Effects of olanzapine standard oral tablets and orally disintegrating tablets on gut hormones, glucose metabolism and pituitary hormones

ISRCTN	ISRCTN17632637
DOI	https://doi.org/10.1186/ISRCTN17632637
Protocol serial number	N/A
Sponsor	Leiden University Medical Centre (LUMC) (The Netherlands)
Funders	Eli Lilly (The Netherlands), Dutch Diabetes Research Fund (The Netherlands)

Submission date: 11/04/2007
Registration date: 11/04/2007
Last edited: 05/11/2010

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr S Vidarsdottir
Scientific

Department Endocrinology and Metabolism
Leiden University Medical Centre, C4-R
P.O. Box 9600
Leiden
2300 RC
Netherlands

Phone	+31 (0)71 526 3082
Email	s.vidarsdottir@lumc.nl

Study information

Primary study design	Interventional
Study design	Randomised, active controlled, crossover trial
Secondary study design	Randomised controlled trial
Scientific title
Study objectives	Novel antipsychotic drugs cause weight gain and type two 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 hypothesised that these 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, Free Fatty Acids [FFA] and Triglycerides [TG]).
Ethics approval(s)	Approval received from the ethics board in the Leiden University Medical Center (LUMC)(Commissie Medische Ethiek LUMC) on the 28th February 2006 (ref: P06-005/YR/kdw).
Health condition(s) or problem(s) studied	Diabetes Mellitus type two (DM type II)
Intervention	Subjects are studied after intervention with olanzapine standard tablet (10 mg/day for eight days), olanzapine orally disintegrating tablet (10 mg/day for eight days) and without intervention (control). On day seven subjects were submitted in the clinical reasearch unit, antropometric measures, body composition and fuel oxidation were measured. Blood samples for glucose, insulin, FFA and TG were drawn every ten minutes, from 30 minutes before until two hours after dinner and breakfast. Blood samples for gut peptides were drawn every 20 to 30 minutes from one hour before until four hours after dinner and breakfast. Samples for determination of Adrenocorticotropic Hormone (ACTH), cortisol, Prolactin (PRL) (every ten minutes), leptin (every 20 minutes) and adiponectin (every 30 minutes) were drawn from 00:00 until 12:hh hours. Physical activity was recorded with actimeters for three days, during the different experimental conditions.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Olanzapine standard oral tablets and orally disintegrating tablets
Primary outcome measure(s)	1. Antrhopometric measurements: BMI, Waist:Hip Ratio (WHR), body composition 2. Indirect calorimetry: Resting energy expenditure, respiratory quotient, glucose and fat oxidation 3. Plasma concentrations: insulin, glucose, FFA, TG, Peptide YY3-36 (PYY), Pancreatic Polypeptide (PP), Glucagon-like peptide-1 (GLP-1), Glucagon-like peptide-2 (GLP-2), Oxyntomodulin (OXM), Cholecystokinin (CCK), Ghrelin, ACTH, cortisol, PRL, Adiponectin, Leptin All primary end points were measured on day seven and eight of the intervention.
Key secondary outcome measure(s)	Physical activity, this was measured for three days between day one and four of the intervention.
Completion date	26/09/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Male
Target sample size at registration	12
Key inclusion criteria	1. Healthy men without a positive family history of schizophrenia 2. Age between 20 and 40 years 3. Fasting plasma glucose less than 6 mmol/L 4. Body Mass Index (BMI) between 20 and 26 kg/m^2
Key exclusion criteria	1. Fasting plasma glucose greater than 6 mmol/L 2. BMI greater than 26 kg/m^2 3. Psychiatric disorder and/or use of antipsychotic 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 greater than 7 mmol/L and or triglycerides greater than 2 mmol/L 9. Recent weight changes or attempts to lose weight (greater than 3 kg weight gain or loss, within the last three 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 two months) 15. Recent participation in other research projects (within the last three months), participation in two or more projects in one year 16. Extensive sporting activities (more than ten hours of exercise per week)
Date of first enrolment	10/04/2006
Date of final enrolment	26/09/2006

Locations

Countries of recruitment

Netherlands

Study participating centre

Department Endocrinology and Metabolism

Leiden
2300 RC
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/09/2010		Yes	No