Protective role of dietary intervention rich in unsaturated fats in dyslipidemic children

ISRCTN	ISRCTN12261900
DOI	https://doi.org/10.1186/ISRCTN12261900
Secondary identifying numbers	Protocol number: EC:CS377

Submission date: 27/04/2016
Registration date: 10/06/2016
Last edited: 14/05/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Regular intake of nuts, naturally rich in monounsaturated fats (MUFA) or other polyunsaturated (PUFA) sources may reduce the risk of developing cardiovascular disease (CVD) and also improve lipid profile (fats and cholesterol in the blood). People with a high level of serum lipids (that is, a lot of fat in the blood) seem to be more susceptible to oxidative stress (damage caused by free radicals) and CVD. They may therefore benefit from an increased nut or MUFA and PUFA intake. The aim of this study is to investigate the effect of hazelnuts eaten as snack or source of polyunsaturated fats (e.g. alpha-linolenic acid) on markers of oxidative stress (that is, substances that show the presence of oxidative stress), inflammation, lipid profile, dietary markers and intestinal microflora (microbiota) composition in children and adolescents with dyslipidemia (abnormal amounts of fat in the blood)

Who can participate?
Children aged 5-17 with dyslipidemia

What does the study involve?
At the beginning of the study, all participants are given dietary guidelines and are randomly allocated to one of three groups. One group eat a daily portion of hazelnuts with skin (15-30 g/Kg, based on body weight), one group eat the same amount of hazelnuts without skin and a control group receive only the dietary guidelines and are not given nuts to eat or a diet otherwise enriched with other sources of unsaturated fats. Blood samples are taken for all participants from all groups at the start of the study and then 8 weeks later for analysis.

What are the possible benefits and risks of participating?
The intake of hazelnuts as a snack is expected to improve the lipid profile and reduce the levels of oxidative stress in children and adolescents with dyslipidemia. There is are expected risks associated with the eating of the hazelnuts.

Where is the study run from?
The University of Turin and University of Milan (Italy)

When is the study starting and how long is it expected to run for?
January 2015 to December 2016

Who is funding the study?
The European Regional Development Fund

Who is the main contact?
1. Prof. Patrizia Riso (scientific)
patrizia.riso@unimi.it
2. Prof. Ornella Guardamagna (scientific)
ornella.guardamagna@unito.it

Contact information

Prof Patrizia Riso
Scientific

Università degli Studi di Milano, Via Celoria 2
Milano
20133
Italy

ORCID ID	0000-0002-9204-7257
Phone	+39 (0)250 316 726
Email	patrizia.riso@unimi.it

Prof Ornella Guardamagna
Scientific

Università degli Studi di Torino, Piazza Polonia 94
Torino
10126
Italy

Phone	+39 (0)113 135 243
Email	ornella.guardamagna@unito.it

Study information

Study design	8-week randomized controlled parallel single-blind dietary intervention study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Quality of life
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	Effect of hazelnut or polyunsaturated fat intake on oxidative stress related markers and lipid profile in children and adolescents with primary dyslipidemia
Study acronym	NO-OX Stress
Study objectives	Dyslipidemia is a major risk factor for cardiovascular disease development and it is closely associated with a decrease of antioxidant defense mechanisms. Nuts are rich sources of bioactives such as monounsaturated and polyunsaturated fatty acids, vitamins, phytosterols and polyphenols. We hypothesized that regular consumption of hazelnuts or other polyunsaturated sources (e.g. alpha-linolenic acid) could have a beneficial effect on dyslipidemia improving lipid profile and cell protection against oxidative DNA damage. Moreover, dietary interventions with polyunsaturated fats could also affect microbiota composition and inflammatory conditions eventually associated to dyslipidemia.
Ethics approval(s)	Ethics Committee of the City of Health and Science University Hospital of Turin, 22/01/2015, ref: EC:CS377
Health condition(s) or problem(s) studied	Familiar dyslipidemia
Intervention	The study is an 8-week randomized, controlled, parallel, single-blind dietary intervention study. Subjects receive dietary guidelines and individually randomized to the following three parallel groups of 20 subjects each: Group 1: Children consuming hazelnuts with skin as snack (between 15-30 g per day, based on body weight) Group 2: Children consuming hazelnuts without skin as snack (between 15-30 g per day, based on body weight) Group 3: Children who do not consume nuts (or children consuming other sources of unsaturated fats) At the beginning and at the end of the intervention (t= 8 weeks), blood and stool samples are collected and used to evaluate the oxidative stress related markers (e.g. DNA damage, oxidized LDL, PON-1 concentration, etc.), the serum lipid profile and erythrocyte membrane phospholipids composition. In addition, dietary and metabolic markers (e.g. microbiota composition, inflammatory related markers, etc.) are analysed.
Intervention type	Other
Primary outcome measure	Endogenous oxidized DNA bases (using enzyme formamidopyrimidine-DNA glycosylase) measured by Comet assay in peripheral blood mononuclear cells at baseline (t=0) and at the end of intervention (t=8 weeks)
Secondary outcome measures	1. Changes in serum lipid profile triglycerides, total cholesterol, high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol 2. Changes in erythrocyte phospholipids composition 3. Changes in anthropometric characteristics (age, weight, height, body mass index) 4. Changes in blood pressure (diastolic and systolic blood pressure) 5. Changes in oxidized LDL and paraoxonase 1 (PON-1) 6. Changes in markers of inflammation 7. Changes in microbiota composition All assessed at baseline and at the end of intervention (8 weeks)
Overall study start date	01/01/2015
Completion date	31/12/2016

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	5 Years
Upper age limit	17 Years
Sex	Both
Target number of participants	60 children/adolescents
Key inclusion criteria	1. Children aged 5-17 years affected by primary dyslipidemia (familiar hypercholesterolemia, familiar combined hyperlipidemia and undefined hypercholesterolemia), 2. Total cholesterol and/or triglycerides value higher than their age- and sex-specific 90th percentile 3. Body mass index (BMI) <95th percentile
Key exclusion criteria	1. Secondary dyslipidemias, overweight or obesity (BMI ≥ 85th and ≥ 95th percentile, age and sex matched, respectively) 2. Children under lipid-lowering treatment (including functional foods) from the 3 months before the beginning of the study 3. History of renal, endocrine, liver disorders, or chronic diseases (i.e., immunologic, neurologic, or oncohematologic disorders) 4. Smokers 5. Use of any drugs, supplements, specific prebiotics or probiotics or medications at least one month before the beginning of the experiment. 6. Subjects with specific aversion or allergies to food under study
Date of first enrolment	01/01/2015
Date of final enrolment	31/05/2016

Locations

Countries of recruitment

Italy

Study participating centres

University of Turin (Università degli Studi di Torino)

Department of Health, Sciences and Pediatric
Piazza Polonia 94
Torino
10126
Italy

University of Milan (Università degli Studi di Milano)

Department of Food, Environmental and Nutritional Sciences Division of Human Nutrition
Via Celoria 2
Milano
20133
Italy

Sponsor information

Regione Piemonte
Other

Piazza Castello 165
Torino
10123
Italy

Website	http://www.regione.piemonte.it/industria/

Funders

Funder type

Not defined

European Regional Development Fund
Government organisation / National government

Alternative name(s): Europski Fond za Regionalni Razvoj, Den Europæiske Fond for Regionaludvikling, Europees Fonds voor Regionale Ontwikkeling, Euroopa Regionaalarengu Fond, Fonds Européen de Développement Régional, Europäischer Fonds für regionale Entwicklung, Európai Regionális Fejlesztési Alap, Fondo Europeo di Sviluppo Regionale, Eiropas Reģionālās attīstības fonds, Europos Regionines Pletros Fondas, Europejski Fundusz Rozwoju Regionalnego, Fundo Europeu de Desenvolvimento Regional, Fondul European de Dezvoltare Regională, Európsky Fond Regionálneho Rozvoja, Fondo Europeo de Desarrollo Regional, Европейски фонд за регионално развитие, Evropský fond pro regionální rozvoj, Ευρωπαϊκό Ταμείο Περιφερειακής Ανάπτυξης, Il-Fond Ewropew għall-Iżvilupp Reġjonali, Evropski sklad za regionalni razvoj, Euroopan aluekehitysrahasto, Europeiska regionala utvecklingsfonden, ERDF, FEDER, EFRE, ЕФРР, EFRR, EFRU, ERFi, ΕΤΠΑ, FEDER, FESR, ERAF, ERPF, ERFA, L-FEŻR, EFRO, EFRR, FEDR, ESRR, EAKR, Eruf

Results and Publications

Intention to publish date	31/12/2017
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Other
Publication and dissemination plan
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/07/2018		Yes	No
Results article	results	01/08/2018		Yes	No

Editorial Notes

14/05/2018: Publication reference added.
14/06/2017: Publication reference added.