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Nitrate and Brain Insulin-Sensitivity (NO-BRAINS)

Primary Purpose

Nitrate, Brain Insulin-sensitivity, Vascular Function

Status

Completed

Phase

Not Applicable

Locations

Netherlands

Study Type

Interventional

Intervention

Potassium nitrate

Placebo

About this trial

This is an interventional prevention trial for Nitrate

Eligibility Criteria

18 Years - 60 Years (Adult)MaleAccepts Healthy Volunteers

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.

Sites / Locations

Maastricht University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Potassium nitrate

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Brain insulin sensitivity

MRI arterial spin labeling, cerebral blood flow measurements before and after a nasal insulin spray

Secondary Outcome Measures

Brain vascular function

MRI arterial spin labeling, cerebral blood flow measurements

Vascular function markers

Flow-mediated vasodilation (FMD) of the brachial and femoral artery

Cold pressure test

Carotid artery response to cold pressure test

Cardiometabolic risk markers (1)

Plasma markers for low-grade systemic inflammation (CRP)

Cardiometabolic risk markers (2)

Plasma marker for endothelial dysfunction (NOx)

Cardiometabolic risk markers (3)

Office blood pressure

Cardiometabolic risk markers (4)

Plasma brain derived neurotrophic factor (BDNF)

Postprandial metabolism (1)

Serum lipid metabolism

Postprandial metabolism (2)

Plasma glucose metabolism

Full Information

NCT ID

NCT04700241

First Posted

January 6, 2021

Last Updated

June 8, 2021

Sponsor

Maastricht University Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT04700241

Brief Title

Nitrate and Brain Insulin-Sensitivity

Acronym

NO-BRAINS

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Completed

Study Start Date

January 21, 2021 (Actual)

Primary Completion Date

May 5, 2021 (Actual)

Study Completion Date

May 5, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Maastricht University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nitrate, Brain Insulin-sensitivity, Vascular Function

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Potassium nitrate

Arm Type

Active Comparator

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Dietary Supplement

Intervention Name(s)

Potassium nitrate

Intervention Description

Acute intervention (5.5 hours)

Intervention Type

Dietary Supplement

Intervention Name(s)

Placebo

Intervention Description

Acute intervention (5.5 hours)

Primary Outcome Measure Information:

Title

Brain insulin sensitivity

Description

MRI arterial spin labeling, cerebral blood flow measurements before and after a nasal insulin spray

Time Frame

Change from placebo intervention at 2 hours after supplement intake

Secondary Outcome Measure Information:

Title

Brain vascular function

Description

MRI arterial spin labeling, cerebral blood flow measurements

Time Frame

Change from placebo intervention at 2 hours after supplement intake

Title

Vascular function markers

Description

Flow-mediated vasodilation (FMD) of the brachial and femoral artery

Time Frame

Change from fasting at 4 hours after supplement intake

Title

Cold pressure test

Description

Carotid artery response to cold pressure test

Time Frame

Change from placebo at 4 hours after supplement intake

Title

Cardiometabolic risk markers (1)

Description

Plasma markers for low-grade systemic inflammation (CRP)

Time Frame

Change from placebo at 4 hours after supplement intake

Title

Cardiometabolic risk markers (2)

Description

Plasma marker for endothelial dysfunction (NOx)

Time Frame

Change from placebo at 4 hours after supplement intake

Title

Cardiometabolic risk markers (3)

Description

Office blood pressure

Time Frame

Change from placebo at 4 hours after supplement intake

Title

Cardiometabolic risk markers (4)

Description

Plasma brain derived neurotrophic factor (BDNF)

Time Frame

During the 5.5 hours following supplement intake

Title

Postprandial metabolism (1)

Description

Serum lipid metabolism

Time Frame

During the 5.5 hours following supplement intake

Title

Postprandial metabolism (2)

Description

Plasma glucose metabolism

Time Frame

During the 5.5 hours following supplement intake

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Peter J. Joris, Dr

Organizational Affiliation

Maastricht University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Ronald P.M. Mensink, Dr

Organizational Affiliation

Maastricht University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Maastricht University Medical Center

City

Maastricht

State/Province

Limburg

ZIP/Postal Code

6229 ER

Country

Netherlands

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35843050

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.

Results Reference

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Nitrate and Brain Insulin-Sensitivity

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