Nitrate and Brain Insulin-Sensitivity

NCT ID: NCT04700241

Last Updated: 2021-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-21
• Study Completion Date: 2021-05-05

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Potassium nitrate

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

Group Type: ACTIVE_COMPARATOR

Potassium nitrate

Intervention Type: DIETARY_SUPPLEMENT

Acute intervention (5.5 hours)

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Acute intervention (5.5 hours)

Interventions

Potassium nitrate

Acute intervention (5.5 hours)

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Acute intervention (5.5 hours)

Intervention Type: DIETARY_SUPPLEMENT

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter J. Joris, Dr

Role: PRINCIPAL_INVESTIGATOR

Maastricht University

Ronald P.M. Mensink, Dr

Role: PRINCIPAL_INVESTIGATOR

Maastricht University

Locations

Maastricht University Medical Center

Maastricht, Limburg, Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 35843050 (View on PubMed)

Other Identifiers

METC 20-0.78

Identifier Type: -

Identifier Source: org_study_id