Glucose IntoleranceNCT02072759
Acetylcarnitine and Metabolic Flexibility
A study testing Carnitine supplement in people with Glucose Intolerance, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Insulin resistant subjects and type 2 diabetic patients are characterized by a decreased metabolic flexibility: a reduced capability to switch from fat oxidation in the basal state to carbohydrate oxidation in the insulin-stimulated state. Read more about this study
- Who is it for?
- Ages 40 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Glucose Intolerance
- What is being tested?
- Carnitine supplement
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2014to Jun 2016
- 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 40 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 40-70 years
- Overweight/obese, BMI 25-35 kg/m2
- Stable dietary habits
- Generally healthy with no medication use that interferes with metabolism
Who cannot join
- Fasting plasma glucose >7.1 mmol/l
- Haemoglobin <7.8 mmol/l
- Hypertension: blood pressure > 140 mmHg systolic or 90 mmHg diastolic
- Cardiac problems, such as angina pectoris, cardiac infarction and arrhythmias
- Plasma creatinine concentration higher than 115 micromol/l (in men) en 100 micromol (in women).
- Any medical condition requiring treatment and/or medication that interferes with investigated parameters
Show all 11Show fewer
- Unstable body weight (weight gain or loss > 3 kg in the past three months)
- Participation in another biomedical study within 1 month prior to the screening visit
- Subjects with contra-indication for MRI
- Subjects, who do not want to be informed about unexpected medical findings, or do not wish that their treating physician is informed, cannot participate in the study.
- Subject are not allowed to donate blood three months prior to the start of the study and three months after finishing the study.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Center
Maastricht, Limburg, 6229 ER
About this study
Official title: Preservation of Metabolic Flexibility by Acetylcarnitine Formation
Insulin resistant subjects and type 2 diabetic patients are characterized by a decreased metabolic flexibility: a reduced capability to switch from fat oxidation in the basal state to carbohydrate oxidation in the insulin-stimulated state. This metabolic inflexibility is an early hallmark in the development of diabetes. Recent evidence suggests that a low carnitine availability may limit acetylcarnitine formation, thereby reducing metabolic flexibility. We propose to test the hypothesis that metabolic inflexibility in pre-diabetic subjects and diabetic patients is due to a reduced capacity to form acetylcarnitines.
Read the detailed description
Background: Insulin resistant subjects and type 2 diabetic patients are characterized by a decreased metabolic flexibility: a reduced capability to switch from fat oxidation in the basal state to carbohydrate oxidation in the insulin-stimulated state. This metabolic inflexibility is an early hallmark in the development of diabetes. Recent evidence suggests that low carnitine availability may limit acetylcarnitine formation, thereby reducing metabolic flexibility.
Objectives: We will investigate whether subjects with impaired glucose tolerance (IGT) show a diminished capacity to form acetylcarnitine in the face of high substrate availability. Therefore, we will use a novel non-invasive 1H-Magnetic Resonance Spectroscopy (1H-MRS) protocol to determine in vivo, and in time, the formation of acetylcarnitine in skeletal muscle. Additionally, we will examine whether carnitine supplementation increases the capacity to form acetylcarnitine and improves metabolic flexibility and insulin sensitivity in IGT subjects.
Study design: 12 subjects with IGT will be included and will be subjected to either placebo- or carnitine treatment (daily capsules with 2g of L-carnitine or placebo) in a randomized, placebo-controlled, double blind crossover design. After both interventions, acetylcarnitine formation after a mixed meal will be determined by 1H-MRS and meal-induced changes in fat and glucose oxidation by indirect calorimetry. The maximal acetylcarnitine formation will be measured after a cycling test via 1H-MRS. A hyperinsulinemic-euglycemic clamp will be performed to determine insulin sensitivity. Biopsies will be taken to measure free carnitine and carnitine acetyltransferase (CrAT) activity. To investigate whether differences in acetylcarnitine formation may be involved in variations in glucose tolerance, twelve control subjects, matched for BMI and age but glucose tolerant (based on oral glucose tolerance test, according to WHO criteria) will also be included and will undergo all measurements once without any intervention.
- Conditions
- Glucose Intolerance
- Being tested
- Carnitine supplement, Placebo
- Keywords
- Insulin sensitivity, Metabolic flexibility
- Medical subject headings
- Glucose Intolerance, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carnitine supplementDietary supplement
Carnitine supplement (oral ingestion with meals)
Total dosage of 2g carnitine per day for 36 days.
- 1 carnitine supplement at breakfast (500mg)
- 1 carnitine supplement at lunch (500mg)
- 2 carnitine supplements at diner (2x 500mg=1000mg)
PlaceboDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Carnitine supplement | Experimental | Carnitine supplement Receives: Dietary Supplement: Carnitine supplement |
| Placebo | Placebo comparator | Placebo supplement Receives: Dietary Supplement: Placebo |
| Healthy control | No intervention | Healthy control group |
What is being measured
The primary outcome is the main question the study is designed to answer.
metabolic flexibility
delta RER between basal and insulin-stimulated state)
Measured: 36 days
Insulin sensitivity
Measured: 36 days
Secondary outcomes (4)
exercise-induced acetylcarnitine concentrations
Measured: 36 days
meal-induced acetylcarnitine formation
Measured: 36 days
CrAT activity
determined in muscle biopsy samples
Measured: 36 days
fasted blood plasma levels of FFA, triglycerides and glucose and post-meal area under the curve (AUC)
Measured: 36 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2014 (estimated)
- Study startMar 2014
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glucose IntoleranceStudies 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- European Foundation for the Study of Diabetes
- Responsible party
- Sponsor
- Investigators
- Vera B Schrauwen, PhD, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02072759
- Sponsor's protocol ID
- NL44572.068.13
- Status last verified
- Jun 2015
- First submitted
- 25 Feb 2014
- Last updated
- 14 Jul 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preservation of Metabolic Flexibility by Acetylcarnitine Formation
- ClinicalTrials.gov ID
- NCT02072759
- Acronym / sponsor ID
- NL44572.068.13
- Conditions
- Glucose Intolerance
- Keywords
- Insulin sensitivity, Metabolic flexibility
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- European Foundation for the Study of Diabetes
- Study start
- Mar 2014
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 27 Feb 2014 (estimated)
- 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.
Insulin resistant subjects and type 2 diabetic patients are characterized by a decreased metabolic flexibility: a reduced capability to switch from fat oxidation in the basal state to carbohydrate oxidation in the insulin-stimulated state. This metabolic inflexibility is an early hallmark in the development of diabetes. Recent evidence suggests that a low carnitine availability may limit acetylcarnitine formation, thereby reducing metabolic flexibility. We propose to test the hypothesis that metabolic inflexibility in pre-diabetic subjects and diabetic patients is due to a reduced capacity to form acetylcarnitines.
Detailed description
Background: Insulin resistant subjects and type 2 diabetic patients are characterized by a decreased metabolic flexibility: a reduced capability to switch from fat oxidation in the basal state to carbohydrate oxidation in the insulin-stimulated state. This metabolic inflexibility is an early hallmark in the development of diabetes. Recent evidence suggests that low carnitine availability may limit acetylcarnitine formation, thereby reducing metabolic flexibility.
Objectives: We will investigate whether subjects with impaired glucose tolerance (IGT) show a diminished capacity to form acetylcarnitine in the face of high substrate availability. Therefore, we will use a novel non-invasive 1H-Magnetic Resonance Spectroscopy (1H-MRS) protocol to determine in vivo, and in time, the formation of acetylcarnitine in skeletal muscle. Additionally, we will examine whether carnitine supplementation increases the capacity to form acetylcarnitine and improves metabolic flexibility and insulin sensitivity in IGT subjects.
Study design: 12 subjects with IGT will be included and will be subjected to either placebo- or carnitine treatment (daily capsules with 2g of L-carnitine or placebo) in a randomized, placebo-controlled, double blind crossover design. After both interventions, acetylcarnitine formation after a mixed meal will be determined by 1H-MRS and meal-induced changes in fat and glucose oxidation by indirect calorimetry. The maximal acetylcarnitine formation will be measured after a cycling test via 1H-MRS. A hyperinsulinemic-euglycemic clamp will be performed to determine insulin sensitivity. Biopsies will be taken to measure free carnitine and carnitine acetyltransferase (CrAT) activity. To investigate whether differences in acetylcarnitine formation may be involved in variations in glucose tolerance, twelve control subjects, matched for BMI and age but glucose tolerant (based on oral glucose tolerance test, according to WHO criteria) will also be included and will undergo all measurements once without any intervention.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Carnitine supplement | Experimental | Dietary Supplement: Carnitine supplementCarnitine supplement |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboPlacebo supplement |
| Healthy control | No intervention | –Healthy control group |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 40-70 years
- Overweight/obese, BMI 25-35 kg/m2
- Stable dietary habits
- Generally healthy with no medication use that interferes with metabolism
Key exclusion criteria (11 listed)
- Fasting plasma glucose >7.1 mmol/l
- Haemoglobin <7.8 mmol/l
- Hypertension: blood pressure > 140 mmHg systolic or 90 mmHg diastolic
- Cardiac problems, such as angina pectoris, cardiac infarction and arrhythmias
- Plasma creatinine concentration higher than 115 micromol/l (in men) en 100 micromol (in women).
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 |
|---|---|---|
| Carnitine supplementCarnitine supplement (oral ingestion with meals) Total dosage of 2g carnitine per day for 36 days. * 1 carnitine supplement at breakfast (500mg) * 1 carnitine supplement at lunch (500mg) * 2 carnitine supplements at diner (2x 500mg=1000mg) | Dietary supplement | Carnitine supplement |
| Placebo | Dietary supplement | Placebo |
Primary outcome
metabolic flexibility
Time frame: 36 days
delta RER between basal and insulin-stimulated state)
Insulin sensitivity
Time frame: 36 days
4 secondary outcomes
exercise-induced acetylcarnitine concentrations
Time frame: 36 days
meal-induced acetylcarnitine formation
Time frame: 36 days
CrAT activity
Time frame: 36 days
fasted blood plasma levels of FFA, triglycerides and glucose and post-meal area under the curve (AUC)
Time frame: 36 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2016.
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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.
Vera B Schrauwen, 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 Carnitine supplement in people with Glucose Intolerance, 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 4 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: finished, as of the sponsor's last update on 14 Jul 2016. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
metabolic flexibility (time frame: 36 days). The study lists 2 primary outcomes in all. 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 14 Jul 2016.