Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000911099
Ethics application status
Not yet submitted
Date submitted
26/10/2010
Date registered
26/10/2010
Date last updated
26/10/2010
Type of registration
Prospectively registered

Titles & IDs
Public title
The metabolic effect of antipsychotic medication
Scientific title
The effect of antipyschotic medication in healthy volunteers on glucose metabolism and gut hormones
Secondary ID [1] 252955 0
No other ID number at this stage
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Schizophrenia 258486 0
Glucose intolerance 258487 0
Condition category
Condition code
Mental Health 258654 258654 0 0
Schizophrenia
Metabolic and Endocrine 258655 258655 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
patients will be randomised to one of the four groups:
group 1:
8 days use of olanzapine 10mg daily (oral tablets)

group2:
8 days use of olanzapine 10mg daily (oral tablets) +
metformin oral tablets 1g twice a day during the same 8 day period

group 3:
8 days use of olanzapine 10mg daily (oral tablets) + sitagliptin oral tablets 100mg daily during the same 8 day period

group 4:
8 days use of olanzapine 10mg daily (oral tablets) + exenatide (subcutaneous injection) 10micrograms twice a day during the same 8 day period
Intervention code [1] 257484 0
Treatment: Drugs
Comparator / control treatment
Olanzapine alone without additional treatment
Control group
Active

Outcomes
Primary outcome [1] 259505 0
post-olanzapine change in glucagon-like-peptide-1 (GLP1) and glucagon area under curve during oral glucose tolerance test compared with baseline.
Timepoint [1] 259505 0
testing prior to 8 day treatment of olanzapine +/- one of exenatide, metformin or sitagliptin. testing again after 8 days teatment of treatment.
Secondary outcome [1] 266099 0
post-olanzapine change in glucose and insulin area under curve during oral glucose tolerance test;
Timepoint [1] 266099 0
testing by glucose tolerance test, by hyperinsulinemic euglycemic clamp) prior to 8 day treatment of olanzapine +/- one of exenatide, metformin or sitagliptin. Tests repeat again on 2 occasions after 8 days treatment.
Secondary outcome [2] 266101 0
change in insulin resistance post-olanzapine;
Timepoint [2] 266101 0
testing by glucose tolerance test, by hyperinsulinemic euglycemic clamp) prior to 8 day treatment of olanzapine +/- one of exenatide, metformin or sitagliptin. Tests repeat again on 2 occasions after 8 days treatment.
Secondary outcome [3] 266102 0
effect of rescue drugs (exentatide or metformin or sitagliptin) on olanzapine induced changes in GLP-1, glucagon, glucose and insulin resistance.
Timepoint [3] 266102 0
testing by glucose tolerance test, by hyperinsulinemic euglycemic clamp) prior to 8 day treatment of olanzapine +/- one of exenatide, metformin or sitagliptin. Tests repeat again on 2 occasions after 8 days treatment.

Eligibility
Key inclusion criteria
BMI 20-25
healthy male volunteers
Minimum age
18 Years
Maximum age
40 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
family or personal history of diabetes, schizophrenia.
current regular medications.
smoker

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocating a random number to each subject at enrolment that corresponds to one of the four study groups. Numbers will be concealed in envelopes picked from a box at enrolment by principal investigator.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random number out of a list of number 1-20
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment outside Australia
Country [1] 2999 0
New Zealand
State/province [1] 2999 0

Funding & Sponsors
Funding source category [1] 257933 0
Government body
Name [1] 257933 0
Health Research Council
Country [1] 257933 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Private Bag 92019, Auckland 1142, New Zealand
Country
New Zealand
Secondary sponsor category [1] 257124 0
Individual
Name [1] 257124 0
Dr Rinki Murphy
Address [1] 257124 0
Private Bag 92019, Auckland 1142, New Zealand
Country [1] 257124 0
New Zealand

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 259945 0
Northern X Ethics Committee
Ethics committee address [1] 259945 0
Private Bag 92-522, Wellesley St
Auckland
Ethics committee country [1] 259945 0
New Zealand
Date submitted for ethics approval [1] 259945 0
01/12/2010
Approval date [1] 259945 0
Ethics approval number [1] 259945 0

Summary
Brief summary
Antipsychotic drugs are the second most prescribed medications in New Zealand for the treatment of schizophrenia and other forms of psychosis (Pharmac annual review). Over 40,000 people are prescribed one of the four Pharmac funded second generation antipsychotic drugs (SGAs) clozapine, risperidone, quetiapine or olanzapine, at a cost of $61.6 million NZD annually (Pharmac 2009 annual review). However, the most effective antipsychotic drugs, clozapine and olanzapine, greatly increase the risk of weight gain and type 2 diabetes, and so further increase morbidity, mortality and health care costs. It was previously thought the weight gain was the cause of the type 2 diabetes in these patients but we have recently shown in animal models that these drugs directly impair glucose metabolism. This occurred via suppression of Glucagon-Like-Peptide-1(GLP-1) levels and these defects could be overcome by restoration of GLP-1 signalling. Given the large number of patients on SGA medications it is clearly very important to properly understand how these drugs affect glucose metabolism and what the most appropriate therapies for this are.

We aim to determine whether regulation of the GLP-1/glucagon axis is responsible for the effects SGAs have on glucose metabolism we propose a clinical trial in healthy subjects to test the effect of acute exposure (single dose or 8-day) of olanzapine on glucose tolerance, insulin resistance and hepatic glucose output. We will determine whether this is associated with changes in glucagon and GLP-1 levels (based on the hypothesis developed from our animal data). We will go on to determine whether drug induced impairments in glucose metabolism can best be overcome by restoration of GLP-1 signalling using currently available drugs.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31833 0
Address 31833 0
Country 31833 0
Phone 31833 0
Fax 31833 0
Email 31833 0
Contact person for public queries
Name 15080 0
Shelley Yip
Address 15080 0
Rm 83, Level 12,
Faculty of Medical and Health Sciences
The University of Auckland
Private Bag 92019
Auckland
Country 15080 0
New Zealand
Phone 15080 0
+64 21 1017436 or +64 9 3737599 ext 81768
Fax 15080 0
Email 15080 0
shelleyy@adhb.govt.nz
Contact person for scientific queries
Name 6008 0
Shelley Yip
Address 6008 0
Rm 83, Level 12,
Faculty of Medical and Health Sciences
The University of Auckland
Private Bag 92019
Auckland
Country 6008 0
New Zealand
Phone 6008 0
+64 21 1017436 or +64 9 3737599 ext 81768
Fax 6008 0
Email 6008 0
shelleyy@adhb.govt.nz

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.