Nitric OxideNCT04239482
Nutritional Supplementation and Insulin Sensitivity
A study testing L-arginine + Nitrate / Nitrite in people with Nitric Oxide and Insulin Sensitivity, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Nitric Oxide, Insulin Sensitivity, Vascular Function
- What is being tested?
- L-arginine + Nitrate / Nitrite
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Sep 2020to 1 Oct 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Center
Maastricht, Limburg, 6229 ER
About this study
Official title: Longer-term Effects of a Novel Nutritional Combination on Muscle Insulin Sensitivity and Mitochondrial Function, and Vascular Function in Abdominally Obese Subjects
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.
- Being tested
- L-arginine + Nitrate / Nitrite, Placebo
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-arginine + Nitrate / NitriteDietary supplement
Longer-term supplementation (8 weeks)
PlaceboDietary supplement
Longer-term supplementation (8 weeks)
| Study group | Role | What they receive |
|---|---|---|
| L-arginine + Nitrate/Nitrite | Experimental | Subjects will receive 1 L-arginine tablet per day and drink 35 mL of beetroot juice for 8 weeks. Receives: Dietary Supplement: L-arginine + Nitrate / Nitrite |
| Placebo | Placebo comparator | Subjects will receive 1 cellulose tablet per day and drink 35 mL of nitrate/nitrite depleted beetroot juice for 8 weeks. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in insulin sensitivity
Muscle insulin sensitivity
Measured: Change between 8-week placebo and 8-week intervention period
Secondary outcomes (13)
Change in muscle metabolism
Mitochondrial activity in muscle tissue
Measured: Change between 8-week placebo and 8-week intervention period
Change in physical functioning (1)
6 meter walking test
Measured: Change between 8-week placebo and 8-week intervention period
Change in physical functioning (2)
Timed up and go test
Measured: Change between 8-week placebo and 8-week intervention period
Change in physical functioning (3)
Handgrip strength test
Measured: Change between 8-week placebo and 8-week intervention period
Change in physical functioning (4)
Isokinetic muscle strength (BIODEX measurement)
Measured: Change between 8-week placebo and 8-week intervention period
Change in vascular function (1)
Flow-mediated vasodilation of the brachial artery
Measured: Change between 8-week placebo and 8-week intervention period
Change in vascular function (2)
Pulse wave analysis
Measured: Change between 8-week placebo and 8-week intervention period
Change in vascular function (3)
Pulse wave velocity
Measured: Change between 8-week placebo and 8-week intervention period
Change in vascular function (4)
Retinal microvascular calibers (Artery-to-Vein ratio)
Measured: Change between 8-week placebo and 8-week intervention period
Change in cardiometabolic risk markers (1)
Plasma markers for low-grade systemic inflammation (CRP)
Measured: Change between 8-week placebo and 8-week intervention period
Change in cardiometabolic risk markers (2)
Plasma markers for endothelial dysfunction (NOx)
Measured: Change between 8-week placebo and 8-week intervention period
Change in cardiometabolic risk markers (3)
24-h Systolic and Diastolic blood pressure
Measured: Change between 8-week placebo and 8-week intervention period
Change in continuous insulin sensitivity
36-h plasma glucose values
Measured: Change between 8-week placebo and 8-week intervention period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2020
- Study start1 Sep 2020
- Primary completion1 Oct 2020
- Study completion1 Oct 2020
Why it stopped: Due to covid-19 pandemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nitric OxideStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Nutricia Research
- Responsible party
- Sponsor
- Investigators
- Peter J Joris, PhD, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04239482
- Sponsor's protocol ID
- METC 19-085
- Status last verified
- Sep 2020
- First submitted
- 20 Dec 2019
- Last updated
- 11 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Longer-term Effects of a Novel Nutritional Combination on Muscle Insulin Sensitivity and Mitochondrial Function, and Vascular Function in Abdominally Obese Subjects
- ClinicalTrials.gov ID
- NCT04239482
- Acronym / sponsor ID
- METC 19-085
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to covid-19 pandemic
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Nutricia Research
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 1 Oct 2020 (actual)
- Study completion
- 1 Oct 2020 (actual)
- First posted
- 27 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L-arginine + Nitrate/Nitrite | Experimental | Dietary Supplement: L-arginine + Nitrate / NitriteSubjects will receive 1 L-arginine tablet per day and drink 35 mL of beetroot juice for 8 weeks. |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboSubjects will receive 1 cellulose tablet per day and drink 35 mL of nitrate/nitrite depleted beetroot juice for 8 weeks. |
Who may qualify
- Ages
- 50 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (11 listed)
- Current smoker, or smoking cessation < 12 months
- Diabetic patients
- Familial hypercholesterolemia
- Abuse of drugs
- More than 3 alcoholic consumptions per day
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-arginine + Nitrate / NitriteLonger-term supplementation (8 weeks) | Dietary supplement | L-arginine + Nitrate/Nitrite |
| PlaceboLonger-term supplementation (8 weeks) | Dietary supplement | Placebo |
Primary outcome
Change in insulin sensitivity
Time frame: Change between 8-week placebo and 8-week intervention period
Muscle insulin sensitivity
13 secondary outcomes
Change in muscle metabolism
Time frame: Change between 8-week placebo and 8-week intervention period
Change in physical functioning (1)
Time frame: Change between 8-week placebo and 8-week intervention period
Change in physical functioning (2)
Time frame: Change between 8-week placebo and 8-week intervention period
Change in physical functioning (3)
Time frame: Change between 8-week placebo and 8-week intervention period
Change in physical functioning (4)
Time frame: Change between 8-week placebo and 8-week intervention period
Change in vascular function (1)
Time frame: Change between 8-week placebo and 8-week intervention period
Change in vascular function (2)
Time frame: Change between 8-week placebo and 8-week intervention period
Change in vascular function (3)
Time frame: Change between 8-week placebo and 8-week intervention period
Change in vascular function (4)
Time frame: Change between 8-week placebo and 8-week intervention period
Change in cardiometabolic risk markers (1)
Time frame: Change between 8-week placebo and 8-week intervention period
Change in cardiometabolic risk markers (2)
Time frame: Change between 8-week placebo and 8-week intervention period
Change in cardiometabolic risk markers (3)
Time frame: Change between 8-week placebo and 8-week intervention period
Change in continuous insulin sensitivity
Time frame: Change between 8-week placebo and 8-week intervention period
Results and safety
The study was stopped early (reason given: Due to covid-19 pandemic). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter J Joris, PhD principal investigator
Maastricht University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing L-arginine + Nitrate / Nitrite in people with Nitric Oxide and Insulin Sensitivity, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Due to covid-19 pandemic). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in insulin sensitivity (time frame: Change between 8-week placebo and 8-week intervention period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2021.