Nutritional Supplements and Nitric Oxide Bioactivity

• Sponsor: Maastricht University Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT03625596
• Collaborator: Nutricia Research (Industry)
• Enrollment: 20
• Location: 1
• Arms: 5
• Actual Duration (Months): 13
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

Obese people have a disturbed postprandial metabolism and thereby a decreased postprandial vascular function. Nitric oxide plays an important role in the postprandial vascular function. Multiple studies already focused on various nutritional compounds to improve the postprandial vascular function by increasing the nitric oxide bioactivity. However, the vast majority of the trials has been performed with relatively high doses of the individual components, which are problematic to convert into daily food measures, thereby preventing translation of these findings. Well-designed trails studying the effect of feasible amounts of nutritional supplements on the bioactivity of nitric oxide and vascular function are missing.

Condition or Disease	Intervention/Treatment	Phase
Nitric Oxide; Vascular Function; L-Arginine; Nitrate / Nitrite; Postprandial Metabolism	Dietary Supplement: L-Arginine; Dietary Supplement: Nitrate / Nitrite; Dietary Supplement: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Crossover assignmentCrossover assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: The Effects of Nutritional Supplements on Postprandial Nitric Oxide Bioactivity in Abdominally Obese Men
• Actual Study Start Date: Dec 1, 2018
• Actual Primary Completion Date: Dec 31, 2019
• Actual Study Completion Date: Dec 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: High L-arginine During this experimental day, men will receive a high-fat shake with a high dose of L-arginine.	Dietary Supplement: L-Arginine; Acute intervention (3 hours)
Experimental: Medium L-arginine + Nitrate / Nitrite During this experimental day, men will receive a high-fat shake with a medium dose of L-arginine enriched with nitrate and nitrite.	Dietary Supplement: L-Arginine; Acute intervention (3 hours); Dietary Supplement: Nitrate / Nitrite; Acute intervention (3 hours)
Experimental: Low L-arginine + Nitrate / Nitrite During this experimental day, men will receive a high-fat shake with a low dose of L-arginine enriched with nitrate and nitrite.	Dietary Supplement: L-Arginine; Acute intervention (3 hours); Dietary Supplement: Nitrate / Nitrite; Acute intervention (3 hours)
Experimental: Nitrate / Nitrite During this experimental day, men will receive a high-fat shake with nitrate and nitrite.	Dietary Supplement: Nitrate / Nitrite; Acute intervention (3 hours)
Placebo Comparator: Placebo During this experimental day, men will receive a high-fat shake without supplement.	Dietary Supplement: Placebo; Acute intervention (3 hours)

Outcome Measures

Primary Outcome Measures

1. Nitric oxide bioavailability [Change from baseline at 2 hours after supplement intake]

   Flow-mediated vasodilation (FMD) of the brachial artery

Secondary Outcome Measures

1. Nitric oxide bioavailability [During 3 hours following supplement intake]

   Plasma cyclic guanosine monophosphate (cGMP)

2. Vascular function markers [Change from baseline at 2 hours after supplement intake]

   Retinal microvascular calibers

3. Cardiometabolic risk markers (1) [Change from baseline at 2 hours after supplement intake]

   Plasma markers for low-grade systemic inflammation (CRP)

4. Cardiometabolic risk markers (2) [Change from baseline at 2 hours after supplement intake]

   Plasma markers for endothelial dysfunction (NOx)

5. Cardiometabolic risk markers (3) [Change from baseline at 2 hours after supplement intake]

   Office blood pressure

6. Postprandial metabolism (1) [During 3 hours following supplement intake]

   Serum lipid metabolism

7. Postprandial metabolism (2) [During 3 hours following supplement intake]

   Plasma glucose metabolism

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 70 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Men

• Aged between 40-70 years

• Waist circumference ≥ 102

• Fasting plasma glucose < 7.0 mmol/L

• Fasting serum total cholesterol < 8.0 mmol/L

• Stable body weight (weight gain or loss < 3 kg in the past three months)

• Willingness to give up being a blood donor from 8 weeks before the start of the study, during the study and for 4 weeks after completion of the study

• No difficult venipuncture as evidenced during the screening visit

• No current smoker

• No diabetic patients

• No familial hypercholesterolemia

• No abuse of drugs

• No more than 3 alcoholic consumptions per day

• No use of medication known to treat blood pressure, lipid or glucose metabolism

• No use of an investigational product within another biomedical intervention trial within the previous 1-month

• No severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis

• No active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident

• Willingness to give up the use of antibacterial mouth wash or antibacterial toothpaste, chewing-gum and tongue- scraping on the morning of each experimental test day

Exclusion Criteria:

• Women

• Fasting plasma glucose ≥ 7.0 mmol/L

• Fasting serum total cholesterol ≥ 8.0 mmol/L

• Current smoker, or smoking cessation <12 months

• Diabetic patients

• Familial hypercholesterolemia

• Abuse of drugs

• More than 3 alcoholic consumptions per day

• Unstable body weight (weight gain or loss > 3 kg in the past three months)

• Use medication known to treat blood pressure, lipid or glucose metabolism

• Use of an investigational product within another biomedical intervention trial within the previous 1-month

• Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis

• Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident

• Not willing to give up being a blood donor from 8 weeks before the start of the study, during the study or for 4 weeks after completion of the study

• Not or difficult to venipuncture as evidenced during the screening visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maastricht University Medical Center	Maastricht	Limburg	Netherlands	6229 ER

Sponsors and Collaborators

• Maastricht University Medical Center
• Nutricia Research

Investigators

• Principal Investigator: Peter J Joris, PhD, Maastricht University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Maastricht University Medical Center
• ClinicalTrials.gov Identifier: NCT03625596
• Other Study ID Numbers: METC 18-3-010
• First Posted: Aug 10, 2018
• Last Update Posted: Feb 20, 2020
• Last Verified: Feb 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Study Results

No Results Posted as of Feb 20, 2020