E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Glucose tolerance |
Glucose tolerantie |
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E.1.1.1 | Medical condition in easily understood language |
Glucose tolerance: the switch between fatoxidation in the fasted state and glucose oxidation in the fed state. |
Glucose tolerantie : het kunnen wisselen tussen vetverbranding in de gevaste staat en suikerverbranding in de gevoede staat. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives are to investigate whether L-carnitine infusion may rescue lipid-induced insulin resistance and whether L-carnitine infusion is improving metabolic flexibility in the state of lipid-induced insulin resistance. |
Onderzoeken of infusie van L-carnitine lipiden geïnduceerde insuline resistentie kan tegengaan/voorkomen. |
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E.2.2 | Secondary objectives of the trial |
a secondary objective is to examine the molecular pathways of carnitine and acetylcarnitine, responsible for muscle insulin sensitivity. |
onderzoeken welke moleculaire pathways van carnitine and acetylcarnitine betrokken zijn bij insuline gevoeligheid |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Caucasian • Healthy (as determined by responsible physician based on a medical questionnaire) • Male • Age: 18-40 years • Normal BMI: 18-25 kg/m2 • Stable dietary habits • No use of medication interfering with investigated study parameters (as determined by responsible physician)
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Caucasian • Gezond • Man • Leeftijd: 18-40 jaar • Normaal BMI: 18-25 kg/m2 • Stabiele voedingsgewoonten • Geen medicijngebruik dat interfereert met de studieparameters |
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E.4 | Principal exclusion criteria |
• Female • Haemoglobin levels < 7.8 mmol/L • Uncontrolled hypertension • Use of anticoagulants • Engagement in exercise > 3 hours a week • Being vegetarian or vegan (because of altered whole body carnitine status) • Smoking • 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 • Medication use known to interfere with investigated study parameters • 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 • Subjects who do not want that their treating physician is informed
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• Vrouw • Haemoglobine levels < 7.8 mmol/L • Ongecontroleerde hypertensie • Gebruik van bloedverdunners • Sporten > 3 uur per week • Vegetarisch of veganistisch • Roken • Alcohol en/of drugsmisbruik • Onstabiel lichaamsgewicht (gewichtstoename of -afname > 5kg in de afgelopen 3 maanden) • Voedingsallergie of intolerantie • Deelname in een andere biomedische studie binnen 1 maand voor aanvang aan de huidige studie. • Medicijngebruik dat de veiligheid van de proefpersoon kan schaden tijdens de studie • Medicatie gebruik dat interfereert met de onderzochte parameters in de studie • Contra-indicaties voor de MRI • Proefpersonen die bloed willen doneren tijdens de studie of binnen 3 maanden voor aanvang van de studie • Proefpersonen die niet geïnformeerd willen worden over toevalsbevindingen • Proefpersonen die niet willen dat de huisarts geïnformeerd wordt over deelname aan de studie
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E.5 End points |
E.5.1 | Primary end point(s) |
- Whole body insulin sensitivity measured as GIR in µmol/kg/min during the stable period of the insulin phase of the clamp. - Peripheral insulin sensitivity measured as Rd in µmol/kg/min. - Metabolic flexibility (delta RER between basal and insulin stimulated state).
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Insuline gevoeligheid van het hele lichaam weergegeven als GIR in µmol/kg/min tijdens de stabiele fase van de insuline tijdens de clamp.
Perifere insuline gevoeligheid als Rd in µmol/kg/min
Metabole flexibiliteit ( delta RER tussen basaal en insuline) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 3 subjects |
na 3 proefpersonen |
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E.5.2 | Secondary end point(s) |
Maximal acetylcarnitine concentrations after exercise (measured using the 1H-MRS cycling measurement) -Metabolites in the blood before and during insulin stimulation (i.e. glucose, free fatty acids, triglycerides, cholesterol, insulin) - CrAT activity (measured in muscle biopsies) - Acylcarntine profiles (measured in muscle biopsies) - Lipid and lipid intermediates (measured in muscle biopsies)
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Maximale acetylcarnitine concentratie na inspanning (1H-MRS)
Metabolieten in het bloed tijdens de insuline stimulatie (glucose, FFA, triglyceriden, cholesterol, insuline)
CraT activiteit (spierbiopt)
Acetylcarnitine profiel (spierbiopt)
Lipiden en lipiden intermediaren (spierbiopt) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
na 10 proefpersonen |
na 10 proefpersonen |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |