Clinical trial NCT04700241: Nitrate and Brain Insulin-Sensitivity
Official title: Acute Effects of Inorganic Nitrate on Brain Insulin-sensitivity in Abdominally Obese Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nitrate
Brain Insulin-sensitivity
Vascular Function
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2021-01-07
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.


Eligibility 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.

Primary outcomes:
measure: Brain insulin sensitivity
timeFrame: Change from placebo intervention at 2 hours after supplement intake
Secondary outcomes:
measure: Brain vascular function
timeFrame: Change from placebo intervention at 2 hours after supplement intake
measure: Vascular function markers
timeFrame: Change from fasting at 4 hours after supplement intake
measure: Cold pressure test
timeFrame: Change from placebo at 4 hours after supplement intake
measure: Cardiometabolic risk markers (1)
timeFrame: Change from placebo at 4 hours after supplement intake
measure: Cardiometabolic risk markers (2)
timeFrame: Change from placebo at 4 hours after supplement intake
measure: Cardiometabolic risk markers (3)
timeFrame: Change from placebo at 4 hours after supplement intake
measure: Cardiometabolic risk markers (4)
timeFrame: During the 5.5 hours following supplement intake
measure: Postprandial metabolism (1)
timeFrame: During the 5.5 hours following supplement intake
measure: Postprandial metabolism (2)
timeFrame: During the 5.5 hours following supplement intake
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
Study officials:
affiliation: Maastricht University
name: Peter J. Joris, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Maastricht University
name: Ronald P.M. Mensink, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kleinloog JPD, Mensink RP, Smeets ETHC, Ivanov D, Joris PJ. Acute inorganic nitrate intake increases regional insulin action in the brain: Results of a double-blind, randomized, controlled cross-over trial with abdominally obese men. Neuroimage Clin. 2022;35:103115. doi: 10.1016/j.nicl.2022.103115. Epub 2022 Jul 14.