Nitrate and Brain Insulin-Sensitivity

Vascular Function Clinical Trial

— NO-BRAINS  

Official title:

Acute Effects of Inorganic Nitrate on Brain Insulin-sensitivity in Abdominally Obese Men

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04700241
• Other study ID #: METC 20-0.78
• Status: Completed
• Phase: N/A
• Start date: January 21, 2021
• Est. completion date: May 5, 2021

Study information

• Verified date: April 2021
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: May 5, 2021
• Est. primary completion date: May 5, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Brain Insulin-sensitivity
• Hypersensitivity
• Insulin Resistance
• Nitrate
• Vascular Function

Intervention

Dietary Supplement:
• Potassium nitrate
Acute intervention (5.5 hours)
• Placebo
Acute intervention (5.5 hours)

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center	Maastricht	Limburg

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

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