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Nutritional Supplementation and Insulin Sensitivity

Primary Purpose

Nitric Oxide, Insulin Sensitivity, Vascular Function

Status
Terminated
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
L-arginine + Nitrate / Nitrite
Placebo
Sponsored by
Maastricht University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Nitric Oxide

Eligibility Criteria

50 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Aged between 50-70 years
  • Men and postmenopausal (two or more years after last menstruation) women
  • Waist circumference for men 3 102 cm and for women 3 88 cm (abdominally obese)
  • Impaired fasting glucose concentrations (between 5.6 - 7.0 mmol/L in accordance with the American Diabetes Association guidelines for prediabetes) at two screening visits
  • Fasting serum total cholesterol < 8.0 mmol/L
  • 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
  • No difficult venipuncture as evidenced during the screening visit
  • Willingness to give up the use of antibacterial mouth wash or antibacterial toothpaste, chewing-gum and tongue-scraping during the study

Exclusion Criteria:

  • Current smoker, or smoking cessation < 12 months
  • Diabetic patients
  • Familial hypercholesterolemia
  • Abuse of drugs
  • More than 3 alcoholic consumptions per day
  • Use of dietary supplements known to interfere with the main study outcomes as judged by the principal investigators
  • Use of anticoagulant drugs or drugs to treat blood pressure, lipid/glucose metabolism
  • Use of an investigational product within another biomedical intervention trial within the previous 1-month
  • Intolerance or allergy to the ingredients of the intervention products
  • Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease (COPD), 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

Sites / Locations

  • Maastricht University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

L-arginine + Nitrate/Nitrite

Placebo

Arm Description

Subjects will receive 1 L-arginine tablet per day and drink 35 mL of beetroot juice for 8 weeks.

Subjects will receive 1 cellulose tablet per day and drink 35 mL of nitrate/nitrite depleted beetroot juice for 8 weeks.

Outcomes

Primary Outcome Measures

Change in insulin sensitivity
Muscle insulin sensitivity

Secondary Outcome Measures

Change in muscle metabolism
Mitochondrial activity in muscle tissue
Change in physical functioning (1)
6 meter walking test
Change in physical functioning (2)
Timed up and go test
Change in physical functioning (3)
Handgrip strength test
Change in physical functioning (4)
Isokinetic muscle strength (BIODEX measurement)
Change in vascular function (1)
Flow-mediated vasodilation of the brachial artery
Change in vascular function (2)
Pulse wave analysis
Change in vascular function (3)
Pulse wave velocity
Change in vascular function (4)
Retinal microvascular calibers (Artery-to-Vein ratio)
Change in cardiometabolic risk markers (1)
Plasma markers for low-grade systemic inflammation (CRP)
Change in cardiometabolic risk markers (2)
Plasma markers for endothelial dysfunction (NOx)
Change in cardiometabolic risk markers (3)
24-h Systolic and Diastolic blood pressure
Change in continuous insulin sensitivity
36-h plasma glucose values

Full Information

First Posted
December 20, 2019
Last Updated
June 8, 2021
Sponsor
Maastricht University Medical Center
Collaborators
Nutricia Research
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1. Study Identification

Unique Protocol Identification Number
NCT04239482
Brief Title
Nutritional Supplementation and Insulin Sensitivity
Official Title
Longer-term Effects of a Novel Nutritional Combination on Muscle Insulin Sensitivity and Mitochondrial Function, and Vascular Function in Abdominally Obese Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Terminated
Why Stopped
Due to covid-19 pandemic
Study Start Date
September 1, 2020 (Actual)
Primary Completion Date
October 1, 2020 (Actual)
Study Completion Date
October 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Maastricht University Medical Center
Collaborators
Nutricia Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Type 2 diabetes mellitus (T2DM) is a progressive disease and early intervention and prevention strategies are therefore very important. An important early hallmark in the development of T2DM is insulin resistance. Since the majority of postprandial glucose disposal occurs in skeletal muscle, improving muscle insulin sensitivity will thus have a major impact on disease prevention. Abdominally obese men and women have an increased risk to develop T2DM, and are also characterized by an impaired vascular function. This may hamper proper delivery of insulin, glucose and oxygen to muscles, thereby contributing to - and possibly causing - muscle insulin resistance. Earlier it has been shown that supplementation with L- arginine improves vascular function by improving nitric oxide (NO) bioavailability. These NO- mediated beneficial effects on vascular function may improve delivery of insulin, glucose and oxygen to the muscle tissue, thereby improving muscle insulin sensitivity and mitochondrial function. However, the doses needed of this amino acid cannot be provided by regular diets or supplements, also due to the bitter taste of L-arginine. Alternatively, smaller amounts of L- arginine with a specific combination of other nutritional components (i.e. nitrate and nitrite), which are already part of the regular diet and support alternative pathways to improve NO- mediated vascular function, may also induce beneficial effects. The investigators now hypothesize that in abdominally obese adults with impaired fasting glucose concentrations L-arginine combined with nitrate/nitrite increases muscle insulin sensitivity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nitric Oxide, Insulin Sensitivity, Vascular Function, L-arginine, Nitrate / Nitrite

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
L-arginine + Nitrate/Nitrite
Arm Type
Experimental
Arm Description
Subjects will receive 1 L-arginine tablet per day and drink 35 mL of beetroot juice for 8 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects will receive 1 cellulose tablet per day and drink 35 mL of nitrate/nitrite depleted beetroot juice for 8 weeks.
Intervention Type
Dietary Supplement
Intervention Name(s)
L-arginine + Nitrate / Nitrite
Intervention Description
Longer-term supplementation (8 weeks)
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Longer-term supplementation (8 weeks)
Primary Outcome Measure Information:
Title
Change in insulin sensitivity
Description
Muscle insulin sensitivity
Time Frame
Change between 8-week placebo and 8-week intervention period
Secondary Outcome Measure Information:
Title
Change in muscle metabolism
Description
Mitochondrial activity in muscle tissue
Time Frame
Change between 8-week placebo and 8-week intervention period
Title
Change in physical functioning (1)
Description
6 meter walking test
Time Frame
Change between 8-week placebo and 8-week intervention period
Title
Change in physical functioning (2)
Description
Timed up and go test
Time Frame
Change between 8-week placebo and 8-week intervention period
Title
Change in physical functioning (3)
Description
Handgrip strength test
Time Frame
Change between 8-week placebo and 8-week intervention period
Title
Change in physical functioning (4)
Description
Isokinetic muscle strength (BIODEX measurement)
Time Frame
Change between 8-week placebo and 8-week intervention period
Title
Change in vascular function (1)
Description
Flow-mediated vasodilation of the brachial artery
Time Frame
Change between 8-week placebo and 8-week intervention period
Title
Change in vascular function (2)
Description
Pulse wave analysis
Time Frame
Change between 8-week placebo and 8-week intervention period
Title
Change in vascular function (3)
Description
Pulse wave velocity
Time Frame
Change between 8-week placebo and 8-week intervention period
Title
Change in vascular function (4)
Description
Retinal microvascular calibers (Artery-to-Vein ratio)
Time Frame
Change between 8-week placebo and 8-week intervention period
Title
Change in cardiometabolic risk markers (1)
Description
Plasma markers for low-grade systemic inflammation (CRP)
Time Frame
Change between 8-week placebo and 8-week intervention period
Title
Change in cardiometabolic risk markers (2)
Description
Plasma markers for endothelial dysfunction (NOx)
Time Frame
Change between 8-week placebo and 8-week intervention period
Title
Change in cardiometabolic risk markers (3)
Description
24-h Systolic and Diastolic blood pressure
Time Frame
Change between 8-week placebo and 8-week intervention period
Title
Change in continuous insulin sensitivity
Description
36-h plasma glucose values
Time Frame
Change between 8-week placebo and 8-week intervention period

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Aged between 50-70 years Men and postmenopausal (two or more years after last menstruation) women Waist circumference for men 3 102 cm and for women 3 88 cm (abdominally obese) Impaired fasting glucose concentrations (between 5.6 - 7.0 mmol/L in accordance with the American Diabetes Association guidelines for prediabetes) at two screening visits Fasting serum total cholesterol < 8.0 mmol/L 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 No difficult venipuncture as evidenced during the screening visit Willingness to give up the use of antibacterial mouth wash or antibacterial toothpaste, chewing-gum and tongue-scraping during the study Exclusion Criteria: Current smoker, or smoking cessation < 12 months Diabetic patients Familial hypercholesterolemia Abuse of drugs More than 3 alcoholic consumptions per day Use of dietary supplements known to interfere with the main study outcomes as judged by the principal investigators Use of anticoagulant drugs or drugs to treat blood pressure, lipid/glucose metabolism Use of an investigational product within another biomedical intervention trial within the previous 1-month Intolerance or allergy to the ingredients of the intervention products Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease (COPD), 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter J Joris, PhD
Organizational Affiliation
Maastricht University Medical Center
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
No

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Nutritional Supplementation and Insulin Sensitivity

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