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Completed

NCT Number: NCT04700241

Nitrate and Brain Insulin-Sensitivity

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.

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Key information

Age range

18 year–60 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Maastricht University Medical Center

Maastricht, Limburg, 6229 ER, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Potassium nitrate

Dietary Supplement

Acute intervention (5.5 hours)

Placebo

Dietary Supplement

Acute intervention (5.5 hours)

Primary outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Maastricht University Medical Center

Other

Registry information

Official study title

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

Acronym: NO-BRAINS

Important dates

Study start
2021
Primary completion
2021
Study completion
2021
First posted
Jan 7, 2021
Registry last updated
Jun 9, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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