Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00205660
Status:
COMPLETED
Last Update Posted:
2019-01-15
First Post:
2005-09-12
Brief Title:
Changes in Adiposity Metabolic Measures From Atypicals to Aripiprazole
Sponsor:
Washington University School of Medicine
Organization:
Washington University School of Medicine
Study Overview
Official Title:
Changes in Adiposity and Metabolic Measures During Medication Switches to Aripiprazole From Other Atypical Antipsychotics
Status:
COMPLETED
Status Verified Date:
2018-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BMS
Brief Summary:
This proposal aims to use well-validated methodologies such as dual energy x-ray absorptiometry DEXA frequently sampled oral glucose tolerance tests fsOGTTs and hyperinsulinemic euglycemic clamps to characterize the metabolic effects of 12 weeks of aripiprazole treatment following chronic pretreatment with olanzapine quetiapine risperidone or ziprasidone
We hypothesize that switching to aripiprazole treatment will induce improvements in total body adiposity inflammation eg high sensitivity C-reactive protein hsCRP glucose metabolism eg insulin sensitivity and lipid metabolism eg fasting plasma triglyceride in comparison to chronic pretreatment with olanzapine risperidone and quetiapine
We hypothesize that switching to aripiprazole treatment will induce improvements in total body adiposity inflammation eg high sensitivity C-reactive protein hsCRP glucose metabolism eg insulin sensitivity and lipid metabolism eg fasting plasma triglyceride in comparison to chronic pretreatment with olanzapine risperidone and quetiapine
Detailed Description:
Schizophrenia is associated with increased rates of obesity hyperglycemia dyslipidemia and type 2 diabetes mellitus T2DM causing increased morbidity and mortality due to acute eg diabetic ketoacidosis and long-term eg vascular disease complications1-5As a result cardiovascular CV mortality remains one of the leading causes of excess mortality in patients with psychotic disorders67 T2DM is characterized by disturbances in insulin secretion and insulin action at skeletal muscle ie decreased glucose disposal liver ie increased glucose production and adipose tissue ie increased lipolysis leading to disturbances in glucose and lipid metabolism The metabolic syndrome of insulin resistance hyperinsulinemia dyslipidemia and abdominal adiposity usually includes a procoagulant state and endothelial dysfunction and is strongly associated with increased CV morbidity and mortality
Hyperglycemia was first noted in patients with schizophrenia prior to the introduction of antipsychotic medications but glucoregulatory defects dyslipidemia and increased adiposity are all additionally associated with both older and newer antipsychotic treatments1 In most patients these metabolic derangements are primarily related to increases in adiposity although treatment effects independent of adiposity may also play a role in up to 25 of cases of new onset T2DM during antipsychotic treatment89 Increased adiposity especially visceral abdominal adiposity is associated with insulin resistance elevated plasma lipids and increases in inflammatory markers All of these conditions contribute to elevated mortality and all can be directly measured in patients treated with different medications
Direct measures of adiposity insulin action and secretion plasma lipid levels and inflammation are available and have been well validated as predictors of CV disease and T2DM complications Unfortunately to date studies using large population-based samples of patients taking antipsychotic medications have only used insensitive measures like random glucose or surrogate measures such as prescription of an oral hypoglycemic agent to estimate the prevalence of T2DM during antipsychotic treatment No data are available concerning insulin sensitivity and secretion plasma lipids or inflammatory markers from large population-based samples of individuals treated with antipsychotic medications Reviewed below limited data are available from smaller analytic studies using sensitive measures Despite convergent evidence for the contribution of adiposity to the metabolic derangements associated with antipsychotic treatment investigators have only begun to use direct measures of adiposity to characterize the weight gain associated with antipsychotic treatment
This proposal aims to use well-validated methodologies such as dual energy x-ray absorptiometry DEXA frequently sampled oral glucose tolerance tests fsOGTTs and hyperinsulinemic euglycemic clamps to characterize the metabolic effects of 12 weeks of aripiprazole treatment following chronic pretreatment with olanzapine quetiapine risperidone or ziprasidone
We hypothesize that switching to aripiprazole treatment will induce improvements in total body adiposity inflammation eg high sensitivity C-reactive protein hsCRP glucose metabolism eg insulin sensitivity and lipid metabolism eg fasting plasma triglyceride in comparison to chronic pretreatment with olanzapine risperidone and quetiapine
Aim 1 To characterize the glucoregulatory effects of 12 weeks of aripiprazole treatment
This study hypothesizes that switching to aripiprazole treatment will be associated with statistically significant improvements in glucose metabolism eg insulin sensitivity in comparison to chronic pretreatment with olanzapine Given the planned sample size and study duration we hypothesize that aripiprazole treatment will be associated with numerical but not statistically significant improvements in comparison to pretreatment with risperidone or quetiapine We hypothesize that aripiprazole treatment will be associated with no significant change in comparison to pretreatment with ziprasidone These hypotheses will be evaluated by measuring insulin sensitivity and other indices via fsOGTTs and hyperinsulinemic euglycemic clamps
Aim 2 To evaluate medication-related measures of abdominal fat total body fat and total fat-free mass
This study hypothesizes that switching to aripiprazole treatment will be associated with reductions in adipose tissue mass in comparison to olanzapine We hypothesize that aripiprazole treatment will be associated with numerical but not statistically significant reductions in comparison to pretreatment with risperidone or quetiapine We hypothesize that aripiprazole treatment will be associated with no change in comparison to pretreatment with ziprasidone These hypotheses will be evaluated by measuring body composition using dual energy x-ray absorptiometry DEXA and anthropomorphic measurements to provide estimates of total body fat abdominal fat and fat-free mass
Hyperglycemia was first noted in patients with schizophrenia prior to the introduction of antipsychotic medications but glucoregulatory defects dyslipidemia and increased adiposity are all additionally associated with both older and newer antipsychotic treatments1 In most patients these metabolic derangements are primarily related to increases in adiposity although treatment effects independent of adiposity may also play a role in up to 25 of cases of new onset T2DM during antipsychotic treatment89 Increased adiposity especially visceral abdominal adiposity is associated with insulin resistance elevated plasma lipids and increases in inflammatory markers All of these conditions contribute to elevated mortality and all can be directly measured in patients treated with different medications
Direct measures of adiposity insulin action and secretion plasma lipid levels and inflammation are available and have been well validated as predictors of CV disease and T2DM complications Unfortunately to date studies using large population-based samples of patients taking antipsychotic medications have only used insensitive measures like random glucose or surrogate measures such as prescription of an oral hypoglycemic agent to estimate the prevalence of T2DM during antipsychotic treatment No data are available concerning insulin sensitivity and secretion plasma lipids or inflammatory markers from large population-based samples of individuals treated with antipsychotic medications Reviewed below limited data are available from smaller analytic studies using sensitive measures Despite convergent evidence for the contribution of adiposity to the metabolic derangements associated with antipsychotic treatment investigators have only begun to use direct measures of adiposity to characterize the weight gain associated with antipsychotic treatment
This proposal aims to use well-validated methodologies such as dual energy x-ray absorptiometry DEXA frequently sampled oral glucose tolerance tests fsOGTTs and hyperinsulinemic euglycemic clamps to characterize the metabolic effects of 12 weeks of aripiprazole treatment following chronic pretreatment with olanzapine quetiapine risperidone or ziprasidone
We hypothesize that switching to aripiprazole treatment will induce improvements in total body adiposity inflammation eg high sensitivity C-reactive protein hsCRP glucose metabolism eg insulin sensitivity and lipid metabolism eg fasting plasma triglyceride in comparison to chronic pretreatment with olanzapine risperidone and quetiapine
Aim 1 To characterize the glucoregulatory effects of 12 weeks of aripiprazole treatment
This study hypothesizes that switching to aripiprazole treatment will be associated with statistically significant improvements in glucose metabolism eg insulin sensitivity in comparison to chronic pretreatment with olanzapine Given the planned sample size and study duration we hypothesize that aripiprazole treatment will be associated with numerical but not statistically significant improvements in comparison to pretreatment with risperidone or quetiapine We hypothesize that aripiprazole treatment will be associated with no significant change in comparison to pretreatment with ziprasidone These hypotheses will be evaluated by measuring insulin sensitivity and other indices via fsOGTTs and hyperinsulinemic euglycemic clamps
Aim 2 To evaluate medication-related measures of abdominal fat total body fat and total fat-free mass
This study hypothesizes that switching to aripiprazole treatment will be associated with reductions in adipose tissue mass in comparison to olanzapine We hypothesize that aripiprazole treatment will be associated with numerical but not statistically significant reductions in comparison to pretreatment with risperidone or quetiapine We hypothesize that aripiprazole treatment will be associated with no change in comparison to pretreatment with ziprasidone These hypotheses will be evaluated by measuring body composition using dual energy x-ray absorptiometry DEXA and anthropomorphic measurements to provide estimates of total body fat abdominal fat and fat-free mass
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None