Condition category
Nutritional, Metabolic, Endocrine
Date applied
11/04/2007
Date assigned
11/04/2007
Last edited
05/11/2010
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr S Vidarsdottir

ORCID ID

Contact details

Department Endocrinology and Metabolism
Leiden University Medical Centre
C4-R
P.O. Box 9600
Leiden
2300 RC
Netherlands
+31 (0)71 526 3082
s.vidarsdottir@lumc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

Study hypothesis

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

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).

Study design

Randomised, active controlled, crossover trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

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 names

Olanzapine standard oral tablets and orally disintegrating tablets

Primary outcome measures

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.

Secondary outcome measures

Physical activity, this was measured for three days between day one and four of the intervention.

Overall trial start date

10/04/2006

Overall trial end date

26/09/2006

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Male

Target number of participants

12

Participant 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)

Recruitment start date

10/04/2006

Recruitment end date

26/09/2006

Locations

Countries of recruitment

Netherlands

Trial participating centre

Department Endocrinology and Metabolism
Leiden
2300 RC
Netherlands

Sponsor information

Organisation

Leiden University Medical Centre (LUMC) (The Netherlands)

Sponsor details

Department of Endocrinology and Metabolism
P.O. Box 9600
Leiden
2300 RC
Netherlands
+31 (0)71 526 3082
h.pijl@lumc.nl

Sponsor type

Hospital/treatment centre

Website

http://www.lumc.nl/english/start_english.html

Funders

Funder type

Industry

Funder name

Eli Lilly (The Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Dutch Diabetes Research Fund (The Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20441717

Publication citations

  1. Results

    Vidarsdottir S, Vlug P, Roelfsema F, Frölich M, Pijl H, Orally disintegrating and oral standard olanzapine tablets similarly elevate the homeostasis model assessment of insulin resistance index and plasma triglyceride levels in 12 healthy men: a randomized crossover study., J Clin Psychiatry, 2010, 71, 9, 1205-1211, doi: 10.4088/JCP.08m04654yel.

Additional files

Editorial Notes