Nitrate and Brain Insulin-Sensitivity

Not Applicable

Completed

• Conditions: Vascular Function; Brain Insulin-sensitivity; Nitrate
• Interventions: Dietary Supplement: Placebo; Dietary Supplement: Potassium nitrate

• Registration Number: NCT04700241
• Lead Sponsor: Maastricht University Medical Center

Brief Summary

Disturbances in brain insulin-sensitivity are not only observed in abdominal obesity and type 2 diabetes mellitus (T2D), but also during brain aging and in dementia. Inorganic nitrate may improve brain insulin-sensitivity, which can be quantified by measuring the gray-matter cerebral blood flow (CBF) response to intranasally administered insulin, through beneficial effects on brain vascular function. Therefore, we now hypothesize that inorganic nitrate, which can be found in several vegetables such as beetroot, improves brain insulin-sensitivity, as assessed by the gray-matter CBF response to intranasally administered insulin, in abdominally obese men.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-01-06
• Study First Submitted QC: 2021-01-06
• Study First Posted: 2021-01-07
• Study Start: 2021-01-21
• Status Verified: 2021-04
• Primary Completion: 2021-05-05
• Study Completion: 2021-05-05
• Last Update Submitted: 2021-06-08
• Last Update Posted: 2021-06-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 18

Inclusion Criteria

• Men;
• Aged between 18 - 60 years;
• Waist circumference > 102 cm (abdominally obese);
• Fasting plasma glucose ≤ 7.0 mmol/L;
• Fasting serum total cholesterol ≤ 8.0 mmol/L;
• Systolic blood pressure < 160 mmHg and diastolic blood pressure < 100 mmHg;
• 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;
• Willingness not to use antibacterial mouth wash or toothpaste, chewing-gum and tongue-scraping a week before the study;
• No difficult venipuncture as evidenced during the screening visit.

Exclusion Criteria

• Women;
• Left-handedness;
• Current smoker, or smoking cessation < 12 months;
• Diabetic patients;
• Familial hypercholesterolemia;
• Abuse of drugs;
• More than 3 alcoholic consumptions per day;
• Use of products or dietary supplements known to interfere with the main outcomes as judged by the principal investigators;
• Use medication to treat blood pressure, lipid or glucose metabolism;
• Pharmacological treatment advised based on the Dutch general practitioners' association (NHG) for cardiovascular risk management;
• 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;
• Specific contra-indications for MRI imaging, including pacemakers, surgical clips/material in body, metal splinters in eye, claustrophobia, or tattoos in the facial area, such as permanent make-up.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	During this experimental day, men will receive an isomolar dose of potassium chloride
Potassium nitrate	Potassium nitrate	During this experimental day, men will receive 10 mmol of potassium nitrate

Primary Outcome Measures

Name	Time	Method
Brain insulin sensitivity	Change from placebo intervention at 2 hours after supplement intake	MRI arterial spin labeling, cerebral blood flow measurements before and after a nasal insulin spray

Secondary Outcome Measures

Name	Time	Method
Postprandial metabolism (1)	During the 5.5 hours following supplement intake	Serum lipid metabolism
Cold pressure test	Change from placebo at 4 hours after supplement intake	Carotid artery response to cold pressure test
Cardiometabolic risk markers (1)	Change from placebo at 4 hours after supplement intake	Plasma markers for low-grade systemic inflammation (CRP)
Cardiometabolic risk markers (3)	Change from placebo at 4 hours after supplement intake	Office blood pressure
Cardiometabolic risk markers (4)	During the 5.5 hours following supplement intake	Plasma brain derived neurotrophic factor (BDNF)
Postprandial metabolism (2)	During the 5.5 hours following supplement intake	Plasma glucose metabolism
Brain vascular function	Change from placebo intervention at 2 hours after supplement intake	MRI arterial spin labeling, cerebral blood flow measurements
Vascular function markers	Change from fasting at 4 hours after supplement intake	Flow-mediated vasodilation (FMD) of the brachial and femoral artery
Cardiometabolic risk markers (2)	Change from placebo at 4 hours after supplement intake	Plasma marker for endothelial dysfunction (NOx)

Trial Locations

Locations (1)

Maastricht University Medical Center; 🇳🇱 Maastricht, Limburg, Netherlands