Condition category
Nutritional, Metabolic, Endocrine
Date applied
07/11/2017
Date assigned
09/11/2017
Last edited
10/11/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Metabolic syndrome is a serious risk factor for cardiovascular disease (heart disease) such as arteriosclerosis and is caused by hyperlipidemia (high levels of lipids in the blood), hyperglycemia (high blood sugar), and hypertension (high blood pressure). Arteriosclerosis (the thickening and hardening of the artery walls) is related to cardiovascular disease and cerebral infarction (when there is a blockage of the arteries that deliver blood to the brain), which are widely recognized as major public health problems. Reducing the risk of arteriosclerosis, especially dyslipidemia (abnormal amount of lipids in the blood), which was reported to be the strongest risk factor for arteriosclerosis, is extremely important. In some patients, the major abnormality in dyslipidemia is a postprandial serum triglyceride and cholesterol elevation (high levels of sugar and cholesterol after eating). In previous reports, administration of tea polyphenols (micronutrients) improved blood lipid levels and promoted lipid excretion in an animal study, while prevented postprandial serum triglyceride elevation in a clinical study. These reports suggest that tea polyphenols have a lipid excretion (removal) effect. Previous authors have demonstrated that the addition of tea catechins (a natural type of phenol and antioxidant) galloyl moiety to a bile salt micellar solution precipitated (separated) cholesterol and decreased the micellar solubility of cholesterol in a dose-dependent manner. In contrast, green tea catechins without a galloyl moiety did not precipitated cholesterol. Interestingly, apple procyanidins (apple polyphenols) are oligomeric (consisting of only a few) compounds consisting of catechin monomeric units. Specifically, dimeric procyanidins are the most structurally similar to the green tea catechins with a galloyl moiety. Therefore, it could be hypothesised that these may play a major role as regards our observed effects of apple extract samples on in vitro cholesterol micellar solubility. Specifically, the antioxidant composition and in vitro effects on cholesterol metabolism of polyphenolic extracts from Annurca apple, has been evaluated. By comparing experimental data with those from more common commercial apple cultivars, Annurca apple exhibited the highest polyphenolic concentration, while results obtained by incubating human hepatocellular liver carcinoma (HepG2) cell lines with apple extracts, indicated Annurca apple as the most effective in reducing cell cholesterol uptake, enhancing LDL-C receptor binding activity, and increasing cell medium Apo-AI concentration. The aim of the present study is to evaluate the effects of Annurca apple polyphenolic extract on intestinal cholesterol solubility in healthy subjects.

Who can participate?
Men and women between 18-83 years of age.

What does the study involve?
Participants are provided with a food frequency questionnaire at the beginning of the study. Participants are randomly divided into two groups (each one of 25 subjects, 15 men and 10 women).
They are followed by a cross-over design including 7-day washout periods and 10-day treatment periods. During the treatment periods, each group are given about 370 mg cholesterol a day from two eggs (about 50 g weight each) (185 mg cholesterol each within 30 min after lunch and dinner) and total 1000 mg Annurca apple polyphenolic extract in gastro-resistant capsules at two meals (one 500 mg capsule at each meal). Subjects are allowed to take water freely. All the participants are instructed to maintain their habitual patterns of physical activity throughout the entire study period. The physical characteristics are measured and 1 mL of blood is collected after 12 h fasting in the early morning. The blood samples are collected for biochemical examination at days 8, 18, 25 and 35 of the study period. Fecal samples are collected for the analysis of lipid excretion during the last three days of each treatment period.

What are the possible benefits and risks of participating?
In line with what already reported in literature as regards the effects of apple polyphenols, participants are expected to reveal a positive influence on the balance regarding the circulating lipoproteins. Conversely, no side effects are expected, since the maximum quantity of apple polyphenolic extracts (1000 mg) administered daily is in full accordance with the maximum polyphenolic extract daily intake, through food supplements and novel foods, indicated by the revised form (January 2015) of the Commission Regulation (EC) No. 258/1997, as the safe polyphenolic daily amount compatible with a good health state.

Where is the study run from?
The blood samples are collected by the Samnium Medical Cooperative (Italy) and analysed at the Department of Pharmacy, University of Naples “Federico II” (Italy).

When is the study starting and how long is it expected to run for?
October 2017 to January 2018

Who is funding the study?
1. Samnium Medical Cooperative (Italy)
2. University of Naples “Federico II” (Italy)

Who is the main contact?
Professor Gian Carlo Tenore

Trial website

Contact information

Type

Scientific

Primary contact

Prof Gian Carlo Tenore

ORCID ID

http://orcid.org/0000-0002-0251-9936

Contact details

University of Naples
Via Domenico Montesano
49
Naples
80131
Italy
+39 (0)81678610
giancarlo.tenore@unina.it

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

123501

Study information

Scientific title

Effects of Annurca apple polyphenolic extract on intestinal cholesterol solubility in healthy subjects: A monocentric, double-blind, randomised, placebo-controlled, cross-over study

Acronym

AMD

Study hypothesis

Annurca apple contains oligomeric procyanidins, mainly dimeric compounds, which are structurally similar to tea galloylated catechins for which the capacity to decrease intestinal cholesterol solubility has been demonstrated. Thus,
Aim 1: Evaluate the effects of Annurca apple polyphenolic extract on fecal cholesterol levels in the subjects.
Aim 2: Evaluate the effects of Annurca apple polyphenolic extract on plasma levels of TC, LDL-C, HDL-C, TG, in the subjects.

Ethics approval

Azienda Ospedaliera Gaetano Rummo Via dell’Angelo, 18/10/2017, ref: 123501

Study design

Dietary intervention trial parallel randomised cross-over open controlled study

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet: Gian Carlo Tenore giancarlo.tenore@unina.it

Condition

Metabolic Syndrome (MeTS)

Intervention

Participants are randomly allocated into two groups.

They are followed by a cross-over design including 7-day washout periods and 10-day treatment periods. During the treatment periods, each group are given about 370 mg cholesterol a day from two eggs (about 50 g weight each) (185 mg cholesterol each within 30 min after lunch and dinner) and total 1000 mg Annurca apple polyphenolic extract in gastro-resistant capsules at two meals (one 500 mg capsule at each meal).

Intervention type

Supplement

Phase

Drug names

Primary outcome measure

Fecal samples are collected for the analysis of lipid excretion during the last three days of each treatment period.

Secondary outcome measures

1. Clinical history is measured both by interviews and previous clinical data at baseline
2. Anthropometric measures are collected taking height and weight at baseline and at the end of the study period
3. Nutrient intake and dietary habits are measured using a seven day food record validated nutritional questionnaire at baseline and at the end of the study period
4. Blood pressure is measured using a blood pressure cuff at baseline and at the end of the study period
5. 24 hour ambulatory blood pressure is measured using blood pressure cuff at baseline and at the end of the study period
6. Plasma TC is measured using a Diacron International Free Carpe Diem spectrophotometer (Grosseto, Italy), and commercially available kits from Diacron International at days 8, 18, 25 and 35 of the study period
7. HDL-C is measured using a Diacron International Free Carpe Diem spectrophotometer (Grosseto, Italy), and commercially available kits from Diacron International at days 8, 18, 25 and 35 of the study period
8. LDL-C is measured using a Diacron International Free Carpe Diem spectrophotometer (Grosseto, Italy), and commercially available kits from Diacron International at days 8, 18, 25 and 35 of the study period
9. Triglyceride levels are measured using a Diacron International Free Carpe Diem spectrophotometer (Grosseto, Italy), and commercially available kits from Diacron International at days 8, 18, 25 and 35 of the study period
10. Blood analysis (AST, ALT, γ-GTP, ALP, LDH, Albumin, Total bilirubin, Creatinine) is measured using a Diacron International Free Carpe Diem spectrophotometer (Grosseto, Italy), and commercially available kits from Diacron International at days 8, 18, 25 and 35 of the study period

Overall trial start date

18/10/2017

Overall trial end date

04/01/2018

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Men and women between 18-83 years of age, of white race, with the following range values of serum cholesterol parameters at baseline (week 0):
1. TC, 200-260 mg/dL
2. HDL-C, 30-45 mg/dL
3. LDL-C, 189-206 mg/dL
4. TG, 170-280 mg/dL
5. Body mass index (BMI) between 18 and 30 kg/m2

Participant type

Healthy volunteer

Age group

Mixed

Gender

Both

Target number of participants

50

Participant exclusion criteria

Healthy adults (males and females) with:
1. Smoking
2. Obesity (BMI >30 kg/m2)
3. Diabetes
4. Hepatic disease
5. Renal disease
6. Heart disease
7. Family history of chronic diseases
8. Drug therapy or supplement intake for hypercholesterolemia
9. Drug therapy or supplement intake containing apple polyphenols
10. Heavy physical exercise (>10 h/week)
11. Pregnant women, women suspected of being pregnant, women who hoped to become pregnant, breastfeeding
12. Birch pollen allergy
13. Use of vitamin/mineral supplements 2 weeks prior to entry into the study
14. Donation of blood less than 3 months before the study

Recruitment start date

17/11/2017

Recruitment end date

27/11/2017

Locations

Countries of recruitment

Italy

Trial participating centre

Samnium Medical Cooperative
(Benevento, Italy) Viale C. Colombo, 18
Castelvenere
80131
Italy

Trial participating centre

University of Naples “Federico II” (lead centre)
Department of Pharmacy via Domenico Montesano, 49
Naples
80131
Italy

Sponsor information

Organisation

Samnium Medical Cooperative

Sponsor details

Viale C. Colombo
18 - 82037 Castelvenere (BN)
Benevento
82037
Italy
+39 (0)82424244
samnium@samnium.com

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Hospital/treatment centre

Funder name

Samnium Medical Cooperative

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal. Additional documents will be available at the Department of Pharmacy, University of Naples “Federico II”, Naples, Italy.

IPD sharing statement:
The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository at the Department of Pharmacy, University of Naples “Federico II”.

Intention to publish date

07/01/2019

Participant level data

Stored in repository

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

10/11/2017: Internal review.