Glucose IntoleranceNCT03230812
Carnitine Supplementation in Type 2 Diabetic Patients
A study testing Carnitene (L-Carnitine or Levocarnitine) in people with Glucose Intolerance, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
the results from animal studies and preliminary human studies show that carnitine availability and acetylcarnitine concentrations are low in insulin resistant states such as with type 2 diabetes mellitus. However, in humans, carnitine supplementation is sometimes beneficial, but not in everyone. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Glucose Intolerance
- What is being tested?
- Carnitene (L-Carnitine or Levocarnitine)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Mar 2018to 11 Nov 2019
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and woman
- Age: 40-75 years
- Woman should be postmenopausal
- BMI: 25-38 kg/m2
- Stable dietary habits
- No use of medication interfering with investigated study parameters (as determined by responsible physician)
- Use of oral glucose lowering medication (metformin only or in combination with sulfonylurea agents)
Who cannot join
- Haemoglobin levels < 7.8 mmol/L
- Uncontrolled hypertension
- Use of anticoagulants
- Insulin dependent type 2 diabetic patients.
- No signs of active liver or kidney malfunction.
- Engagement in exercise > 3 hours a week
Show all 16Show fewer
- Being vegetarian or vegan (because of altered whole body carnitine status)
- Alcohol and/or drug abuse
- Unstable body weight (weight gain or loss > 5kg in the last 3 months)
- Significant food allergies/intolerances (seriously hampering study meals)
- Participation in another biomedical study within 1 month before the first study visit, which would possibly hamper our study results
- Medication use known to hamper subject's safety during the study procedures
- Subjects with contra-indications for MRI
- Subjects who intend to donate blood during the intervention or subjects who have donated blood less than three months before the start of the study
- Subjects who do not want to be informed about unexpected medical findings
- No signs of active diabetes-related co-morbidities like active cardiovascular diseases, active diabetic foot, polyneuropathy or retinopathy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Carnitine Supplementation as a Therapy to Improve Insulin Sensitivity in Type 2 Diabetic Patients With Low Carnitine Status
the results from animal studies and preliminary human studies show that carnitine availability and acetylcarnitine concentrations are low in insulin resistant states such as with type 2 diabetes mellitus. However, in humans, carnitine supplementation is sometimes beneficial, but not in everyone. We hypothesize that this variability in response might be due to differences between individuals in the amount of carnitine in the muscle i.e. subjects with a low initial carnitine status will benefit more from supplementation. The state of the art non-invasive magnetic resonance spectroscopy method allows us to identify patients muscle acetylcarnitine status. Here we aim to test whether carnitine improves insulin sensitivity, furthermore, whether acetylcarnitine concentration at baseline or other characteristics are associated with the response (in insulin sensitivity) to carnitine supplementation. Furthermore, we will examine the potentially positive effect of carnitine supplementation in type 2 diabetes patients on intrahepatic lipid content, acetylcarnitine formation, blood plasma metabolites, body composition, physical performance and quality of life
Read the detailed description
Rationale: 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. Thus, when substrate flux in the muscle is high, acetyl-CoA concentrations increase, leading to inhibition of pyruvate dehydrogenase (PDH) and thereby reducing glucose oxidation. The conversion of acetyl-CoA to acetylcarnitine relieves this acetyl-CoA pressure on PDH. In humans, carnitine supplementation is sometimes also beneficial, but not in everyone. Here we aim to test whether carnitine improves insulin sensitivity, furthermore, whether acetylcarnitine concentration at baseline or other characteristics are associated with the response (in insulin sensitivity) to carnitine supplementation. Furthermore, we will examine the potentially positive effect of carnitine supplementation in type 2 diabetes patients on intrahepatic lipid content, acetylcarnitine formation, blood plasma metabolites, body composition, physical performance and quality of life Objective: The primary objective is to investigate whether carnitine improves insulin sensitivity, furthermore, whether acetylcarnitine concentration at baseline or other characteristics are associated with the response (in insulin sensitivity) to carnitine supplementation. Furthermore, we will examine the potentially positive effect of carnitine supplementation in type 2 diabetes patients on intrahepatic lipid content, acetylcarnitine formation, blood plasma metabolites, body composition, physical performance and quality of life Study design: The current study is an interventional design with one study arm. Subjects will not be blinded for the intervention since all subjects will receive oral carnitine supplementation.
Study population: n=32, patient with type 2 diabetes (BMI 25-38, age 40-75 years) male and female will be included. Only subjects with relatively well-controlled non-insulin depended diabetes will be included.
Intervention (if applicable): Participants will be asked to take three chewing tablets of L-carnitine (330mg), three times a day (breakfast, lunch and dinner), for 96 days.
Main study parameters/endpoints: The primary study endpoints are insulin sensitivity and metabolic flexibility, measured by the hyperinsulinemic-euglycemic clamp. Secondary endpoints are maximal acetylcarnitine concentrations after exercise, Intrahepatic lipid content, body composition, metabolites in the blood before (i.e. glucose, free fatty acids, triglycerides, cholesterol, insulin), functional markers of physical performance, cognition, quality of life and quality of sleep.
- Conditions
- Glucose Intolerance
- Being tested
- Carnitene (L-Carnitine or Levocarnitine)
- 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.
Carnitene (L-Carnitine or Levocarnitine)Drug
All subjects will undergo oral Carnitene (L-Carnitine or levocarnitine) supplementation for 96 days.The total dosage of L-carnitine per day will be 2970mg. Consumption of the chewing tablets will be divided over the day. Intake of these chewing tablets will be during breakfast (990mg), lunch (990mg) and during diner (990mg). Since the chewing tablets are only available in concentrations of 330mg, participants have to consume 3 chewing tablets per meal, a total of 9 chewing tablets each day.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: carnitine intervention (in all participants) | Experimental | All subjects will undergo oral Carnitene (L-Carnitine or levocarnitine) supplementation for 96 days.The total dosage of L-carnitine per day will be 2970mg. Consumption of the chewing tablets will be divided over the day. Intake of these chewing tablets will be during breakfast (990mg), lunch (990mg) and during diner (990mg). Since the chewing tablets are only available in concentrations of 330mg, participants have to consume 3 chewing tablets per meal, a total of 9 chewing tablets each day. Receives: Drug: Carnitene (L-Carnitine or Levocarnitine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin sensitivity
Whole body insulin sensitivity measured as GIR in µmol/kg/min during the stable period of the insulin phase of the clamp.
- Hepatic insulin sensitivity measured as percent EGP supression in µmol/kg/min.
- Peripheral insulin sensitivity measured as Rd in µmol/kg/min.
Measured: 2-step hyperinsulinemische-egulycemische clamp (5.5 hours)
Metabolic flexibility
delta RER between basal and insulin stimulated state (both low (10mU) and high (40mU) insulin state
Measured: 2-step hyperinsulinemische-egulycemische clamp (5.5 hours)
Secondary outcomes (8)
Maximal acetylcarnitine concentrations after exercise
Measured using 1H-MRS after 30 minutes of cycling at 70% Wmax
Measured: 45 minutes
Body composition (bod pod)
determination fat mass and fat free mass
Measured: 30 minutes
Intrahepatic lipid content
Measured using 1H-MRS
Measured: 45 minutes
physical performance
distance covered in 6 minutes by walking
Measured: 6 minutes
physical performance
10 sit-standing exercises
Measured: 5 minutes
Quality of life
32-item questionnaire about Quality of Life. Reporting happens via a score on the so called combined quality of life score scale. The survey ranges between 32-160 points, with a higher score indicating a better QoL
Measured: 15 minutes
Quality of sleep
The Pittsburgh Sleep Quality Index (PSQI) was used to estimate quality of sleep (QoS) over the previous month. Reporting happens via a score on the so quality of sleep score scale. The score ranges between 0-21, with a lower score indicating a better sleep quality
Measured: 15 minutes
Cognitive performance
CANTAB
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2017
- Study start1 Mar 2018
- Primary completion11 Nov 2019
- Study completion11 Nov 2019
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
- Not applicable
- Intervention model
- Single group
- Model description
- One group with type 2 diabetic patients who will undergo oral L-carnitine supplementation for 96 days
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vera Schrauwen, Dr, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03230812
- Sponsor's protocol ID
- NL62791.068.17
- Status last verified
- Dec 2020
- First submitted
- 24 Jul 2017
- Last updated
- 7 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Carnitine Supplementation as a Therapy to Improve Insulin Sensitivity in Type 2 Diabetic Patients With Low Carnitine Status
- ClinicalTrials.gov ID
- NCT03230812
- Acronym / sponsor ID
- NL62791.068.17
- Conditions
- Glucose Intolerance
- Keywords
- Insulin sensitivity, Metabolic flexibility
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 11 Nov 2019 (actual)
- Study completion
- 11 Nov 2019 (actual)
- First posted
- 26 Jul 2017 (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.
the results from animal studies and preliminary human studies show that carnitine availability and acetylcarnitine concentrations are low in insulin resistant states such as with type 2 diabetes mellitus. However, in humans, carnitine supplementation is sometimes beneficial, but not in everyone. We hypothesize that this variability in response might be due to differences between individuals in the amount of carnitine in the muscle i.e. subjects with a low initial carnitine status will benefit more from supplementation. The state of the art non-invasive magnetic resonance spectroscopy method allows us to identify patients muscle acetylcarnitine status. Here we aim to test whether carnitine improves insulin sensitivity, furthermore, whether acetylcarnitine concentration at baseline or other characteristics are associated with the response (in insulin sensitivity) to carnitine supplementation. Furthermore, we will examine the potentially positive effect of carnitine supplementation in type 2 diabetes patients on intrahepatic lipid content, acetylcarnitine formation, blood plasma metabolites, body composition, physical performance and quality of life
Detailed description
Rationale: 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. Thus, when substrate flux in the muscle is high, acetyl-CoA concentrations increase, leading to inhibition of pyruvate dehydrogenase (PDH) and thereby reducing glucose oxidation. The conversion of acetyl-CoA to acetylcarnitine relieves this acetyl-CoA pressure on PDH. In humans, carnitine supplementation is sometimes also beneficial, but not in everyone. Here we aim to test whether carnitine improves insulin sensitivity, furthermore, whether acetylcarnitine concentration at baseline or other characteristics are associated with the response (in insulin sensitivity) to carnitine supplementation. Furthermore, we will examine the potentially positive effect of carnitine supplementation in type 2 diabetes patients on intrahepatic lipid content, acetylcarnitine formation, blood plasma metabolites, body composition, physical performance and quality of life Objective: The primary objective is to investigate whether carnitine improves insulin sensitivity, furthermore, whether acetylcarnitine concentration at baseline or other characteristics are associated with the response (in insulin sensitivity) to carnitine supplementation. Furthermore, we will examine the potentially positive effect of carnitine supplementation in type 2 diabetes patients on intrahepatic lipid content, acetylcarnitine formation, blood plasma metabolites, body composition, physical performance and quality of life Study design: The current study is an interventional design with one study arm. Subjects will not be blinded for the intervention since all subjects will receive oral carnitine supplementation.
Study population: n=32, patient with type 2 diabetes (BMI 25-38, age 40-75 years) male and female will be included. Only subjects with relatively well-controlled non-insulin depended diabetes will be included.
Intervention (if applicable): Participants will be asked to take three chewing tablets of L-carnitine (330mg), three times a day (breakfast, lunch and dinner), for 96 days.
Main study parameters/endpoints: The primary study endpoints are insulin sensitivity and metabolic flexibility, measured by the hyperinsulinemic-euglycemic clamp. Secondary endpoints are maximal acetylcarnitine concentrations after exercise, Intrahepatic lipid content, body composition, metabolites in the blood before (i.e. glucose, free fatty acids, triglycerides, cholesterol, insulin), functional markers of physical performance, cognition, quality of life and quality of sleep.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- One group with type 2 diabetic patients who will undergo oral L-carnitine supplementation for 96 days
| Arm | Type | Receives |
|---|---|---|
| Experimental: carnitine intervention (in all participants) | Experimental | Drug: Carnitene (L-Carnitine or Levocarnitine)All subjects will undergo oral Carnitene (L-Carnitine or levocarnitine) supplementation for 96 days.The total dosage of L-carnitine per day will be 2970mg. Consumption of the chewing tablets will be divided over the day. Intake of these chewing tablets will be during breakfast (990mg), lunch (990mg) and during diner (990mg). Since the chewing tablets are only available in concentrations of 330mg, participants have to consume 3 chewing tablets per meal, a total of 9 chewing tablets each day. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Men and woman
- Age: 40-75 years
- Woman should be postmenopausal
- BMI: 25-38 kg/m2
- Stable dietary habits
Key exclusion criteria (16 listed)
- Haemoglobin levels < 7.8 mmol/L
- Uncontrolled hypertension
- Use of anticoagulants
- Insulin dependent type 2 diabetic patients.
- No signs of active liver or kidney malfunction.
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 |
|---|---|---|
| Carnitene (L-Carnitine or Levocarnitine)All subjects will undergo oral Carnitene (L-Carnitine or levocarnitine) supplementation for 96 days.The total dosage of L-carnitine per day will be 2970mg. Consumption of the chewing tablets will be divided over the day. Intake of these chewing tablets will be during breakfast (990mg), lunch (990mg) and during diner (990mg). Since the chewing tablets are only available in concentrations of 330mg, participants have to consume 3 chewing tablets per meal, a total of 9 chewing tablets each day. | Drug | Experimental: carnitine intervention (in all participants) |
Primary outcome
Insulin sensitivity
Time frame: 2-step hyperinsulinemische-egulycemische clamp (5.5 hours)
Whole body insulin sensitivity measured as GIR in µmol/kg/min during the stable period of the insulin phase of the clamp. * Hepatic insulin sensitivity measured as percent EGP supression in µmol/kg/min. * Peripheral insulin sensitivity measured as Rd in µmol/kg/min.
Metabolic flexibility
Time frame: 2-step hyperinsulinemische-egulycemische clamp (5.5 hours)
delta RER between basal and insulin stimulated state (both low (10mU) and high (40mU) insulin state
8 secondary outcomes
Maximal acetylcarnitine concentrations after exercise
Time frame: 45 minutes
Body composition (bod pod)
Time frame: 30 minutes
Intrahepatic lipid content
Time frame: 45 minutes
physical performance
Time frame: 6 minutes
physical performance
Time frame: 5 minutes
Quality of life
Time frame: 15 minutes
Quality of sleep
Time frame: 15 minutes
Cognitive performance
Time frame: 1 hour
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 7 Dec 2020.
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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 Schrauwen, Dr 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 Carnitene (L-Carnitine or Levocarnitine) 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 7 inclusion and 16 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 7 Dec 2020. 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. 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?
Insulin sensitivity (time frame: 2-step hyperinsulinemische-egulycemische clamp (5.5 hours)). 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 7 Dec 2020.