted state

    Concentration of hesperetin microbial catabolites in plasma (nM) will be measured, on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  32. Hesperetin concentration in plasma on 3h post prandial test

    Concentration of hesperetin in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  33. Hesperetin catabolites concentration in plasma on 3h post prandial test

    Concentration of hesperetin microbial catabolites in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  34. Hesperetin concentration in plasma on 6h post prandial test

    Concentration of hesperetin in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  35. Hesperetin catabolites concentration in plasma on 6h post prandial test

    Concentration of hesperetin microbial catabolites in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  36. Naringenin concentration in 24h urine

    Concentration of naringenin in urine (nM) will be measured.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  37. Naringenin catabolites concentration in 24h urine

    Concentration of naringenin microbial catabolites in urine (nM) will be measured.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  38. Naringenin concentration in plasma on fasted state

    Concentration of naringenin in plasma (nM) will be measured, on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  39. Naringenin catabolites concentration in plasma on fasted state

    Concentration of naringenin microbial catabolites in plasma (nM) will be measured, on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  40. Naringenin concentration in plasma on 3h post prandial test

    Concentration of naringenin in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  41. Naringenin catabolites concentration in plasma on 3h post prandial test

    Concentration of naringenin microbial catabolites in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  42. Naringenin concentration in plasma on 6h post prandial test

    Concentration of naringenin in plasma (mM) will be measure, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  43. Naringenin catabolites concentration in plasma on 6h post prandial test

    Concentration of naringenin microbial catabolites in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  44. Flavanone concentration in 24h urine

    Concentration of flavanone in urine (nM) will be measured.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  45. Flavanone catabolites concentration in 24h urine

    Concentration of flavanone microbial catabolites in urine (nM) will be measured.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  46. Flavanone concentration in plasma on fasted state

    Concentration of flavanone in plasma (nM) will be measured, on fasted state.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  47. Flavanone catabolites concentration in plasma on fasted state

    Concentration of flavanone microbial catabolites in plasma (nM) will be measured, on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  48. Flavanone concentration in plasma on 3h post prandial test

    Concentration of flavanone in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  49. Flavanone catabolites concentration in plasma on 3h post prandial test

    Concentration of flavanone microbial catabolites in plasma (mM) will be measured,in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  50. Flavanone concentration in plasma on 6h post prandial test

    Concentration of flavanone in urine (nM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  51. Flavanone catabolites concentration in plasma on 6h post prandial test

    Concentration of flavanone microbial catabolites in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  52. Plasma nitrites dosage

    Determination of nitrite plasma concentration (nM) (a biomarker of endothelial activation), on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  53. Plasma nitroso-thiols dosage

    Determination of nitroso-thiols plasma concentration (nM) (a biomarker of endothelial activation), on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  54. Plasma Inter-Cellular Adhesion Molecules (ICAM) dosage on fasted state

    Determination of ICAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  55. Plasma ICAM dosage on 6h post prandial state

    Determination of ICAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on 6h post prandial state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  56. Plasma Vascular-CAM (VCAM) dosage on fasted state

    Determination of VCAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  57. Plasma VCAM dosage on 6h post prandial state

    Determination of VCAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on 6h post prandial state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  58. Plasma e-selectin dosage on fasted state

    Determination of e-selectin plasma concentration (ng/ml) (a biomarker of endothelial activation), on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  59. Plasma e-selectin dosage on 6h post prandial state

    Determination of e-selectin plasma concentration (ng/ml) (a biomarker of endothelial activation), on 6h post prandial state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  60. Plasma Extracellular Vesicles analyses (EVs) on fasted state

    EVs (a biomarker of endothelial activation) will be isolated from platelet-poor plasma samples and analyzed, on fasted state

    Measured: Day 42, Day 111, Day 180

  61. EVs analyses on 3h post prandial state

    EVs (a biomarker of endothelial activation) will be isolated from platelet-poor plasma samples and analyzed, on post prandial state 3h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 42, Day 111, Day 180

  62. Plasma oxylipins identification on fasted state

    Determination of oxylipins present in plasma (a biomarker of inflammation and oxidative stress) using a method of profiling, on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  63. Plasma oxylipin concentration on fasted state

    Determination of oxylipin plasma concentration (a biomarker of inflammation and oxidative stress), on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  64. Plasma oxylipins identification on 6h post prandial state

    Determination of oxylipins present in plasma (a biomarker of inflammation and oxidative stress) using a method of profiling, on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 42, Day 111, Day 180

  65. Plasma oxylipin concentration on 6h post prandial state

    Determination of oxylipin plasma concentration (a biomarker of inflammation and oxidative stress), on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 42, Day 111, Day 180

  66. Plasma Interleukin 6 (IL-6) dosage

    Determination of IL-6 plasma concentration (pg/ml) (a biomarker of inflammation and oxidative stress), on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  67. Plasma Tumor Necrosis Factor α (TNFα) dosage

    Determination of TNFα plasma concentration (pg/ml) (a biomarker of inflammation and oxidative stress), on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  68. Plasma high-sensitivity C-reactive protein (hs-CRP) dosage

    Determination of hs-CRP plasma concentration (mg/L) (a biomarker of inflammation and oxidative stress), on fasted state

    Measured: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  69. Plasma glucose dosage on fasted state

    Determination of glucose plasma concentration (mM) (a metabolic parameter), on fasted state

    Measured: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  70. Plasma glucose dosage on 3h post prandial state

    Determination of glucose plasma concentration (mM) (a metabolic parameter), on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  71. Plasma glucose dosage on 6h post prandial state

    Determination of glucose plasma concentration (mM) (a metabolic parameter), on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  72. -Plasma Triacylglycerol (TAG) dosage on fasted state

    Determination of TAG plasma concentration (g/L) (a metabolic parameter), on fasted state

    Measured: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  73. Plasma TAG dosage on 3h post prandial state

    Determination of TAG plasma concentration (g/L) (a metabolic parameter), on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal, on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  74. Plasma TAG dosage on 6h post prandial state

    Determination of TAG plasma concentration (g/L) (a metabolic parameter), on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  75. Plasma uric acid dosage on fasted state

    Determination of uric acid plasma concentration (mM) (a metabolic parameter) method, on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  76. Plasma uric acid on 3h post prandial state

    Determination of uric acid plasma concentration (mM) (metabolic parameter), on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  77. Plasma uric acid on 6h post prandial state

    Determination of uric acid plasma concentration (mM) (metabolic parameter) will be determined, on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  78. Plasma total cholesterol dosage

    Determination of total cholesterol plasma concentration (mM) (a metabolic parameter), on fasted state

    Measured: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  79. Plasma High Density Lipoprotein cholesterol (HDL-chol) dosage

    Determination of HDL-chol plasma concentration (mM) (a metabolic parameter), on fasted state

    Measured: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  80. Plasma High Density Lipoprotein cholesterol (LDL-chol) calculation

    Determination of LDL-chol plasma concentration (mM) (metabolic parameter), on fasted state

    Measured: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  81. Plasma Total Fatty Acids (FA) dosage

    Determination of total FA plasma concentration (mM) (a metabolic parameter), on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  82. Serum Insulin dosage

    Determination of insulin serum concentration (mU/L or pM) (a metabolic parameter), on fasted state

    Measured: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  83. Weight measure

    the body weight (kg) will be recorded with a bathroom scale, on fasted state

    Measured: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  84. Height measure

    the body height (cm) will be measured with a stadiometer.

    Measured: Day -14

  85. Body Mass Index (BMI) calculation

    the BMI (kg/m²) will be calculated, on fasted state

    Measured: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  86. Waist circumference measure

    the waist circumference (cm) will be recorded with a measuring tape, on fasted state

    Measured: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  87. Fat mass ratio determination

    The percentage of fat mass (percent) (body composition) will be determined on each participant using a multi-frequency bioelectrical Impedance Analyzer, on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  88. Lean mass ratio determination

    The percentage of lean mass (percent) (body composition) will be determined on each participant using a multi-frequency bioelectrical Impedance Analyzer, on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  89. Water mass ratio determination

    The percentage of water (percent) (body composition) will be determined using a multi-frequency bioelectrical Impedance Analyzer, on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  90. RNA profiling on fasted state

    Nutrigenomic analysis will be performed from total Ribo Nucleic Acid (RNA) isolated blood collected in PAXgene Blood RNA Tube. The isolated RNA will be used to perform microarray analyses that allow identification of expression of all genes of the genome, on fasted state

    Measured: Day 42, Day 111, Day 180

  91. RNA profiling on 6h post prandial state

    Analysis will be performed from total RNA isolated blood collected in PAXgene Blood RNA Tube. The isolated RNA will be used to perform microarray analyses that allow identification of expression of all genes of the genome, on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.

