Nitrate and Brain Insulin-Sensitivity (NO-BRAINS)

• ClinicalTrials.gov Identifier: NCT04700241
• Recruitment Status: Completed
• First Posted: January 7, 2021
• Last Update Posted: June 9, 2021
• Sponsor: Maastricht University Medical Center
• Information provided by (Responsible Party): Maastricht University Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Nitrate; Brain Insulin-sensitivity; Vascular Function	Dietary Supplement: Potassium nitrate; Dietary Supplement: Placebo	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Acute Effects of Inorganic Nitrate on Brain Insulin-sensitivity in Abdominally Obese Men
• Actual Study Start Date: January 21, 2021
• Actual Primary Completion Date: May 5, 2021
• Actual Study Completion Date: May 5, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Potassium nitrate; During this experimental day, men will receive 10 mmol of potassium nitrate	Dietary Supplement: Potassium nitrate; Acute intervention (5.5 hours)
Placebo Comparator: Placebo; During this experimental day, men will receive an isomolar dose of potassium chloride	Dietary Supplement: Placebo; Acute intervention (5.5 hours)

Outcome Measures

Primary Outcome Measures :

1. Brain insulin sensitivity [ Time Frame: 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 :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Netherlands

Maastricht University Medical Center

Maastricht, Limburg, Netherlands, 6229 ER

Sponsors and Collaborators

Maastricht University Medical Center

Investigators

• Principal Investigator: Peter J. Joris, Dr; Maastricht University
• Principal Investigator: Ronald P.M. Mensink, Dr; Maastricht University

More Information

• Responsible Party: Maastricht University Medical Center
• ClinicalTrials.gov Identifier: NCT04700241
• Other Study ID Numbers: METC 20-0.78
• First Posted: January 7, 2021
• Last Update Posted: June 9, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Insulin Resistance; Hypersensitivity; Immune System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases