Effects of Olanzapine standard oral tablets and orally disintegrating tablets on gut hormones, glucose metabolism and pituitary hormones.|
|- candidate number||2521|
|- NTR Number||NTR936|
|- Date ISRCTN created||11-apr-2007|
|- date ISRCTN requested||24-mrt-2007|
|- Date Registered NTR||15-mrt-2007|
|- Secondary IDs|| |
|- Public Title||Effects of Olanzapine standard oral tablets and orally disintegrating tablets on gut hormones, glucose metabolism and pituitary hormones.|
|- Scientific Title||Effects of Olanzapine standard oral tablets and orally disintegrating tablets on gut hormones, glucose metabolism and pituitary hormones.|
|- hypothesis||Novel antipsychotic drugs cause weight gain and type 2 diabetes mellitus in a large percentage of patients. The mechanism of the serious metabolic side effects of these drugs is unclear. Olanzapine orally disintegrating tablet has been found to cause less weight gain than olanzapine standard oral tablet. We hypothesized that theze two different forms of olanzapine differ in their effect of gut peptide release to explain their dramatically distinct impact on body weight. To further uncover the mechanism through which olanzapine causes weight gain and diabetes mellitus we also studied the impact of olanzapine on spontaneous release of various hormones (i.e. cortisol, prolactin, leptin, adinponectin, insulin, glucose, FFA and TG). |
|- Healt Condition(s) or Problem(s) studied||Diabetes Mellitus type 2 (DM type II), Insulin resistance, Antipsychotics|
|- Inclusion criteria||1. Healthy men without a positive family history of schizophrenia;|
2. Age between 20 and 40 yr.
3. Fasting plasma glucose < 6 mmol/L.
4. BMI between 20 and 26 kg/m2.
|- Exclusion criteria||1. Fasting plasma glucose > 6 mmol/L. |
2. BMI > 26 kg/m2.
3. Psychiatric disorder and/or use of antipsycotic or antidepressants drugs at present or in the past.
4. Gastrointestinal operations in the past.
5. Any significant chronic disease.
6. Renal, hepatic or endocrine disease.
7. Use of medication known to influence lipolysis and or glucose metabolism.
8. Total cholesterol > 7 mmol/L and or triglycerides > 2 mmol/L.
9. Recent weight changes or attempts to loose weight (>3 kg weight gain or loss, within the last 3 months).
10. Difficulties to insert an intravenous catheter.
11. Smoking (current).
12. Alcohol/drug abuse.
13. Severe claustrophobia.
14. Recent blood donation (within the last 2 months).
15. Recent participation in other research projects (within the last 3 months), participation in 2 or more projects in one year.
16. Extensive sporting activities (more than 10 hours of exercise per week).
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||10-apr-2006|
|- planned closingdate||26-sep-2006|
|- Target number of participants||12|
|- Interventions||Subjects are studied after intervention with olanzapine standard tablet (10mg/day for 8 days), Olanzapine orally disintegrating tablet (10 mg/day for 8 days) and without intervention (control). On day 7 subjects were submitted in the clinical reasearch unit, antropometric measures, body composition and fuel oxidation were measured. Blood samples for glucose, insulin, FFA en TG were drawn every 10 minutes, from 30 min before until 2 hours after dinner and breakfast. Blood samples for gut peptides were drawn every 20-30 minutes from 1 hour before until 4 hours after dinner and breakfast. Samples for determination of ACTH, cortisol, PRL (every 10 min), leptin (every 20 min) and adiponectin (every 30 min) were drawn from 00:00 until 12:hh h. Physical activity was recorded with actimeters for 3 days, during the different experimental conditions. |
|- Primary outcome||1. Antrhopometric measurements: BMI, WHR, Body composition.|
2. Indirect calorimetry: Resting energy expenditure, respiratory quotient, glucose and fat oxidation.
3. Plasma concentrations: Insulin, glucose, FFA, TG, PYY, PP, GLP-1, GLP-2, OXM, CCK, Ghrelin, ACTH, cortisol, PRL, Adiponectin, Leptin.
|- Secondary outcome||Physical activity.|
|- Trial web site||N/A|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES|| S. Vidarsdottir|
|- CONTACT for SCIENTIFIC QUERIES|| H. Pijl|
|- Sponsor/Initiator ||Leiden University Medical Center (LUMC), Department Endocrinology and Metabolism|
(Source(s) of Monetary or Material Support)
|Diabetes Research Fund , Eli Lilly Nederland B.V.|
|- Brief summary||This study was design to study the effect of two different forms of olanzapine, olanzpine standard tablet and olanzapine orally disintegrating tablet, on glucose and lipid homeostasis, gut peptides and various hormones in healthy, normal weight subjects without a positive family history of schizophrenia.|
|- Main changes (audit trail)|
|- RECORD||15-mrt-2007 - 2-sep-2009|
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