    Measured: Day 42, Day 111, Day 180

  92. Gut microbiota profiling

    Identification of the microbiota composition of feces samples (collected by subjects) by performing a genetic sequencing analysis of bacterial DNA.

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  93. Plasma carotenoids dosage

    Carotenoids will be quantitated from plasma (nM), on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  94. Plasma vitamine C dosage

    Vitamin C status will be quantified in deproteinized plasma (mg/L), on fasted state

    Measured: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

  95. Treatment compliance

    Treatment compliance (percent) will be determined using counting of empty orange drinks brought back by volunteers after the consumption periods

    Measured: Day 42, Day 111, Day 180

  96. Polyphenol intake

    Polyphenol intake (ml/day) in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.

    Measured: Day 1, Day 42, Day 111, Day 180

  97. Low-polyphenol diet compliance

    Respect (y/n) of a low-polyphenol diet in basal (between Visit 1 - Visit 2) and during treatment consumption periods (between Visit 2 - Visit 3, Visit 4 - Visit 5, Visit 6 - Visit 7) will be determined by a dietician using 3 days food reports completed by volunteers.

    Measured: Day 1, Day 42, Day 111, Day 180

  98. Calorie intake

    Calorie (kcal/day) intake in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.

    Measured: Day 1, Day 42, Day 111, Day 180

  99. Protein intake

    Protein (g/day) intake in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.

    Measured: Day 1, Day 42, Day 111, Day 180

  100. Lipid intake

    Lipid intake (g/day) in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.

    Measured: Day 1, Day 42, Day 111, Day 180

  101. Carbohydrate intake

    Carbohydrate intake (g/day) in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.

    Measured: Day 1, Day 42, Day 111, Day 180

  102. Diet division of protein/lipid/carbohydrate intakes

    The overall distribution of the protein/lipid/carbohydrate food intakes (%) will be determined by a dietician using food report completed by volunteers.

    Measured: Day 1, Day 42, Day 111, Day 180

  103. Diet stability

    Diet stability (y/n) in terms of polyphenols, calories, proteins, carbohydrates and lipids intakes during the whole study will be determined by a dietician using the 4 food reports completed by volunteers.

    Measured: Day 180

  104. Biobank for food metabolome

    Urine samples will be stored for further assessment of food metabolome to potentially identify new bioactive compounds present in the juice that could contribute to the biological response after orange juice/HESP intake.

    Measured: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Feb 2021
  2. Study start24 Feb 2021
  3. Primary completion20 Jun 2023
  4. Study completion20 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04731987
Sponsor's protocol ID
RBHP 2020 PICKERING 2
Acronym
HESPER-HEALTH
Status last verified
Jul 2024
First submitted
22 Jan 2021
Last updated
6 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Gilcher C, Milenkovic D, Taillandier M, Ruskovska T, Steingass CB, Macian N, Verny MA, Evrard R, Pereira B, Gladine C, Schweiggert R, Pickering G, Morand C. Orange juice and hesperidin increase flavanone exposure without detectable short-term vascular benefits: a randomized crossover trial. Food Funct. 2026 Sep 1;17(17):7651-7669. doi: 10.1039/d6fo02778d.

    PubMed 42605853

  • Verny MA, Milenkovic D, Macian N, Pereira B, Evrard R, Gilcher C, Steingass CB, Mosoni P, Gladine C, Monfoulet LE, Schweiggert R, Pickering G, Morand C. Evaluating the role of orange juice, HESPERidin in vascular HEALTH benefits (HESPER-HEALTH study): protocol for a randomised controlled trial. BMJ Open. 2021 Nov 30;11(11):e053321. doi: 10.1136/bmjopen-2021-053321.

    PubMed 34848522

Questions about this trial

What is this clinical trial studying?

A study testing Beverage consumption in people with Metabolic Syndrome and Vascular Compliance, run by University Hospital, Clermont-Ferrand at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Brachial artery Flow Mediated Dilation (FMD) (time frame: Day 1). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04731987, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.

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