Nitrate and Brain Insulin-Sensitivity

NCT04700241 | Completed DMC

• 1 other identifier: METC 20-0.78
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Nitrate; Brain Insulin-sensitivity; Vascular Function

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Brain vascular function

  Change from placebo intervention at 2 hours after supplement intake

• Vascular function markers

  Change from fasting at 4 hours after supplement intake

• Cold pressure test

  Change from placebo at 4 hours after supplement intake

• Cardiometabolic risk markers (1)

  Change from placebo at 4 hours after supplement intake

• Cardiometabolic risk markers (2)

  Change from placebo at 4 hours after supplement intake

Study Arms (2)

Potassium nitrate

ACTIVE COMPARATOR

During this experimental day, men will receive 10 mmol of potassium nitrate

Dietary Supplement: Potassium nitrate

Placebo

PLACEBO COMPARATOR

During this experimental day, men will receive an isomolar dose of potassium chloride

Dietary Supplement: Placebo

Interventions

Potassium nitrate DIETARY_SUPPLEMENT

Acute intervention (5.5 hours)

Potassium nitrate

Placebo DIETARY_SUPPLEMENT

Acute intervention (5.5 hours)

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University Medical Center

Maastricht, Limburg, 6229 ER, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 35843050 DERIVED

MeSH Terms

Interventions

potassium nitrate

Study Officials

• Peter J. Joris, Dr

  Maastricht University

  PRINCIPAL INVESTIGATOR

• Ronald P.M. Mensink, Dr

  Maastricht University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: January 7, 2021
• Study Start: January 21, 2021
• Primary Completion: May 5, 2021
• Study Completion: May 5, 2021
• Last Updated: June 9, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)