HypercholesterolemiaNCT03469518
Effect of β-cryptoxanthin (β-Cx), Plant Sterols and Galactooligosaccharides on Systemic and Gastrointestinal Markers
A study testing β-Cx plus PS plus GOS and β-Cx plus PS in people with Hypercholesterolemia and Osteoporosis, run by Puerta de Hierro University Hospital.
Trial summary
Regular consumption of a beverage containing β-cryptoxanthin (β-Cx) and plant sterols (PS) has been shown to exert a synergic effect in reducing some markers of cardiovascular risk and bone-remodeling (formation and resorption). Read more about this study
- Who is it for?
- Ages 45 to 65 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Hypercholesterolemia, Osteoporosis, Postmenopausal Disorder
- What is being tested?
- β-Cx plus PS plus GOS and β-Cx plus PS
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- Jan 2017to Dec 2019
- 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 45 to 65 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age (45-65 years), BMI<35 Kg/m2, amenorrhea over 12 months, non-dieting and non-intake of vitamin D, calcium and ω-3 fatty acids and PS or vitamin-enriched foods or supplements or other dietary bioactive components.
Who cannot join
- Use of vitamins, hormone replacement therapy, fibrates, statins and a weight losing diet, as well as acute inflammation, chronic medication and infection or intercurrent illness capable of affecting the bioavailability or status of the compounds of interest.
About this study
Official title: Systemic and Intestinal Therapeutic Target Bioactivity of a Functional Beverage Containing β-cryptoxanthin (β-Cx), Plant Sterols (PS) and Galactooligosaccharides (GOS): "in Vivo" and "in Vitro" Studies.
Regular consumption of a beverage containing β-cryptoxanthin (β-Cx) and plant sterols (PS) has been shown to exert a synergic effect in reducing some markers of cardiovascular risk and bone-remodeling (formation and resorption). The present project aims to:
- Evaluate (by in vivo and in vitro studies) the bioavailability of added β-Cx, PS and galactooligosaccharides (GOS) and its stability in the beverage employed in the proposed study.
- Study the biological effect (bioefficacy) associated with the regular consumption of modified milk-based fruit beverages containing β-Cx, PS and GOS in post-menopausal women (target group) by assessing changes in inflammation, cardiovascular and bone turnover biochemical markers.
- Characterize genetic variability (polymorphisms), genetic expression and DNA oxidative damage in the target group as determinants of bioavailability and biological effects of β-Cx, PS and GOS.
- Evaluate the potential prebiotic effect associated to regular consumption of a beverage supplemented with β-Cx, PS and GOS: including "in vitro" studies and characterization of subjects' microbiota and possible microbiota changes associated to the beverage consumption.
Read the detailed description
A previous Clinical Trial (AGL2012-39503-C02) evidenced the beneficial synergic effects upon bone remodeling and cardiovascular risk of a beverage, based on juice and milk, and enriched with PS and β-Cx. "In vitro" and "in vivo" (clinical) studies have confirmed low absorption of PS and β-Cx in this beverage, with possible slight modification of the sterols and metabolites by the intestinal microbiota. PS and β-Cx can reach the colon and be transformed by the intestinal microbiota with resulting beneficial effects.
The new Clinical Trial aims to determine whether the presence of galactooligosaccharides (GOS) in a beverage containing PS and β-Cx might modulate the biological effects of these latter components at either intestinal level (modification of microbiota and inflammatory markers) or systemically (blood cholesterol-lowering effect and bone turnover).
In the present clinical interventional study we will evaluate the systemic biological effects of a beverage containing GOS, PS and β-Cx, as well as its intestinal effects and its influence on the microbiota in postmenopausal women. Furthermore, we will study the stability and bioavailability of PS and β-Cx in the beverage.
The clinical study will help to confirm whether the new GOS-containing beverage has effects upon cardiovascular risk markers, bone remodeling and inflammation at least equivalent to those observed with the beverage studied in the previous Clinical Trial.
The results obtained will generate interesting information for improving beverage formulation with bioactive components that might be relevant for food industry. Furthermore, clarifying the beneficial effects of the studied beverages is relevant not only for healthy subjects but also for those with certain disease conditions (i.e., intestinal inflammation diseases), and may contribute to improve their wellbeing and health, with the consequent social and economic benefits.
DESIGN OF THE CLINICAL STUDY:
Single and combined randomized, double-blind, crossover multiple-dose supplementation trial will be carried out with two beverages (250 ml/day): PS-enriched skimmed milk based fruit beverage rich in β-Cx (sham beverage) and a similar skimmed milk based fruit beverage rich in PS and β-Cx supplemented with GOS (active beverage),as diet supplementation in healthy post-menopausal women.
The Clinical study will take place at the Vitamins Unit of the Clinical Biochemistry Service of the Hospital Universitario Puerta de Hierro-Majadahonda (Madrid, Spain).
Sample size assessment:
The sample size was calculated taking into account the results of total PS and cholesterol obtained in a previous clinical trial (no. NCT01074723). From previous assumption we choose the more conservative option to assure detection of a 7% reduction of cholesterol levels in a mild hypercholesterolemic subjects (e.g. 15 mg/dl) with a type I error of 0.05 and a statistical power of 80%. Furthermore, taking into account that 45% of western population might presented some polymorphisms implicated in the cholesterol absorption process, and assuming a drop-out of 10%, the final sample size should included 40 subjects.
Standard Operating procedures:
Two periods of intervention of 6 weeks separated by a wash-out period of 4 weeks.
During the first trial period, 20 subjects daily will consume the active beverage and 20 subjects will consume the sham beverage for 6 weeks, and after a what-out period of 4 weeks, the type of beverage to be consume during other 6 weeks period will be change (two-by-two cross over assignment). All participants receive sham beverage and active beverage B at some point during the trial but in a different order, depending on the group to which they are assigned.
Sample collection (serum and faeces) will be performed before and after each 6 weeks treatment periods.
All subjects should give written consent to participate in the trial.
The participants will be provided with a list of foods and beverage rich in β-Cx to be avoided during the trial period and will be asked not to change its usual diet and physical activity, to record any side effects during the study, and to complete a semi-quantitative Food Frequency Questionnaire (FFQ) at the end of each intervention period. Question on the organoleptic properties of the beverages will also be included.
- Conditions
- Hypercholesterolemia, Osteoporosis, Postmenopausal Disorder
- Being tested
- β-Cx plus PS plus GOS, β-Cx plus PS
- Keywords
- beta-cryptoxanthin, cholesterol, Galactooligosaccharides, Plant Sterols, Cardiovascular risk, Bone Turnover markers, Intestinal Inflammatory markers, Microbiota
- Medical subject headings
- Hypercholesterolemia, Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
β-Cx plus PS plus GOSDietary supplement
β-Cx plus PSDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| β-Cx plus PS | Sham comparator | Fruit and milk based beverage enriched with beta-cryptoxanthin and plant sterols Receives: Dietary Supplement: β-Cx plus PS |
| β-Cx plus PS plus GOS | Active comparator | Fruit and milk bases beverage enriched with beta-criptoxanthin, plant sterols and galactooligosaccharides Receives: Dietary Supplement: β-Cx plus PS plus GOS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum levels of β-Cx
Measured: 6 weeks
Serum levels of PS
Measured: 6 weeks
Secondary outcomes (8)
Serum lipid profile
Measured: 6 weeks
C reactive protein, ferritin, calprotectin, alpha-1-antitrypsin, alpha-1-acid
Cardiovascular and inflammation risk markers
Measured: 6 weeks
Beta C-terminal telopeptide (beta-CrossLaps/betaCTx), osteoprotegerin, Parathyroid hormone (PTH), calcium, phosphorus, Alkaline phosphatase
Bone markers
Measured: 6 weeks
Sterol fecal levels
Measured: 6 weeks
β-cryptoxanthin fecal levels
Measured: 6 weeks
Interleukins
Measured: 6 weeks
beta-carotene oxygenase 1 (BCO1), beta-carotene oxygenase 2 (BCO2), scavenger receptor class B type I (SR-BI), NPC1L1, ATP-binding cassette (ABC) transporters G5 and G8 (ABCG5 and ABCG8) genes
Intestinal transporters polymorphisms.
Measured: 6 weeks
Taxonomic profiles of microbial communities by ribosomal RNA (16SrRNA) gene metagenomic studies. Microbiota characterization.
Microbiota characterization.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2018
- Study startJan 2017
- Primary completionJul 2017
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypercholesterolemiaStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Crossover Assigment
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Puerta de Hierro University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Nutrition and Food Science Area, Faculty of Pharmacy, University of Valencia, Global Technology centro, Hero Group
- Responsible party
- Principal investigator, Fernando Granado Lorencio, Puerta de Hierro University Hospital
- Investigators
- Fernando Granado Lorencio, PhD, Principal investigator, Hospital Universitario Puerta de Hierro Majadahonda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03469518
- Sponsor's protocol ID
- AGL2015-68006-C2-2-R
- Status last verified
- May 2019
- First submitted
- 19 Feb 2018
- Last updated
- 9 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systemic and Intestinal Therapeutic Target Bioactivity of a Functional Beverage Containing β-cryptoxanthin (β-Cx), Plant Sterols (PS) and Galactooligosaccharides (GOS): "in Vivo" and "in Vitro" Studies.
- ClinicalTrials.gov ID
- NCT03469518
- Acronym / sponsor ID
- AGL2015-68006-C2-2-R
- Conditions
- Hypercholesterolemia, Osteoporosis, Postmenopausal Disorder
- Keywords
- beta-cryptoxanthin, cholesterol, Galactooligosaccharides, Plant Sterols, Cardiovascular risk, Bone Turnover markers, Intestinal Inflammatory markers, Microbiota
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Puerta de Hierro University HospitalUniversity, hospital or other
- Collaborators
- Nutrition and Food Science Area, Faculty of Pharmacy, University of Valencia, Global Technology centro, Hero Group
- Study start
- Jan 2017 (actual)
- Primary completion
- Jul 2017 (actual)
- Study completion
- Dec 2019 (estimated)
- First posted
- 19 Mar 2018 (actual)
- 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.
Regular consumption of a beverage containing β-cryptoxanthin (β-Cx) and plant sterols (PS) has been shown to exert a synergic effect in reducing some markers of cardiovascular risk and bone-remodeling (formation and resorption). The present project aims to:
- Evaluate (by in vivo and in vitro studies) the bioavailability of added β-Cx, PS and galactooligosaccharides (GOS) and its stability in the beverage employed in the proposed study.
- Study the biological effect (bioefficacy) associated with the regular consumption of modified milk-based fruit beverages containing β-Cx, PS and GOS in post-menopausal women (target group) by assessing changes in inflammation, cardiovascular and bone turnover biochemical markers.
- Characterize genetic variability (polymorphisms), genetic expression and DNA oxidative damage in the target group as determinants of bioavailability and biological effects of β-Cx, PS and GOS.
- Evaluate the potential prebiotic effect associated to regular consumption of a beverage supplemented with β-Cx, PS and GOS: including "in vitro" studies and characterization of subjects' microbiota and possible microbiota changes associated to the beverage consumption.
Detailed description
A previous Clinical Trial (AGL2012-39503-C02) evidenced the beneficial synergic effects upon bone remodeling and cardiovascular risk of a beverage, based on juice and milk, and enriched with PS and β-Cx. "In vitro" and "in vivo" (clinical) studies have confirmed low absorption of PS and β-Cx in this beverage, with possible slight modification of the sterols and metabolites by the intestinal microbiota. PS and β-Cx can reach the colon and be transformed by the intestinal microbiota with resulting beneficial effects.
The new Clinical Trial aims to determine whether the presence of galactooligosaccharides (GOS) in a beverage containing PS and β-Cx might modulate the biological effects of these latter components at either intestinal level (modification of microbiota and inflammatory markers) or systemically (blood cholesterol-lowering effect and bone turnover).
In the present clinical interventional study we will evaluate the systemic biological effects of a beverage containing GOS, PS and β-Cx, as well as its intestinal effects and its influence on the microbiota in postmenopausal women. Furthermore, we will study the stability and bioavailability of PS and β-Cx in the beverage.
The clinical study will help to confirm whether the new GOS-containing beverage has effects upon cardiovascular risk markers, bone remodeling and inflammation at least equivalent to those observed with the beverage studied in the previous Clinical Trial.
The results obtained will generate interesting information for improving beverage formulation with bioactive components that might be relevant for food industry. Furthermore, clarifying the beneficial effects of the studied beverages is relevant not only for healthy subjects but also for those with certain disease conditions (i.e., intestinal inflammation diseases), and may contribute to improve their wellbeing and health, with the consequent social and economic benefits.
DESIGN OF THE CLINICAL STUDY:
Single and combined randomized, double-blind, crossover multiple-dose supplementation trial will be carried out with two beverages (250 ml/day): PS-enriched skimmed milk based fruit beverage rich in β-Cx (sham beverage) and a similar skimmed milk based fruit beverage rich in PS and β-Cx supplemented with GOS (active beverage),as diet supplementation in healthy post-menopausal women.
