Clinical trial NCT05167747: Food Supplementation With Diuripres for Blood Pressure Modulation in Subjects With High-Normal Blood Pressure
Official title: Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Effect of a Combined Nutraceutical and Placebo on Blood Pressure Level, Vascular Health, and Metabolic Parameters in Subjects Affected by Normal-High Blood Pressure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: High-Normal Blood Pressure
Lead sponsor: University of Bologna
Sponsor class: OTHER
First posted: 2021-12-22
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, reaching the 31% of deaths in 2012. CVDs represent also the major cause of disability in developed countries and has been estimated that their growing burden could lead to a global increase in loss of disability-adjusted life years (DALY), from a loss of 85 million DALYs of 1990 to a loss of \~ 150 million DALYs in 2020, becoming a major cause of no psychic responsible for lost productivity.

Several risk factors contribute to the aetiology and development of CVD. These factors have been traditionally stratified into modifiable risk factors through the lifestyle changes or by taking a pharmacologic treatment (e.g. hypertension, smoking, diabetes mellitus, hypercholesterolemia) and not modifiable risk factors (age, male sex and family history). Essential hypertension is the most common modifiable risk factor in the general population, with a prevalence in Western Countries -including Italy- ranging between about 25-45%.

Given the large prevalence of the disease of the general population, hypertension is responsible for the vast majority of CVD in individuals with different CV risk profiles, despite the availability of effective and well tolerated antihypertensive therapies. In this regard, several reports have shown that hypertensive patients often present additional CV and metabolic risk factors, mostly hypercholesterolemia, hypertriglyceridemia, metabolic syndrome and diabetes, which further contribute to increase the individual risk of developing hypertension-related complications, including stroke, end-stage renal disease, congestive heart failure, and CVD death. The concomitant presence of hypertension and dyslipidaemia is also responsible for the objective difficulty in achieving the recommended therapeutic targets for BP and cholesterol levels in a setting of clinical practice.

Several pharmacological and non-pharmacological interventions have been proposed for ameliorating the relatively low rates of control of hypertension. Among these, an extensive use of nutrients and food supplements has been shown to provide favourable effects in the management and control of high-normal blood pressure (BP) (or pre-hypertension), that increases the risk of developing hypertension, cardiovascular diseases, and renal failure.

Detailed description: Among food supplements largely used in this field, Orthosiphon stamineus Benth leaf extract has been recognized for its well-known diuretic properties; extract of hawthorn (Crataegus curvisepala Lind.) has been shown to exert a renal-protective effect in high salt-induced hypertension and extract of hibiscus (Hibiscus sabdariffa L.) is well known for its antihypertensive and vasodilator effect in human. Moreover, supplementation with magnesium has been recently found to play a critical role in BP regulation, through directly stimulating prostacyclin and nitric oxide formation, modulating endothelium-dependent and endothelium-independent vasodilation, reducing vascular tone and reactivity, and preventing vascular injury via its antioxidant and anti-inflammatory functions.

The objective of this study is to evaluate the effect of dietary supplementation of a combined food supplement (NUT) containing magnesium, standardized extract of orthosiphon (Orthosiphon stamineus Benth), standardized extract of hawthorn (Crataegus curvisepala Lind.) and standardized extract of hibiscus (Hibiscus sabdariffa L.) compared to placebo, on blood pressure and other markers of vascular aging in subjects with high-normal blood pressure.

Eligibility criteria: Inclusion Criteria:

* Subjects agree to participate in the study and having dated and signed the informed consent form;
* Subjects who have the capability to communicate, to make themselves understood, and to comply with the study's requirements;
* Subjects with high-normal blood pressure (SBP= 130-139 mmHg and/or DBP= 85-89 mmHg);
* Subjects who, according to the SCORE charts, have a low or moderate cardiovascular risk (defined as a total cardiovascular risk \< 5%) and for whom, according to 2018 ESC/ESH guidelines, the intervention strategy does not require a pharmacological intervention.

Exclusion Criteria:

* Subjects already affected by cardiovascular diseases (secondary prevention) or with an estimated 10 years cardiovascular disease risk\> 5%;
* Obesity (Body mass index\>30 kg/m2);
* Type 1 or type 2 diabetes;
* Assumption of anti-hypertensive drugs or food supplements, or drugs potentially affecting blood pressure;
* Lipid-lowering treatment not stabilized since at least 2 months;
* Anticoagulants therapy;
* Known current thyroid, gastrointestinal or hepatobiliary diseases;
* Any medical or surgical condition that would limit the patient adhesion to the study protocol;
* Abuse of alcohol or drugs (current or previous);
* History of malignant neoplasia in the 5 years prior to enrolment in the study;
* History or clinical evidence of inflammatory disease such as severe arthritis, systemic lupus erythematosus or chronic inflammatory diseases or current therapy with immunosuppressive agents or long-term glucocorticoids;
* History or clinical evidence of any significant concomitant disease that could compromise the safety of the subject or the possibility of completing the study;
* Known previous intolerance to one component of the tested nutraceuticals;
* Women in fertile age not using consolidated contraceptive methods;
* Pregnancy and Breastfeeding.

Primary outcomes:
measure: Systolic blood pressure absolute reduction from baseline and between groups
timeFrame: 8 weeks
measure: Diastolic blood pressure absolute reduction from baseline and between groups
timeFrame: 8 weeks
Secondary outcomes:
measure: Systolic blood pressure absolute reduction from baseline and between groups
timeFrame: 4 weeks
measure: Diastolic blood pressure absolute reduction from baseline and between groups
timeFrame: 4 weeks
measure: Percent reduction from baseline and between groups in vascular reactivity
timeFrame: 4 weeks
measure: Percent reduction from baseline and between groups in vascular reactivity
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in body weight
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in body weight
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in body mass index
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in body mass index
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in waist circumference
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in waist circumference
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in hip circumference
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in hip circumference
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in waist/hip circumference ratio
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in waist/hip circumference ratio
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in the index of central obesity
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in the index of central obesity
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in the visceral adiposity index
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in the visceral adiposity index
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in fat and lean mass
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in fat and lean mass
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in renal function
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in renal function
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in serum lipids
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in lipids ratios
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in serum lipids
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in serum lipids ratios
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in high sensitivity C reactive protein
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in high sensitivity C reactive protein
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in serum uric acid concentrations
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in serum uric acid concentrations
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in fasting plasma glucose concentrations
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in fasting plasma glucose concentrations
timeFrame: 8 weeks
measure: Treatment acceptability
timeFrame: 4 weeks
measure: Treatment acceptability
timeFrame: 8 weeks
measure: Treatment tolerability
timeFrame: 4 weeks
measure: Treatment tolerability
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in liver transaminases and gamma glutamil transferase
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in liver transaminases and gamma glutamil transferase
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in augumentation pressure
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in augumentation index
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in augumentation pressure
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in augumentation index
timeFrame: 8 weeks
measure: Percent change from baseline and between groups in the estimated body water content
timeFrame: 4 weeks
measure: Percent change from baseline and between groups in the estimated body water content
timeFrame: 8 weeks
measure: Absolute change from baseline and between groups in estimated risk of cardiovascular disease
timeFrame: 4 weeks
measure: Absolute change from baseline and between groups in estimated risk of cardiovascular disease
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: S. Orsola-Malpighi University Hospital
Study officials:
affiliation: S. Orsola-Malpighi University Hospital
name: Arrigo F. Cicero, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fogacci F, Degli Esposti D, Di Micoli A, Fiorini G, Veronesi M, Borghi C, Cicero AFG. Effect of dietary supplementation with Diuripres(R) on blood pressure, vascular health, and metabolic parameters in individuals with high-normal blood pressure or stage I hypertension: The CONDOR randomized clinical study. Phytother Res. 2023 Oct;37(10):4851-4861. doi: 10.1002/ptr.7951. Epub 2023 Jul 14.