HypertensionNCT03679195
Effect of Polyphenols Combined to L-citrulline on Ambulatory Blood Pressure
A study testing NO Ultra in people with Hypertension, run by Laval University at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension
- What is being tested?
- NO Ultra
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 73 participants
- Where
- 1 siteCanada
- Study dates
- 12 Sep 2018to 15 Jan 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of a Supplementation With Grape Seed and Cranberry Extracts on Ambulatory Blood Pressure
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.
Read the 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.
- Conditions
- Hypertension
- Being tested
- NO Ultra, Placebo
- Keywords
- 24h ambulatory blood pressure vascular function inflammation
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NO UltraDietary supplement
6-week supplementation period 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 NO Ultra capsules (containing 382 mg cranberry and grape seed extracts / 1 g L-citrulline) between breakfast and lunch and 2 other NO Ultra capsules between lunch and dinner.
PlaceboDietary supplement
Also called Cellulose capsules
6-week supplementation period with placebo capsules (the active ingredients will be replaced by cellulose)
Participants will have to take 2 capsules of cellulose between breakfast and lunch and 2 capsules between lunch and dinner to match the number of capsules ingested daily by the NO Ultra group.
| Study group | Role | What they receive |
|---|---|---|
| NO Ultra (Nitric Oxid Ultra Capsules) | Experimental | 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 NO Ultra capsules (containing 382 mg cranberry and grape seed extracts / 1 g L-citrulline) between breakfast and lunch and 2 other NO Ultra capsules between lunch and dinner. Receives: Dietary Supplement: NO Ultra |
| Placebo (Cellulose Capsules) | Placebo comparator | Participants will consume cellulose capsules that are similar in shape and size to the NO ultra product, i.e. 2 capsules between breakfast and lunch and 2 other capsules between lunch and dinner. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-hour ambulatory diastolic blood pressure
Comparison of the change from baseline in 24-hr ambulatory diastolic blood pressure at 6-wk between the NO Ultra group and the placebo group.
Measured: 6 weeks (end-point value)
Secondary outcomes (4)
24-hour ambulatory systolic blood pressure
Comparison of the change from baseline in 24-hr ambulatory systolic blood pressure at 6-wk between the NO Ultra group and the placebo group.
Measured: 6 weeks (end-point value)
Blood Lipids
Comparison of the change from baseline in serum total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, non HDL cholesterol, TG, and apolipoprotein B levels as well as in the total cholesterol/HDL cholesterol ratio at 6-wk between the NO Ultra group and the placebo group.
The concentration of the above lipids will be assessed on a Roche/Hitachi Modular analytical system (Roche Diagnostics) according to the manufacturer's specifications and using proprietary reagents. Serum LDL cholesterol concentrations will be calculated using the Friedewald equation.
Measured: 6 weeks (end-point value)
Vascular function
Comparison of the change from baseline in serum markers of vascular function including concentrations of angiotensin-converting enzyme (ACE), angiotensin-II (A-II), aldosterone (ALDOS), soluble forms of intercellular adhesion molecules (sICAM-1), soluble form of vascular cell adhesion molecule-1 (sVCAM-1) and soluble form of E-selectin (sE-selectin), as well as in the skin concentration of advanced glycation end products (AGEs) at 6-wk between the NO Ultra group and the placebo group.
Plasma concentrations of ACE, A-II, aldosterone ALDOS, sICAM-1, sVCAM-1 and sE-selectin will be determined using commercial ELISA kits for the human form of these markers. Measurement of the skin concentration of AGEs iwill be performed using a sensitive optical measurement device called AGE scanner (DiagnOptics, Groningen, The Netherlands).
Measured: 6 weeks (end-point value)
Inflammation biomarkers
Comparison of the change from baseline in serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), IL-18 and tumor necrosis factor alpha (TNF-a) at 6-wk between the NO Ultra group and the placebo group.
Serum CRP concentrations will be measured using of the Behring Latex-Enhanced highly sensitive assay on the Behring Nephelometer BN-100 system. Serum IL-6, IL-18, and TNF-alpha concentrations will be determined using commercial ELISA kits for the human form of these cytokines.
Measured: 6 weeks (end-point value)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2018
- Study start12 Sep 2018
- Primary completion12 Jun 2019
- Study completion15 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Laval UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laval University
- Sponsor type
- University, hospital or other
- Collaborators
- Atrium Innovations
- Responsible party
- Principal investigator, Benoit Lamarche, Laval University
- Investigators
- Benoît Lamarche, PhD, Principal investigator, Laval University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03679195
- Sponsor's protocol ID
- INAF_NO_2017-207
- Status last verified
- Feb 2020
- First submitted
- 14 Sep 2018
- Last updated
- 16 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of a Supplementation With Grape Seed and Cranberry Extracts on Ambulatory Blood Pressure
- ClinicalTrials.gov ID
- NCT03679195
- Acronym / sponsor ID
- INAF_NO_2017-207
- Conditions
- Hypertension
- Keywords
- 24h ambulatory blood pressure vascular function inflammation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- Laval UniversityUniversity, hospital or other
- Collaborators
- Atrium Innovations
- Study start
- 12 Sep 2018 (actual)
- Primary completion
- 12 Jun 2019 (actual)
- Study completion
- 15 Jan 2021 (actual)
- First posted
- 20 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NO Ultra (Nitric Oxid Ultra Capsules) | Experimental | Dietary Supplement: NO Ultra764 mg/day of cranberry and grape seed extracts (containing polyphenols) and 2 g/day of L-citrulline. Participants will have to take daily 2 NO Ultra capsules (containing 382 mg cranberry and grape seed extracts / 1 g L-citrulline) between breakfast and lunch and 2 other NO Ultra capsules between lunch and dinner. |
| Placebo (Cellulose Capsules) | Placebo comparator | Dietary Supplement: PlaceboParticipants will consume cellulose capsules that are similar in shape and size to the NO ultra product, i.e. 2 capsules between breakfast and lunch and 2 other capsules between lunch and dinner. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NO Ultra6-week supplementation period 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 NO Ultra capsules (containing 382 mg cranberry and grape seed extracts / 1 g L-citrulline) between breakfast and lunch and 2 other NO Ultra capsules between lunch and dinner. | Dietary supplement | NO Ultra (Nitric Oxid Ultra Capsules) |
| PlaceboAlso: Cellulose capsules6-week supplementation period with placebo capsules (the active ingredients will be replaced by cellulose) Participants will have to take 2 capsules of cellulose between breakfast and lunch and 2 capsules between lunch and dinner to match the number of capsules ingested daily by the NO Ultra group. | Dietary supplement | Placebo (Cellulose Capsules) |
Primary outcome
24-hour ambulatory diastolic blood pressure
Time frame: 6 weeks (end-point value)
Comparison of the change from baseline in 24-hr ambulatory diastolic blood pressure at 6-wk between the NO Ultra group and the placebo group.
4 secondary outcomes
24-hour ambulatory systolic blood pressure
Time frame: 6 weeks (end-point value)
Blood Lipids
Time frame: 6 weeks (end-point value)
Vascular function
Time frame: 6 weeks (end-point value)
Inflammation biomarkers
Time frame: 6 weeks (end-point value)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benoît Lamarche, PhD principal investigator
Laval University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing NO Ultra in people with Hypertension, run by Laval University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24-hour ambulatory diastolic blood pressure (time frame: 6 weeks (end-point value)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2022; AzTrials last refreshed its copy on 8 Nov 2026.