Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03870984 |
| Other study ID # |
VRINoci |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 19, 2019 |
| Est. completion date |
May 18, 2022 |
Study information
| Verified date |
May 2022 |
| Source |
Universita di Verona |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Obesity is a problem of ever-growing importance, especially in industrialized countries, both
in adults and in the pediatric population. Children and obese adolescents, like adults, have
an increased risk, compared with normal-weight peers, to develop metabolic syndrome and
atherosclerotic disease, pathophysiological basis of cardiovascular events. Alteration of the
elastic properties of the arteries has been described previously in obese children and
adolescents and is considered an initial marker of atherosclerotic vascular damage. The
determination of the indices of arterial stiffness (PWV, Pulse Wave Velocity; AI,
Augmentation Index, SI, Stiffness Index) is possible through techniques currently used for
the determination of vascular function even in children.
Nuts and hazelnuts are rich in potentially beneficial substances including unsaturated fatty
acids, especially omega-6 (present in both) and omega-3 (present only in nuts), Several
clinical trials have already shown in adults a potential beneficial effect of the addition of
different types of nuts (walnuts, hazelnuts, cashews, pistachios, etc.) on the
characteristics of the metabolic syndrome also through their possible antioxidant effect and
vasoactive. In children, some epidemiological studies have associated with a higher
consumption of nuts reduced risk of hypertension, dyslipidemia, obesity and fasting glucose.
The study will be conducted with a randomized design with two arms in parallel with blinded
operator. The main objective of this study is to assess the efficacy of 15 grams of nuts and
15 grams of nuts a day in addition to a low calorie diet on the content of erythrocyte
membranes of alpha-linolenic acid three months after the beginning of the trial in a group of
obese children. Secondary objectives are to evaluate the efficacy of walnuts and hazelnuts in
improving the systolic and/or diastolic blood pressure values, lipid profile, glucose and
fasting insulin, vascular function.
Description:
Obesity is a problem of ever-growing importance, especially in industrialized countries,
widespread both in adults and in the pediatric population.
Children and obese adolescents, like adults, have an increased risk, compared with
normal-weight peers, to develop high blood pressure, insulin resistance, diabetes,
hyperlipidemia, fatty liver disease and the resulting long-term complications. This cluster
of metabolic and hemodynamic risk factors, which is known as metabolic syndrome, greatly
increases the risk of cardiovascular events in adults. Cardiovascular disease is the leading
cause of mortality and morbidity in developed countries and are becoming even in developing
countries. Atherosclerotic disease is the pathophysiological basis of cardiovascular events.
Atherosclerosis is a multifactorial disease whose early stages of subclinical damage are
documented much earlier in cardiovascular events with non-invasive tests. The determination
of the indices of arterial stiffness (PWV, Pulse Wave Velocity; AI, Augmentation Index, SI,
Stiffness Index) is possible through techniques currently used for the determination of
vascular function even in children. The alteration of the elastic properties of the arteries
has been described previously in obese children and adolescents and is considered initial
marker atherosclerotic vascular damage. Fats particularly saturated fats, without adequate
intake of polyunsaturated fat, may facilitate the development of obesity.
The consumption of some specific foods including dried fruit (in a broad sense including
walnuts, hazelnuts, almonds, cashews, etc.) within a reduced calorie diet is considered to be
a promising approach in the prevention and care of the different components of the metabolic
syndrome. The nuts and hazelnuts are rich in potentially beneficial substances including
unsaturated fatty acids, especially omega-6 (present in both) and omega-3 (present only in
nuts), L-arginine, fiber, minerals, vitamin E, fitosetrols and polyphenols.
Several clinical trials have already shown in adults a potential beneficial effect of the
addition of different types of nuts (walnuts, hazelnuts, cashews, pistachios, etc.) on the
characteristics of the metabolic syndrome also through their possible antioxidant and
vasoactive effect .
In children, some epidemiological studies have associated a higher consumption of nuts with
reduced risk of hypertension, dyslipidemia, obesity and fasting glucose alteration.
Our group conducted a study in obese children observing an inverse relationship between
omega-6 polyunsaturated fatty acids, contained in large amounts in walnuts, and certain
features of metabolic syndrome, such as waist circumference, triglycerides, fasting insulin,
systolic blood pressure of 24-hours, suggesting a possible beneficial effect. The project was
financed by health ministry and included also the present Protocol ("Obesity, hypertension
and subclinical vascular damage in children: the role of dietary factors and lipid mediators.
An epidemiological and translational study. "Project Code: GR-2011-02349630).
From arachidonic acid, the main omega-6 type polyunsaturated fatty acids (PUFA), certain
metabolites are produced via cytochrome P450 which have vasoactive and natriuretic effect:
20-Hydroxyeicosatetraenoic acid (20-HETE), the epoxyeicosatrienoic acids (EETs) and
dihydroxyeicosatrienoic acids (DHETs). From numerous studies in animal models and some human
studies, it is known that these metabolites via cytochrome P450 may be involved both in the
homeostasis of blood pressure pressure and in the development of hypertension. In particular,
plasmatic 20-HETE has a vasoconstrictor effect while EETs are vasodilators; both exert renal
natriuretic effect. Our study intends to verify if in a group of obese children, a
low-calorie diet that contains a portion of walnuts and hazelnuts, can change the content of
polyunsaturated fatty acids in erythrocyte membranes, particularly alpha-linolenic acid. This
could result in possible beneficial effects on the characteristics of the metabolic syndrome
in obese children, like an improvement of waist circumference, blood pressure, HDL
cholesterol, triglycerides and blood sugar. Our study also intends to acquire information on
the effect of the addition of walnuts and hazelnuts and the metabolites of polyunsaturated
fatty acids omega-3 and omega-6 metabolized by cytochrome P450 that derives from these nuts
in change vessel elasticity.
2. STUDY DESIGN The study will be conducted with a randomized design (two arms in parallel
with blinded operator). Doctors in charge of vascular measurements and laboratory technicians
will not know which of the two groups analyzed will only have taken the low-calorie diet and
who will have assumed the low-calorie diet with walnuts and hazelnuts.
3. PURPOSE OF THE STUDY
The main objective of this study is to assess the efficacy of 15 grams of nuts and 15 grams
of nuts a day in addition to a low calorie diet, in modifying the content of of
alpha-linolenic acid in erythrocyte membranes evalutated three months after the beginning of
the assumption in a group of obese children.
Secondary objectives are:
To evaluate the efficacy of walnuts and hazelnuts in improving in obese children:
- the systolic and/or diastolic blood pressure values;
- metabolic disorders (in particular of the lipid profile: LDL, HDL, triglycerides, and
glucose: glucose and fasting insulin);
- vascular function measured by tonometry (PWV and PWA), and ultrasonography (carotid
distensibility).
- the modifications of the profile of eicosanoids via CYP450 in plasma and urine
To evaluate:
- the relationship between intake of nuts and hazelnuts, fatty acid profile of erythrocyte
membranes and eicosanoids via CYP450, the components of the metabolic syndrome including the
blood pressure and vascular elasticity.