The Clinical study will take place at the Vitamins Unit of the Clinical Biochemistry Service of the Hospital Universitario Puerta de Hierro-Majadahonda (Madrid, Spain).
Sample size assessment:
The sample size was calculated taking into account the results of total PS and cholesterol obtained in a previous clinical trial (no. NCT01074723). From previous assumption we choose the more conservative option to assure detection of a 7% reduction of cholesterol levels in a mild hypercholesterolemic subjects (e.g. 15 mg/dl) with a type I error of 0.05 and a statistical power of 80%. Furthermore, taking into account that 45% of western population might presented some polymorphisms implicated in the cholesterol absorption process, and assuming a drop-out of 10%, the final sample size should included 40 subjects.
Standard Operating procedures:
Two periods of intervention of 6 weeks separated by a wash-out period of 4 weeks.
During the first trial period, 20 subjects daily will consume the active beverage and 20 subjects will consume the sham beverage for 6 weeks, and after a what-out period of 4 weeks, the type of beverage to be consume during other 6 weeks period will be change (two-by-two cross over assignment). All participants receive sham beverage and active beverage B at some point during the trial but in a different order, depending on the group to which they are assigned.
Sample collection (serum and faeces) will be performed before and after each 6 weeks treatment periods.
All subjects should give written consent to participate in the trial.
The participants will be provided with a list of foods and beverage rich in β-Cx to be avoided during the trial period and will be asked not to change its usual diet and physical activity, to record any side effects during the study, and to complete a semi-quantitative Food Frequency Questionnaire (FFQ) at the end of each intervention period. Question on the organoleptic properties of the beverages will also be included.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Crossover Assigment
| Arm | Type | Receives |
|---|---|---|
| β-Cx plus PS | Sham comparator | Dietary Supplement: β-Cx plus PSFruit and milk based beverage enriched with beta-cryptoxanthin and plant sterols |
| β-Cx plus PS plus GOS | Active comparator | Dietary Supplement: β-Cx plus PS plus GOSFruit and milk bases beverage enriched with beta-criptoxanthin, plant sterols and galactooligosaccharides |
Who may qualify
- Ages
- 45 to 65 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Age (45-65 years), BMI<35 Kg/m2, amenorrhea over 12 months, non-dieting and non-intake of vitamin D, calcium and ω-3 fatty acids and PS or vitamin-enriched foods or supplements or other dietary bioactive components.
Key exclusion criteria (1 listed)
- Use of vitamins, hormone replacement therapy, fibrates, statins and a weight losing diet, as well as acute inflammation, chronic medication and infection or intercurrent illness capable of affecting the bioavailability or status of the compounds of interest.
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 |
|---|---|---|
| β-Cx plus PS plus GOS | Dietary supplement | β-Cx plus PS plus GOS |
| β-Cx plus PS | Dietary supplement | β-Cx plus PS |
Primary outcome
Serum levels of β-Cx
Time frame: 6 weeks
Serum levels of PS
Time frame: 6 weeks
8 secondary outcomes
Serum lipid profile
Time frame: 6 weeks
C reactive protein, ferritin, calprotectin, alpha-1-antitrypsin, alpha-1-acid
Time frame: 6 weeks
Beta C-terminal telopeptide (beta-CrossLaps/betaCTx), osteoprotegerin, Parathyroid hormone (PTH), calcium, phosphorus, Alkaline phosphatase
Time frame: 6 weeks
Sterol fecal levels
Time frame: 6 weeks
β-cryptoxanthin fecal levels
Time frame: 6 weeks
Interleukins
Time frame: 6 weeks
beta-carotene oxygenase 1 (BCO1), beta-carotene oxygenase 2 (BCO2), scavenger receptor class B type I (SR-BI), NPC1L1, ATP-binding cassette (ABC) transporters G5 and G8 (ABCG5 and ABCG8) genes
Time frame: 6 weeks
Taxonomic profiles of microbial communities by ribosomal RNA (16SrRNA) gene metagenomic studies. Microbiota characterization.
Time frame: 6 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2019.
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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.
Fernando Granado Lorencio, PhD principal investigator
Hospital Universitario Puerta de Hierro Majadahonda
Questions about this trial
What is this clinical trial studying?
A study testing β-Cx plus PS plus GOS and β-Cx plus PS in people with Hypercholesterolemia and Osteoporosis, run by Puerta de Hierro University Hospital.
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 1 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 9 May 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
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?
Serum levels of β-Cx (time frame: 6 weeks). The study lists 2 primary outcomes in all. 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 9 May 2019.