Ignite Creation Date:
2024-05-05 @ 12:02 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00225225
Status:
TERMINATED
Last Update Posted:
2016-10-20
First Post:
2005-09-21
Brief Title:
Rosiglitazone-Induced Weight Gain
Sponsor:
Stanford University
Organization:
Stanford University
Study Overview
Official Title:
Rosiglitazone-Induced Weight Gain
Status:
TERMINATED
Status Verified Date:
2016-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
due to published data on Rosiglitazone
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Given the high prevalence of type 2 diabetes and the 2- to 4-fold increased risk of fatal and non-fatal coronary heart disease events in these patients long-term glycemic control is of great importance TZDs improves glycemic control in patients with type 2 DM as well as enhances their insulin-mediated glucose disposal However the improvement of glycemic control seen with TZDs may be blunted in the long run by weight gain
Previous data on weight gain during TZD therapy in patients with type 2 DM is very sparse It is generally assumed that an increase in adipocyte differentiation is the cause of weight gain in association with TZD treatment which may limit their use Increased body weight assumed to compromise the positive effects of treatment There is also a theoretical concern that with the development of new adipocytes future weight loss may be difficult
However if weight gain is primarily due to failure to adjust caloric intake in proportion to the decrease in urinary glucose loss it is totally preventable It has been previously shown that improvement of glycemia favored weight gain by decreasing the energy loss in the urine as glucose Severity of weight gain appears to be proportional to the level of glycemic control achieved
The overall goal of the proposed research is to provide the experimental evidence for the later alternative by showing that the modest weight gain that takes place in association with effective rosiglitazone treatment of hyperglycemic patients with type 2 DM is primarily due to its therapeutic efficacy More specifically by decreasing the caloric intake in proportion to a decrease in urinary glucose loss associated with improved glycemic control we will be able to prevent significant weight gain following Rosiglitazone treatment In order to provide an optimal dietary modification that can be universally applied to TZD-treated patients in clinical practice we will have a group with a fixed amount of caloric restriction per day It will be the first randomized controlled trial of a potential strategy for prevention of weight gain associated with thiazolidinediones
Previous data on weight gain during TZD therapy in patients with type 2 DM is very sparse It is generally assumed that an increase in adipocyte differentiation is the cause of weight gain in association with TZD treatment which may limit their use Increased body weight assumed to compromise the positive effects of treatment There is also a theoretical concern that with the development of new adipocytes future weight loss may be difficult
However if weight gain is primarily due to failure to adjust caloric intake in proportion to the decrease in urinary glucose loss it is totally preventable It has been previously shown that improvement of glycemia favored weight gain by decreasing the energy loss in the urine as glucose Severity of weight gain appears to be proportional to the level of glycemic control achieved
The overall goal of the proposed research is to provide the experimental evidence for the later alternative by showing that the modest weight gain that takes place in association with effective rosiglitazone treatment of hyperglycemic patients with type 2 DM is primarily due to its therapeutic efficacy More specifically by decreasing the caloric intake in proportion to a decrease in urinary glucose loss associated with improved glycemic control we will be able to prevent significant weight gain following Rosiglitazone treatment In order to provide an optimal dietary modification that can be universally applied to TZD-treated patients in clinical practice we will have a group with a fixed amount of caloric restriction per day It will be the first randomized controlled trial of a potential strategy for prevention of weight gain associated with thiazolidinediones
Detailed Description:
Study Design Randomized controlled trial Volunteers for the study will be recruited by advertisements in the local newspapers as well as through Stanford University e-mail All studies will occur at Stanford General Clinical Research Center GCRC
At baseline enrolled candidates will be required to keep a daily food and beverage record for 2 weeks as well as blood sugar log of at least 2 measurements a day fasting and pre-dinner Candidates will have an initial nutritiondiabetes consult with dietitian They also will be asked to do a 24-hour urine collection once a week 2 times during the 2 week period for quantitative assessment of glucosuria During those 2 weeks individuals will come for GCRC outpatient visit once a week for weight blood pressure and blood sugar check
After the initial two weeks all individuals will undergo a meal profile test after a 12-hour overnight fast which consists of measurement of daylong plasma glucose free fatty acids and insulin responses to standard meals Food for the test will be prepared by GCRC Metabolic kitchen In order to assess the degree of postprandial and day-long hyperinsulinemia and the benefits of rosiglitazone on the metabolic abnormalities in patients with poor glycemic control we plan to measure plasma glucose free fatty acids and insulin concentrations before 8 am and at hourly intervals for four hours after breakfast at 8 am and four hours after lunch at noon in response to identical test meals containing as percentage of calories 15 protein 40 fat and 45 carbohydrate Baseline blood samples for fasting lipid and lipoprotein concentrations will be obtained after an overnight fast on the day of the meal profile Cholesterol and lipoprotein subclasses will be analyzed by VAP-II method which is based on continuous enzymatic analysis of cholesterol and lipoprotein classes separated by a single vertical spin centrifugation using a controlled-dispersion flow analyzer Hemoglobin A1C will be measured by an affinity chromography assay at baseline and at the end of the study
Randomization protocol After completion of the Meal Profile test all subjects will be started on Rosiglitazone for improvement of their glycemic control and randomized to one of the three groups 15 subjects in each group
1 Continuation of the current diet
2 Reduced calorie diet Amount of reduced calories will be calculated proportionally to the calories lost via glucosuria
3 Fixed calorie reduction diet Reduction of daily caloric intake by 500 kcal Rosiglitazone will be given at 4 mg for the first 4 weeks and if tolerated increased to 8 mg for the duration of the study All candidates will have counseling on general meal plan with the nutritionist
Follow-up Subjects will be followed for 4 months They will come to the GCRC twice a month for weight blood pressure blood sugar checks and for nutrition follow-up
End of the study measurements and clinical procedures meal profile lipid panel 24-hour urine collection will be done at the end of 4 month follow-up period Liver function tests will be done at the baseline 4 8 12 and 16 weeks while on Rosiglitazone
Outcomes we expect to demonstrate at the end of the study that modification of the diet prevents weight gain in Rosiglitazone treated patients and to offer the optimal dietary interventions that could be applied in TZD-treated patients to minimize weight gain while effectively treating DM and insulin resistance
Inclusion Exclusion Inclusion criteria 1 age between 30 and 70 years old 2 normal chemical screening battery 2 BMI less than 36 kgM2 3 non-controlled type 2 DM defined by a fasting plasma glucose between 160 and 220 mgdl 4 individuals should be on a stable dose of sulfonylurea for at least one month prior to the enrollment
Exclusion criteria 1 liver enzymes 25 times above normal values 2 chronic inflammatory neoplastic disease 3 subjects with clinical evidence of congestive heart failure
At baseline enrolled candidates will be required to keep a daily food and beverage record for 2 weeks as well as blood sugar log of at least 2 measurements a day fasting and pre-dinner Candidates will have an initial nutritiondiabetes consult with dietitian They also will be asked to do a 24-hour urine collection once a week 2 times during the 2 week period for quantitative assessment of glucosuria During those 2 weeks individuals will come for GCRC outpatient visit once a week for weight blood pressure and blood sugar check
After the initial two weeks all individuals will undergo a meal profile test after a 12-hour overnight fast which consists of measurement of daylong plasma glucose free fatty acids and insulin responses to standard meals Food for the test will be prepared by GCRC Metabolic kitchen In order to assess the degree of postprandial and day-long hyperinsulinemia and the benefits of rosiglitazone on the metabolic abnormalities in patients with poor glycemic control we plan to measure plasma glucose free fatty acids and insulin concentrations before 8 am and at hourly intervals for four hours after breakfast at 8 am and four hours after lunch at noon in response to identical test meals containing as percentage of calories 15 protein 40 fat and 45 carbohydrate Baseline blood samples for fasting lipid and lipoprotein concentrations will be obtained after an overnight fast on the day of the meal profile Cholesterol and lipoprotein subclasses will be analyzed by VAP-II method which is based on continuous enzymatic analysis of cholesterol and lipoprotein classes separated by a single vertical spin centrifugation using a controlled-dispersion flow analyzer Hemoglobin A1C will be measured by an affinity chromography assay at baseline and at the end of the study
Randomization protocol After completion of the Meal Profile test all subjects will be started on Rosiglitazone for improvement of their glycemic control and randomized to one of the three groups 15 subjects in each group
1 Continuation of the current diet
2 Reduced calorie diet Amount of reduced calories will be calculated proportionally to the calories lost via glucosuria
3 Fixed calorie reduction diet Reduction of daily caloric intake by 500 kcal Rosiglitazone will be given at 4 mg for the first 4 weeks and if tolerated increased to 8 mg for the duration of the study All candidates will have counseling on general meal plan with the nutritionist
Follow-up Subjects will be followed for 4 months They will come to the GCRC twice a month for weight blood pressure blood sugar checks and for nutrition follow-up
End of the study measurements and clinical procedures meal profile lipid panel 24-hour urine collection will be done at the end of 4 month follow-up period Liver function tests will be done at the baseline 4 8 12 and 16 weeks while on Rosiglitazone
Outcomes we expect to demonstrate at the end of the study that modification of the diet prevents weight gain in Rosiglitazone treated patients and to offer the optimal dietary interventions that could be applied in TZD-treated patients to minimize weight gain while effectively treating DM and insulin resistance
Inclusion Exclusion Inclusion criteria 1 age between 30 and 70 years old 2 normal chemical screening battery 2 BMI less than 36 kgM2 3 non-controlled type 2 DM defined by a fasting plasma glucose between 160 and 220 mgdl 4 individuals should be on a stable dose of sulfonylurea for at least one month prior to the enrollment
Exclusion criteria 1 liver enzymes 25 times above normal values 2 chronic inflammatory neoplastic disease 3 subjects with clinical evidence of congestive heart failure
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| SPO 34216 | None | None | None |