Clinical trial NCT00287820: Comparative Effects of Chronic Treatment With Olanzapine and Risperidone on Glucose and Lipid Metabolism
Official title: Independent Investigator Grant Study-Comparative Effects of Chronic Treatment With Olanzapine and Risperidone on Glucose and Lipid Metabolism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Diabetes
Metabolic Syndrome
Hyperglycemia
Keywords: schizophrenia
diabetes
metabolic syndrome
hyperglycemia
glucose
insulin
lipids
IL-6
prolactin
Lead sponsor: Nathan Kline Institute for Psychiatric Research
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2006-02-07
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to assess whether chronic treatment with olanzapine over a five-month period produces a significant increase in abnormalities in glucose levels. The main secondary objective is to evaluate whether the increase in glucose levels and rate of glucose abnormalities differs between Olanzapine and Risperidone during this treatment period. Additional secondary objectives of the study are to investigate similar questions with respect to glycohemoglobin, triglycerides and other measures of glucose and lipid metabolism.

We hypothesize that Olanzapine will not be inferior to Risperidone in extent of increase in the primary outcome measure of serum glucose, and secondary measures of glycohemoglobin, insulin and lipids.

Detailed description: In the on-going study in progress we use an extensive battery of assessments to investigate a)fasting levels of glucose and lipids at baseline and monthly during 5 months of treatment, b) glucose tolerance tests to investigate glucose and insulin abnormalities after a glucose load at baseline and during study treatment, and c)the effects of treatment with olanzapine and risperidone of post prandial glucose metabolism after a fatty meal (as detailed in the body of the proposal). Recent studies have shown that increased postprandial lipidemia is an important feature of many patients with type 2 diabetes and atherosclerosis. In addition to the biochemical measures, we will also assess clinical effects (PANSS and CGI ratings) and other side-effects (weight gain, appetite, somnolence, and EPS and TD). The specific plan calls for inpatients in a tertiary care hospital to be randomly assigned to olanzapine or risperidone, using a stratified random assignment procedure, and treated for five months with either olanzapine or risperidone. We estimate that we will have to enroll a sample of approximately 50-55 patients to obtain 46 acceptable complete cases(as specified in proposal below). On the basis of preliminary results from our prior and ongoing studies we predict no significant increase in glucose abnormalities from baseline during chronic treatment with olanzapine and no significant differences in development of glucose abnormalities in patients in patient treated with olanzapine and risperidone.

Additional measures being investigated include: comparison of olanzapine and risperidone in glucose and lipid responses to a fatty meal, ghrelin changes in response to a fatty mean, and CRP and IL-6, and thyroid and prolactin response to five months of treatment with the two drugs.

Eligibility criteria: Inclusion Criteria:

* Diagnosis
* Schizophrenia or schizoaffective psychosis
* 18-65 years of age

Exclusion Criteria:

* Currently being treated with oral antidiabetics or insulin

Primary outcomes:
measure: Serum glucose
timeFrame: during 5 months of treatment compared to baseline
measure: Hb1AC
timeFrame: during 5 months of treatment compared to baseline
measure: triglycerides
timeFrame: during 5 months of treatment compared to baseline
measure: cholesterol
timeFrame: during 5 months of treatment compared to baseline
measure: insulin
timeFrame: during 5 months of treatment compared to baseline
measure: c-peptide
timeFrame: during 5 months of treatment compared to baseline
Secondary outcomes:
measure: ghrelin
timeFrame: during 5 months of treatment compared to baseline
measure: CRP
timeFrame: during 5 months of treatment compared to baseline
measure: Thyroid hormones
timeFrame: during 5 months of treatment compared to baseline
measure: prolactin
timeFrame: during 5 months of treatment compared to baseline
measure: Il-6
timeFrame: during 5 months treatment compared to baseline
measure: PANSS scores
timeFrame: during 5 months of treatment compared to baseline
measure: CGI score
timeFrame: during 5 months of treatment compared to baseline
measure: EPS scores
timeFrame: during 5 months of treatment compared to baseline
measure: TD Scores
timeFrame: during 5 months of treatment compared to baseline
Other outcomes:
Locations:
city: New York
country: United States
facility: Manhattan Psychaitric Center
state: New York
Study officials:
affiliation: NYU Medical School, Dept of Psychiatry and Manhattan Psychiatric Center
name: Robert C Smith, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Smith RC, Rachakonda S, Dwivedi S, Davis JM. Olanzapine and risperidone effects on appetite and ghrelin in chronic schizophrenic patients. Psychiatry Res. 2012 Oct 30;199(3):159-63. doi: 10.1016/j.psychres.2012.03.011. Epub 2012 Apr 3.
citation: Smith RC, Lindenmayer JP, Hu Q, Kelly E, Viviano TF, Cornwell J, Vaidhyanathaswamy S, Marcovina S, Davis JM. Effects of olanzapine and risperidone on lipid metabolism in chronic schizophrenic patients with long-term antipsychotic treatment: a randomized five month study. Schizophr Res. 2010 Jul;120(1-3):204-9. doi: 10.1016/j.schres.2010.04.001. Epub 2010 May 10.
citation: Smith RC, Lindenmayer JP, Davis JM, Kelly E, Viviano TF, Cornwell J, Hu Q, Khan A, Vaidhyanathaswamy S. Effects of olanzapine and risperidone on glucose metabolism and insulin sensitivity in chronic schizophrenic patients with long-term antipsychotic treatment: a randomized 5-month study. J Clin Psychiatry. 2009 Nov;70(11):1501-13. doi: 10.4088/JCP.08m04446yel. Epub 2009 Oct 6.