Clinical trial NCT02479568: Beneficial Impact of Orange Juice Consumption on Risk Factors Associated With Cardiovascular Diseases
Official title: Randomized, Parallel and Double Blind Placebo-controlled Study for the Evaluation of Both Acute and Chronic Role of Hesperidin Consumption in 100% Orange Juice
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiovascular Risk Factors
Keywords: Cardiovascular disease
biomarkers
transcriptomics
orange juice
hesperidin
systolic blood pressure
metabolomics
cardiovascular risk factor
Lead sponsor: Technological Centre of Nutrition and Health, Spain
Sponsor class: OTHER
Collaborators: name: Florida Department of Citrus
name: Technological Centre of Nutrition and Health
name: Hospital Universitari Sant Joan de Reus
name: University Rovira i Virgili
First posted: 2015-06-24
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary aim is to examine both the acute and chronic effects of hesperidin consumption from 100% Florida orange juice in various doses on functional and systemic markers associated with cardiovascular disease (CVD) risks.

Detailed description: The aim of this study is to compare the effect of different doses of hesperidin in 100% Florida orange juice (OJ) when regularly or postprandially consumed on cardiovascular risk markers; in addition, the plausible role and mechanism of the hesperidin will be investigated.

The sample size was calculated using a previously available bibliography using systolic blood pressure (SBP) as the primary outcome measure. A total of 84 subjects per study product group were needed, assuming variance components of approximately 20.0, to detect differences between the three groups (control, orange juice and hesperidin-enriched orange juice (10 mm Hg)) with a bilateral significance level of α=0.05 and a power of 80 %.

The sample size was computed to be sufficient to detect differences between treatment groups regarding the evolution in time of SBP levels. Justification of chosen sample size is based on the clinically meaningful difference assigned to δ=10.0 mm Hg, which is equivalent to a difference of approximately 7.4 % in patients with baseline SBP levels of approximately 135 mm Hg. Thus, a sample of 252 participants can be used for the chronic three arm parallel trial design (84 subjects/arm) and will allow us to detect small but clinically relevant differences between the three groups with statistical robustness and direct interpretation in terms of the chronic treatment effect.

To the acute postprandial tests, the investigators have chosen n=20 subjects per arm according to the most studies that have addressed the metabolic effects of a postprandial intervention have been performed using a very similar number of subjects with statistically good quality results.

The statistical analysis will follow the principles specified in the guidelines of the ICHE9 and CPMP/EWP/908/99 ICHE9 Points to Consider on Multiplicity Issues in Clinical Trials.

The continuous efficacy variables will be analyzed by an ANCOVA (analysis of covariance) with the baseline value as a covariate.

The efficacy outcomes will be determined using the absolute values and absolute differences from the baseline. The efficacy analysis will be performed using the Available Data Only approach. In addition, the analysis of the primary efficacy variable will be performed with the Baseline Observation Carried Forward approach.

A suitable hypothesis test will be applied to the rest of the variables according to the nature of each variable, such as the Fisher exact test for categorical variables, Student's T-test for continuous variables and Mann-Whitney U test for ordinal scale variables.

The statistical tests will be applied with an α=0.05 two-sided significance level. Post-hoc analyses and comparisons between pairs of groups will be done as for exploratory purposes.

In addition, the statistical plan will be transferred to the application form of the electronic data collection report (e-CDR), which allows the improvement of data management, diminishes human errors (according threshold values of each outcome) and, overall, guarantees the maximum exploitation of human data in the context of statistical analysis.

Eligibility criteria: Inclusion criteria

* Men or women 18-65 years old
* No evidence of chronic disease
* No familial CVD history
* Written informed consent provided before the initial screening visit.
* Blood pressure (with no drug intervention) \>120 mm Hg systolic blood pressure ≤ 159 mmHg

Exclusion criteria

* Body mass index (BMI) ≥ 35 kg/m2
* Glucose \>125 mg/dl
* Systolic blood pressure ≥ 160 mm Hg and diastolic blood pressure \>100 mm Hg or taking antihypertensive medications
* Total cholesterol \>240 mg/dl
* LDL-cholesterol \>160 md/dl
* TAG \>350
* Smoking
* Pregnant or intending to become pregnant
* Use of medications, antioxidants, or vitamin supplements
* Chronic alcoholism
* Intense physical activity (5h/week)
* Intestinal disorders
* Following of a vegetarian diet
* Anemia (hemoglobin ≤13 g/dL in men and ≤12 g/dL in women)
* Current or past participation in a clinical trial or consumption of a research product in the 30 days prior to inclusion in the study
* Failure to follow the study guidelines.

Primary outcomes:
measure: Systolic Blood Pressure
timeFrame: Every 2 weeks for a total of 12 weeks.
Secondary outcomes:
measure: Diastolic Blood Pressure
timeFrame: Every 2 weeks for a total of 12 weeks.
measure: Ischemic reactive hyperemia (IRH)
timeFrame: Every 4 weeks for a total of 12 weeks
measure: Platelet aggregation
timeFrame: Every 4 weeks for a total of 12 weeks
measure: Homocysteine
timeFrame: Every 4 weeks for a total of 12 weeks
measure: C-reactive protein (inflammatory marker)
timeFrame: Every 4 weeks for a total of 12 weeks
measure: oxidized LDL (as oxidative stress biomarker)
timeFrame: Every 4 weeks for a total of 12 weeks
Other outcomes:
measure: Transcriptomics
timeFrame: At week 0 (V1) and 12 week (V7).
measure: Non-targeted Metabolomics
timeFrame: At week 0 (V1) and 12 week (V7).
Locations:
city: Reus
country: Spain
facility: Technological Centre of Nutrition and Health (CTNS)
state: Tarragona
Study officials:
affiliation: • University Rovira i Virgili / Hospital Universitari Sant Joan de Reus
name: Rosa Solà Alberich, Prof, MD
role: PRINCIPAL_INVESTIGATOR
References: