Clinical trial NCT03679195: Effect of Polyphenols Combined to L-citrulline on Ambulatory Blood Pressure
Official title: Impact of a Supplementation With Grape Seed and Cranberry Extracts on Ambulatory Blood Pressure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Keywords: 24h ambulatory blood pressure vascular function inflammation
Lead sponsor: Laval University
Sponsor class: OTHER
Collaborators: name: Atrium Innovations
First posted: 2018-09-20
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The general objective of this project is to investigate the chronic effect of consuming supplements combining polyphenols from cranberry and grape seed extracts and L-citrulline (Nitric Oxide Ultra capsules, Pure Encapsulations, Sudbury, MA) on 24-hour ambulatory blood pressure, markers of vascular function and plasma biomarkers of inflammation in adults with pre-hypertension.

The study will be undertaken according to a double-blind, parallel, randomized, placebo controlled design and will be conducted at the Institute of Nutrition and Functional Foods (INAF) of Laval University. The study will involve a total of 73 adult men and women. Included subjects will be randomly assigned to a 6-week period of supplementation with Nitric Oxide (NO) Ultra capsules or placebo (cellulose capsules). The outcomes are the chronic changes after supplementation with NO Ultra capsules compared with the placebo in: 24-hour ambulatory diastolic and systolic blood pressure, levels of blood lipids and inflammation markers, levels of blood and cutaneous markers of vascular function.

Detailed description: There is now evidence that blood pressure, vascular function and inflammation are intimately associated with cardiovascular disease. It is also clear that several dietary components including polyphenols and L-citrulline can modify blood pressure control. However, based on the studies available so far, it is difficult to draw firm conclusion on the potential impact of a dietary supplement combining polyphenols and L-citrulline on ambulatory blood pressure in pre-hypertensive subjects at risk to develop hypertension and cardiovascular disease. To the best of our knowledge, no study has yet investigated the chronic impact of combined polyphenols and L-citrulline on both ambulatory blood pressure and vascular function/inflammation.

The present supplementation based on polyphenols and L-citrulline may represent for pre-hypertensive subjects a new dietary modality to manage blood pressure as part of healthy eating.

The study will be undertaken according to a double-blind, parallel, randomized, placebo controlled design and will be conducted at the Institute of Nutrition and Functional Foods (INAF) of Laval University. A total of 73 adult men and women will be recruited based primarily on blood pressure criteria in the Quebec City metropolitan area. Participants will be randomly assigned to a 6-week period of supplementation with Nitric Oxide Ultra capsules or placebo (cellulose capsules). Participants in the NO Ultra group will be supplemented with 764 mg/day of cranberry and grape seed extracts (containing polyphenols) and 2 g/day of L-citrulline. Participants will have to take daily 2 capsules (NO Ultra or placebo) between breakfast and lunch and 2 capsules (NO Ultra or placebo) between lunch and dinner. Specifically, capsules will be taken with water and no foods, and at least one-hour apart meals. Office and 24-hour ambulatory blood pressure, blood lipids, cutaneous and plasma markers of vascular function, plasma inflammation biomarkers and anthropometric characteristics will be measured at the beginning and at the end of the study.

Eligibility criteria: Inclusion Criteria:

* Men and women aged between 18-75 years
* For women with child-bearing potential, acceptable effective contraceptive methods are: total abstinence, hormonal birth control methods (oral, injectable, transdermal or intra-vaginal), intrauterine devices, confirmed successful vasectomy of partner
* Stable weight for at least three 3 months (±5lbs)
* Mean daytime SBP between 125 and 134.9 mmHg and DBP \< 85 mmHg
* Otherwise healthy individuals

Exclusion Criteria:

* Women during a peri-menopausal period
* Pregnant/breastfeeding women
* Mean daytime SBP \<125 or \>134.9 mmHg or DBP ≥85 mmHg
* History of cardiovascular disease, type 2 diabetes, monogenic dyslipidemia or endocrine disorders
* Use of anticoagulants or thrombocyte aggregation inhibitors, chemotherapeutic agents, anti-inflammatory drugs, medication for blood lipids, diabetes, hypertension, erectile dysfunction or auto-immune diseases
* Any clinical signs or laboratory evidence for inflammatory, gastrointestinal, endocrine, renal, pulmonary, neurological, cardiovascular, metabolic, haematological problem or cancer
* Kidney stones
* Excess alcohol consumption (\> 14 consumptions/week) or drug consumption
* Hypersensitivity/allergy to one of the ingredients (including non-medicinal ingredients) in NO Ultra supplement/placebo
* Use of additional cranberry/grape seed extract or citrulline products

Primary outcomes:
measure: 24-hour ambulatory diastolic blood pressure
timeFrame: 6 weeks (end-point value)
Secondary outcomes:
measure: 24-hour ambulatory systolic blood pressure
timeFrame: 6 weeks (end-point value)
measure: Blood Lipids
timeFrame: 6 weeks (end-point value)
measure: Vascular function
timeFrame: 6 weeks (end-point value)
measure: Inflammation biomarkers
timeFrame: 6 weeks (end-point value)
Other outcomes:
Locations:
city: Québec
country: Canada
facility: Institute of Nutrition and Funtional Foods
Study officials:
affiliation: Laval University
name: Benoît Lamarche, PhD
role: PRINCIPAL_INVESTIGATOR
References: