Clinical trial NCT03795324: Red-fleshed Apple as a Novel Anthocyanin-biofortified Food to Improve Cardiometabolic Risk Factors.
Official title: Red-fleshed Apple as a Novel Anthocyanin-biofortified Food to Improve Cardiometabolic Risk Factors: Innovation in Crop and Application to Health.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: High LDL-cholesterol Levels
Keywords: Anthocyanins
apple
biofortification
cardiometabolic
LDL cholesterol
polyphenols
Lead sponsor: University Rovira i Virgili
Sponsor class: OTHER
Collaborators: name: Universitat de Lleida
name: Ministerio de Ciencia e Innovación, Spain
First posted: 2019-01-07
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary aim is to evaluate the added health value of the presence of anthocyanins in the redlove apple, versus a green apple with a similar matrix, on cardiometabolic risk, and compare the matrix effect on the bioavailability of anthocyanins, and its effect on cardiometabolic risk factors, in two different products with a similar phenolic and anthocyanin content: the redlove apple and an aronia drink.

Detailed description: The worldwide high prevalence of cardiovascular disease (CVD) requires lifestyle changes and new dietary prevention strategies based on the increased intake of foods rich in bioactive compounds, as they are considered as key mediators in the improvement of CVD risk factors.

Regarding the health impact on anthocyanins in cardiometalic risk factors and CVD, it has been reported that the dietary intake of anthocyanidins, among other classes of flavonoids, is inversely associated with the risk of CVD in both European and US population. A recent systematic review of human randomized controlled trials assessing the impact of anthocyanins on CVD markers concluded that one of the main modulated outcomes is the decrease of serum LDLc. However, diet does not appear to be sufficient to guarantee the necessary intake to obtain the health benefits specified. Due to previous positive results, a new dietetic strategy based on biofortification to enhance the levels of phenolic compounds is proposed in the present project.

The primary aim is to evaluate the added health value of the presence of anthocyanins in the redlove apple, versus a green apple with a similar matrix, on cardiometabolic risk, and compare the matrix effect on the bioavailability of anthocyanins and its effect on cardiometabolic risk factors, in two different products with a similar phenolic and anthocyanin content: the redlove apple and an aronia drink.

Participants will be 120 free-living volunteers (men and women) with high LDL-cholesterol levels (LDL-cholesterol levels ≥115 mg/dl and ≥190 mg/dl) who will be assigned to one of the three arms for 6-week period of dietary treatment. The design of the intervention study is controlled, parallel and randomized. The intervention will combine acute (post-prandial) and chronic effects.

The sample size was computed to be sufficient to detect differences between treatment groups regarding the evolution in time of LDL-cholesterol levels. Justification of chosen sample size is based on assuming a 0.50mmol/l (approximately 15%) post-intervention difference of LDL-cholesterol and a 0.72mmol/l Standard deviation (SD), with α=0.05 and 1-β=0.08 a minimum of 22 participants were required. However the sample size will be 40 participants for arm, in total 120 subjects.

For the acute study, the investigators have chosen n=10 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.

Eligibility criteria: Inclusion Criteria:

* Men and women over 18 years old.
* LDL-cholesterol levels ≥115 mg/dl and ≥190 mg/dl.
* Sign the informed consent provided before the initial screening visit.

Exclusion Criteria:

* LDL-cholesterol levels ≤115 mg/dl and \<190 mg/dl.
* Use of hypolipemiant treatment (drugs and functional foods), or hypoglucaemiant treatment.
* Having diabetes mellitus type 1 or type 2.
* BMI values ≥35kg/m2.
* Present triglycerides levels ≥350mg/dl.
* Presenting anemia (hemoglobin ≤13g/dl in men and ≤12g/dl in women).
* Subjects diagnosed of intestinal disorders such as Chron disease, colitis ulcerous, celiac disease and irritable bowel syndrome.
* Present fructose and/or sorbitol and/or gluten intolerance.
* Present clinical active chronic disease
* Use of antioxidants supplements.
* Being pregnant or intending to become pregnant.
* Be in breastfeeding period.
* Present chronic alcoholism.
* Tobacco use.
* Participate in or have participated in a clinical trial or nutritional intervention study in the last 30 days prior to inclusion in the study.
* Being unable to follow the study guidelines.

Primary outcomes:
measure: Changes in serum LDL-cholesterol (measured in mg/dL)
timeFrame: 6 weeks, week 1 and week 6
Secondary outcomes:
measure: Changes in parameters of body composition (weight measured in kg)
timeFrame: 6 weeks, week 1, week 2, week 4 and week 6
measure: Parameters of body composition (height measured in meters)
timeFrame: 6 weeks, week 1
measure: Changes in parameters of body composition (BMI measured in kg/m2)
timeFrame: 6 weeks, week 1, week 2, week 4 and week 6
measure: Changes in parameters of body composition (waist circumference measured in cm)
timeFrame: 6 weeks, week 1, week 2, week 4 and week 6
measure: Changes in blood pressure (systolic blood pressure and diastolic blood pressure measured in mmHg)
timeFrame: 6 weeks, week 1, week 2, week 4 and week 6
measure: Changes in ischemic reactive hyperemia (IRH measured in perfusion units)
timeFrame: 6 weeks, week 1 and week 6
measure: Changes in lipid plasmatic markers (total cholesterol, HDL cholesterol, triglycerides, non-esterified fatty acids, Apo B100 and Apo A. All these lipid plasmatic markers will be measured in mg/dL)
timeFrame: 6 weeks, week 1 and week 6
measure: Changes in glucose markers (glucose and insulin measured in mg/dL)
timeFrame: 6 weeks, week 1 and week 6
measure: Changes in oxidative markers (LDLox and Endogenous fat soluble antioxidants measured in mg/dL)
timeFrame: 6 weeks, week 1 and week 6
measure: Changes in inflammation markers (c-reactive protein and serum endothelin-1 measured in mg/dL)
timeFrame: 6 weeks, week 1 and week 6
measure: Changes in dietary compliance markers (Phenolic compounds and metabolites measured in mg/L in 24h urine samples)
timeFrame: 6 weeks, week 1 and week 6
measure: Changes in faeces metabolites (Short Chain Fatty Acids, bile acids and sterols measured in mg/L in faeces samples)
timeFrame: 6 weeks, week 1 and week 6
measure: Changes in fecal microbiota composition (relative abundance of the identified operational taxonomic units (OTUs) measured as % change from baseline)
timeFrame: 6 weeks, week 1 and week 6
measure: Changes in lipoprotein profile (number of LDL and HDL particles measured as % change from baseline)
timeFrame: 6 weeks, week 1 and week 6
measure: Changes in cholesterol efflux (measured as % change from baseline)
timeFrame: 6 weeks, week 1 and week 6
Other outcomes:
Locations:
city: Reus
country: Spain
facility: University Rovira i Virgili
state: Tarragona
Study officials:
affiliation: University Rovira i Virgili
name: Rosa Sola, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: