E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Obesity, glucose intolerance, endothelial dysfunction |
Obesitas, glucose intolerantie, endotheeldysfunctie |
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E.1.1.1 | Medical condition in easily understood language |
Obesity, dysfunction of Sugar metabolism, dysfunction of the blood vessels |
obesitas, niet goed functioneren van de suikerstofwisseling, niet goed functioneren van de bloedvaten |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
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 |
In this study, we will investigate the influence of the amino acid L-arginine, which enhances release of nitric oxide in the body, on BAT activity and metabolism in healthy subjects with overweight. This will increase understanding on the effect of L-arginine and nitric oxide on overweight and BAT and hopefully, we will be more capable to treat overweight and obesity in the future.
Primary study parameters: 1) glucose uptake by brown adipose tissue 2) energy expenditure 3) fat mass
Furthermore, for each of these primary study parameters we will investigate whether the effect differs between South Asians and Caucasians.
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In dit onderzoek wordt gekeken naar de invloed van het aminozuur L-arginine, dat leidt tot verhoogde afgifte van stikstofmono-oxide in het lichaam, op de activiteit van bruin vet en de stofwisseling bij gezonde proefpersonen met licht overgewicht. Zo kunnen we meer te weten komen over de invloed van L-arginine en stikstofmono-oxide op overgewicht en bruin vet en kunnen we overgewicht in de toekomst mogelijk beter behandelen.
Primaire uitkomstmaten: 1) Glucoseopname door bruin vet 2) Energieverbruik 3) Vetmassa
Verder zal voor elk van deze primaire uitkomstmaten onderzocht worden of er een verschil is in het effect in Hindoestanen en Caucasiërs. |
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E.2.2 | Secondary objectives of the trial |
1) Thermoregulation (skin temperature, core temperature, skin perfusion and endothelium-dependent and -independent vasodilation) and endothelial function 2) Plasma lipids and glucose tolerance 3) Systemic inflammation and adipose tissue inflammation 4) Insulin signaling in muscle
Furthermore, for each of these secondary study parameters we will investigate whether the effect differs between South Asians and Caucasians |
1) Thermoregulatie (huidtemperatuur, kerntemperatuur, huidperfusie en endotheel-afhankelijke en -onafhankelijke vasodilatatie) en endotheelfunctie 2) Plasma lipiden en glucosetolerantie 3) Systemische inflammatie en inflammatie van vetweefsel 4) Insuline signaling in spier
Verder zal voor elk van deze secundaire uitkomstmaten onderzocht worden of er een verschil is in het effect in Hindoestanen en Caucasiërs |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Caucasian or South Asian ethnicity - Age: 35-50 years - Gender: male - BMI: 25-30 kg/m2 - Plasma glucose levels 2 h after OGTT between 7.8 and 11 mM (e.g. impaired glucose tolerance) - Plasma L-arginine levels 41 – 114 uM (i.e. within healthy range) - Good general health
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- Caucasische of Hindoestaanse ethniciteit - Leeftijd: 35-50 jaar - Geslacht: man - BMI: 25-30 kg/m2 - Plasma glucose levels 2 uur na OGTT tussen 7.8 en 11 mM (dus verminderde glucose tolerantie) - Plasma L-arginine levels 41 - 114 uM (dus binnen gezonde range) - goede algehele gezondheid |
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E.4 | Principal exclusion criteria |
- Type 2 diabetes (determined on basis of oral glucose tolerance test) - BMI > 30 kg/m2 - Plasma glucose levels 2 h after OGTT < 7.8 mM - Plasma L-arginine levels < 41 or > 114 uM - Use of beta-blockers < 1 month before start of study or during study - Participation in an intensive weight-loss program or vigorous exercise program during the last year before the start of the study - Abuse of drugs and/or alcohol - Hyperthyroidism or hypothyroidism - Systolic blood pressure < 90 mmHg - Haematocrit < 0.41 or > 0.51 l/l - Haemoglobin < 8.5 or > 11.0 - Creatinine (enzymatic method) < 45 or > 100 μmol/L - ASAT > 45 U/L - ALAT > 50 U/L - Alkaline phosphatase > 125 U/L - Gamma GT > 45 U/L - Participation in earlier research or medical examinations that included PET-CT scanning - Psychologically unstable subjects (as judged by the treating medical specialist) - Subjects with mental retardation (as judged by the treating medical specialist) - Subjects with severe behavior disorders (as judged by the treating medical specialist)
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- type 2 diabetes (bepaald op basis van orale glucose tolerantie test) - BMI > 30 kg/m2 - plasma glucose levels 2 uur na OGTT < 7.8 mM - Plasma L-arginine levels < 41 of > 114 uM - gebruik van beta-blockers < 1 maand voor start van de studie of tijdens de studie - deelname aan intensief programma voor gewichtsverlies of intensief trainingsprogramma tijdens het afgelopen jaar voor de studie - misbruik van drugs en/of alcohol - hyperthyreoïdie of hypothyreoidie - Systolische bloeddruk < 90 mmHg - Hematocriet < 0.41 or > 0.51 l/l - Hemoglobine < 8.5 or > 11.0 - Creatinine < 45 or > 100 μmol/L - ASAT > 45 U/L - ALAT > 50 U/L - Alkalisch fosfatase > 125 U/L - Gamma GT > 45 U/L - deelname aan eerder onderzoek waarin een PET-CT scan werd gedaan - psychologisch onstabiele mensen (zoals beoordeeld door de behandelend arts) - mentaal geretardeerde mensen (zoals beoordeeld door de behandelend arts) - mensen met ernstige gedragsproblemen (zoals beoordeeld door de behandelend arts) |
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E.5 End points |
E.5.1 | Primary end point(s) |
This study includes several parameters that are related to BAT activity, energy expenditure, thermoregulation, endothelial function and glucose tolerance/insulin sensitivity. Our main focus will be on BAT activity, which will be measured by means of static PET-CT scans. Our primary end points are:
1) glucose uptake by brown adipose tissue 2) energy expenditure 3) fat mass
Furthermore, for each of these primary study parameters we will investigate whether the effect differs between South Asians and Caucasians.
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In deze studie zullen verscheidene parameters worden onderzocht die geraleteerd zijn aan bruin vet activatie, energiegebruik, thermoregulatie, endotheelfunctie en glucosetolerantie/insuline gevoeligheid. Onze focus ligt met name op BAT activiteit, dat gemeten zal worden met statische PET-CT scans. Onze primaire uitkomstmaten zijn dan ook: 1) glucoseopname door bruin vet 2) energieverbruik 3) vetmassa
Verder kijken we voor elk van deze primaire uitkomstmaten of er verschillen zijn tussen Hindoestanen en Caucasiërs |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 6 weeks of treatment |
Na 6 weken behandeling |
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E.5.2 | Secondary end point(s) |
1) Thermoregulation (skin temperature, core temperature, skin perfusion and endothelium-dependent and -independent vasodilation) and endothelial function 2) Plasma lipids and glucose tolerance 3) Systemic inflammation and adipose tissue inflammation 4) Insulin signaling in muscle
Furthermore, for each of these secondary study parameters we will investigate whether the effect differs between South Asians and Caucasians. |
1) Thermoregulatie (huidtemperatuur, kerntemperatuur, huidperfusie en endotheel-afhankelijke en -onafhankelijke vasodilatatie) en endotheelfunctie 2) Plasma lipiden en glucosetolerantie 3) Systemische inflammatie en inflammatie van vetweefsel 4) Insuline signaling in spier
Verder zal voor elk van deze secundaire uitkomstmaten onderzocht worden of er een verschil is in het effect in Hindoestanen en Caucasiërs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 6 weeks of treatment |
Na 6 weken behandeling |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
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 | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | No |
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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |