Cardiovascular Risk FactorsPhase 3CITRUSNCT02479568
Beneficial Impact of Orange Juice Consumption on Risk Factors Associated With Cardiovascular Diseases
A Phase 3 study testing 100% Florida OJ and 100% Florida OJ-enriched in people with Cardiovascular Risk Factors, run by Technological Centre of Nutrition and Health, Spain at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Risk Factors
- What is being tested?
- 100% Florida OJ and 100% Florida OJ-enriched
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 159 participants
- Where
- 1 siteSpain
- Study dates
- 12 Jan 2016to 6 Jul 2017
- Phase
- Phase 3
- 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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Technological Centre of Nutrition and Health (CTNS)
Reus, Tarragona, 43204
About this study
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
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.
Read the 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.
- Conditions
- Cardiovascular Risk Factors
- Being tested
- Control, 100% Florida OJ, 100% Florida OJ-enriched
- Keywords
- Cardiovascular disease, biomarkers, transcriptomics, orange juice, hesperidin, systolic blood pressure, metabolomics, cardiovascular risk factor
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ControlDietary supplement
500 mL (250 mL; 2 times/day) of placebo drink for 12 weeks
100% Florida OJDietary supplement
500 mL (250 mL; 2 times/day) of 100% Florida OJ for 12 weeks
100% Florida OJ-enrichedDietary supplement
500 mL (250 mL; 2 times/day) of 100% Florida OJ-enriched for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Control | Active comparator | Control drink (placebo) Receives: Dietary Supplement: Control |
| Natural Florida orange juice | Experimental | 100% Florida orange juice (OJ) (natural content of hesperidin) Receives: Dietary Supplement: 100% Florida OJ |
| Enriched Florida orange juice | Experimental | 100% Florida orange juice (OJ) (enriched hesperidin content) Receives: Dietary Supplement: 100% Florida OJ-enriched |
What is being measured
The primary outcome is the main question the study is designed to answer.
Systolic Blood Pressure
During each visit, SBP will be measured after 5 min in a seated position in a comfortable room by the physician. The measurement will be taken in duplicate at 1-min intervals using an automatic sphygmomanometer (OMRON HEM-907; Peroxfarma, Barcelona, Spain), and the average of the two measurements will be calculated.
Measured: Every 2 weeks for a total of 12 weeks.
Secondary outcomes (6)
Diastolic Blood Pressure
During each visit, diastolic BP will be measured after 5 min in a seated position in a comfortable room by the physician. The measurement will be taken in duplicate at 1-min intervals using an automatic sphygmomanometer (OMRON HEM-907; Peroxfarma, Barcelona, Spain), and the average of the two measurements will be calculated.
Measured: Every 2 weeks for a total of 12 weeks.
Ischemic reactive hyperemia (IRH)
The endothelial-dependent vasomotor functions will be measured as IRH by a Laser-Doppler linear Periflux 5000 flowmeter (Perimed AB, Järfälla, Stockholm, Sweden)
Measured: Every 4 weeks for a total of 12 weeks
Platelet aggregation
Multiplate analyzer, Roche
Measured: Every 4 weeks for a total of 12 weeks
Homocysteine
Homocysteine concentrations will be measured by liquid chromatography-mass spectrometry (LC-MS/MS)
Measured: Every 4 weeks for a total of 12 weeks
C-reactive protein (inflammatory marker)
High sensitivity C-reactive protein (hsCRP) by standardized methods in a Cobas Mira Plus autoanalyzer (Roche Diagnostics Systems, Madrid, Spain)
Measured: Every 4 weeks for a total of 12 weeks
oxidized LDL (as oxidative stress biomarker)
Mercodia Oxidized LDL ELISA kit will be used to measure the oxidized LDL (mU/L).
Measured: Every 4 weeks for a total of 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2015 (estimated)
- Study start12 Jan 2016
- Primary completion6 Jul 2017
- Study completion6 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular Risk FactorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 159 participants (actual)
Sponsor and investigators
- Lead sponsor
- Technological Centre of Nutrition and Health, Spain
- Sponsor type
- University, hospital or other
- Collaborators
- Florida Department of Citrus, Technological Centre of Nutrition and Health, Hospital Universitari Sant Joan de Reus, University Rovira i Virgili
- Responsible party
- Sponsor
- Investigators
- Rosa Solà Alberich, Prof, MD, Principal investigator, • University Rovira i Virgili / Hospital Universitari Sant Joan de Reus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02479568
- Sponsor's protocol ID
- CITRUS 14-12
- Acronym
- CITRUS
- Status last verified
- Feb 2022
- First submitted
- 17 Jun 2015
- Last updated
- 28 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02479568
- Acronym / sponsor ID
- CITRUS / CITRUS 14-12
- Conditions
- Cardiovascular Risk Factors
- Keywords
- Cardiovascular disease, biomarkers, transcriptomics, orange juice, hesperidin, systolic blood pressure, metabolomics, cardiovascular risk factor
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 159 participants (actual)
- Lead sponsor
- Technological Centre of Nutrition and Health, SpainUniversity, hospital or other
- Collaborators
- Florida Department of Citrus, Technological Centre of Nutrition and Health, Hospital Universitari Sant Joan de Reus, University Rovira i Virgili
- Study start
- 12 Jan 2016
- Primary completion
- 6 Jul 2017 (actual)
- Study completion
- 6 Jul 2017 (actual)
- First posted
- 24 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control | Active comparator | Dietary Supplement: ControlControl drink (placebo) |
| Natural Florida orange juice | Experimental | Dietary Supplement: 100% Florida OJ100% Florida orange juice (OJ) (natural content of hesperidin) |
| Enriched Florida orange juice | Experimental | Dietary Supplement: 100% Florida OJ-enriched100% Florida orange juice (OJ) (enriched hesperidin content) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Control500 mL (250 mL; 2 times/day) of placebo drink for 12 weeks | Dietary supplement | Control |
| 100% Florida OJ500 mL (250 mL; 2 times/day) of 100% Florida OJ for 12 weeks | Dietary supplement | Natural Florida orange juice |
| 100% Florida OJ-enriched500 mL (250 mL; 2 times/day) of 100% Florida OJ-enriched for 12 weeks | Dietary supplement | Enriched Florida orange juice |
Primary outcome
Systolic Blood Pressure
Time frame: Every 2 weeks for a total of 12 weeks.
During each visit, SBP will be measured after 5 min in a seated position in a comfortable room by the physician. The measurement will be taken in duplicate at 1-min intervals using an automatic sphygmomanometer (OMRON HEM-907; Peroxfarma, Barcelona, Spain), and the average of the two measurements will be calculated.
6 secondary outcomes
Diastolic Blood Pressure
Time frame: Every 2 weeks for a total of 12 weeks.
Ischemic reactive hyperemia (IRH)
Time frame: Every 4 weeks for a total of 12 weeks
Platelet aggregation
Time frame: Every 4 weeks for a total of 12 weeks
Homocysteine
Time frame: Every 4 weeks for a total of 12 weeks
C-reactive protein (inflammatory marker)
Time frame: Every 4 weeks for a total of 12 weeks
oxidized LDL (as oxidative stress biomarker)
Time frame: Every 4 weeks for a total of 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2022.
- Technological Centre of Nutrition and HealthLink provided by the sponsor.
- Florida Department of CitrusLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rosa Solà Alberich, Prof, MD principal investigator
• University Rovira i Virgili / Hospital Universitari Sant Joan de Reus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 100% Florida OJ and 100% Florida OJ-enriched in people with Cardiovascular Risk Factors, run by Technological Centre of Nutrition and Health, Spain at 1 site in Spain.
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 5 inclusion and 16 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 28 Feb 2022. 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 Spain. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Systolic Blood Pressure (time frame: Every 2 weeks for a total of 12 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Feb 2022.