Clinical trial NCT04992936: Effect of an Extract From the Wine Industry on Blood Pressure (HYPERGRAPES)
Official title: Effect of an Alcohol-Free Extract From the Wine Industry on Blood Pressure in Individuals With High Blood Pressure and Grade 1 Hypertension. Randomized, Crossover, Controlled Double Blind Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Diseases
Hypertension
Keywords: Blood pressure
wine
by-products
Lead sponsor: Fundació Eurecat
Sponsor class: OTHER
Collaborators: name: University Rovira i Virgili
name: Grandes Vinos y Viñedos S.A.
First posted: 2021-08-05
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: By-products from the wine industry pose serious problems of management, both from an economic and environmental point of view. Although traditionally the use of by-products of the wine sector has been limited to the production of biogas and energy, or its use as animal feed or agricultural fertilizer, there is greater interest in the use of these by-products as a potential source of functional ingredients.

Cardiovascular diseases (CVD) are the main cause of mortality in Europe, with hypertension being one of the main CVD risk factors. It has been shown that lowering blood pressure through behavioral and pharmacological interventions significantly improves CVD. Currently, one of the most widely used pharmacological therapies to treat hypertension is based on the use of angiotensin converting enzyme (ACE) inhibitors such as Captopril or Enalapril. ACE plays a key role in arterial pressure regulation, catalyzing the production of angiotensin II, an octapeptide with potent vasoconstrictor activity. In addition, ACE catalyzes the inactivation of bradykinin, peptide with vasodilator activity. The evaluation of various potential by-products of the wine industry for the generation of functional ingredients showed that an extract from the wine industry presented beneficial effects on blood pressure in in vitro models as well as in vivo models using rats with hypertension.

Detailed description: The main objective of the study is to evaluate the effect of daily intake of an extract from the wine industry on the change in systolic blood pressure values in individuals with high blood pressure and grade 1 hypertension.

Secondary objectives are to evaluate the effects of an extract from the wine industry on:

* The change in diastolic blood pressure values.
* The change in body weight, body mass index (BMI) and waist circumference.
* The change in the circulating values of total cholesterol, LDL-c, HDL-c, triglycerides and ApoB.
* The change in the atherogenic index of plasma, which combines triglycerides and HDL-c values and which is considered a good indirect indicator of LDL-c particle size and subclinical atherosclerosis.
* Glucose metabolism and insulin resistance.
* The change in the inflammation values analyzed by the marker high sensitivity C-reactive protein.

Study Design: Randomized, crossover, placebo-controlled and double-blind nutritional intervention trial.

The number of subjects in the study will be 40. After the pre-screening visit, the participants will be randomly divided into two groups of 20 participants, according to start the study by taking the extract from the wine industry or placebo for 5 weeks. At the end of the week 5 of the study, when the first treatment is finished, there will be a washing period for 3 weeks and then the treatment will be changed for another 5 weeks: a total of 14 weeks.

The containers of the two treatments, the extract from the wine industry and the placebo, will present the same shape and appearance. The two products will present similar organoleptic characteristics of taste and color.

Each volunteer will make 5 visits, according to the crossover study design:

* a pre-selection visit (to check inclusion / exclusion criteria) (V0; week1) and, in case of meeting the inclusion criteria,
* two study visits during the consumption of the first product (extract from the wine industry or placebo), which will take place on the first day of study (V1; week 2) and after 5 weeks of treatment (V2; week 7).
* two study visits during the consumption of the second product (extract from the wine industry or placebo), which will take place after the three week washout period (V3; week 10) and after 5 weeks of treatment (V4; week 15).

In all visits except the V0 visit, participants must present themselves in fasting conditions of 8 hours to obtain blood. In addition, on V2 visits and V4 the participants will be asked the presence / absence of adverse effects that could be associated with the consumption of the study products.

Main variable: Systolic blood pressure levels.

Secondary variables:

* Diastolic blood pressure levels.
* Body weight.
* Height.
* Body mass index (BMI) (Kg/m2).
* Waist circumference.
* Conicity index.
* Waist circumference/Height ratio.
* Parameters in serum:
* Glucose.
* Insulin.
* Homeostatic Model Assessment for insulin resistance index (HOMA-IR).
* Total cholesterol.
* High density lipoproteins cholesterol (HDL-c).
* Low density lipoproteins cholesterol (LDL-c).
* Triglycerides (TG).
* Atherogenic indices:
* Total cholesterol/HDL-c
* LDL-c/HDL-c
* Plasma atherogenic index, calculated as the logarithm of the TG/HDL-c ratio.
* Apolipoprotein (apo) B.
* C-reactive protein.
* Faecal intestinal microbiota composition.
* Physical activity record.
* Record of potential adverse events.
* Frequency of consumption of supplements to avoid in the study.
* Completion of the intervention.

Eligibility criteria: Inclusion Criteria:

* Men and women over 18 years of age.
* Systolic blood pressure between 130- 159 mm Hg.
* Not under pharmacological treatment or have completed pharmacological treatment at least one month before the start of the study with anti-hypertensive and/or with lipid-lowering drugs. 2. Sign the informed consent.

Exclusion Criteria:

* BMI ≥ 35 kg/m\^2.
* Have a clinical history of chronic kidney disease, cardiovascular disease and/or cancer.
* Be a smoker or ex-smoker in the last 6 months before inclusion in the study.
* Present diabetes.
* Take supplements with polyphenol components or aimed to lipid or blood pressure control during their participation in the study.
* Take 2 or more Standard Beverage Units daily or 17 weekly for women, or take 4 or more Standard Beverage Units daily or 28 weekly for men.
* Present some chronic gastrointestinal disease.
* Present food intolerances and/or allergies related to the products of the study, such as hypersensitivity to maltodextrin and/or sulfites.
* Being pregnant or intending to become pregnant.
* Be in breastfeeding period.
* Participate in or have participated in a clinical trial with drugs 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: Change in systolic blood pressure
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
Secondary outcomes:
measure: Change in diastolic blood pressure
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Change in body weight
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Height
timeFrame: At week 1.
measure: Change in BMI
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in waist circumference
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in conicity index
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in waist circumference to height ratio
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in serum glucose levels
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in serum insulin levels
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in Homeostatic Model Assessment from Insulin Resistance Index (HOMA-IR)
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in serum total cholesterol levels.
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in serum HDL-c levels.
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in serum LDL-c levels.
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in serum Triglycerides levels
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in total cholesterol to HDL-c ratio
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in LDL-c to HDL-c ratio
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in Plasma atherogenic index
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in serum Apo B levels
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in serum C- Reactive protein levels
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Changes in intestinal microbiota composition
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Change in Physical activity
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
measure: Adverse events
timeFrame: Before (baseline) and after treatment period (5 weeks) for each of the two treatments (dry VLC and placebo).
Other outcomes:
Locations:
city: Reus
country: Spain
facility: Eurecat
Study officials:
affiliation: UTNS (Eurecat-Reus)
name: Josep M Del Bas, PhD
role: PRINCIPAL_INVESTIGATOR
References: