Ignite Creation Date:
2024-05-05 @ 11:37 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00094796
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2004-10-22
Brief Title:
Rosiglitazone to Reverse Metabolic Defects in Diabetes
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Evaluation of Rosiglitazone in Reversing Metabolic Defects of Pre-Diabetes and Type 2 Diabetes Mellitus
Status:
COMPLETED
Status Verified Date:
2008-09-03
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:
None
Brief Summary:
This study will examine whether the anti-diabetes medicine rosiglitazone can safely and effectively reverse the early problems of type 2 diabetes and delay the onset of disease in people with pre-diabetes The underlying problem in people with diabetes or pre-diabetes is insulin resistance lowered sensitivity to insulin resulting in poor glucose sugar regulation Rosiglitazone improves the bodys sensitivity to insulin
Patients 21 years of age and older who have type 2 diabetes or who are pre-diabetic glucose intolerantinsulin resistant may be eligible for this study Candidates are screened with a medical history physical examination blood tests echocardiography heart ultrasound exercise test brachial artery reactivity test see below and possibly a muscle biopsy
Participants take one rosiglitazone tablet daily by mouth for 2 weeks The dose is then increased to two tablets daily for another 2 weeks and then to 4 tablets daily for the remainder of the 12-week treatment period In addition to treatment patients undergo the following tests and procedures
Resting and exercise metabolic testing The amount of oxygen taken in and carbon dioxide exhaled during breathing is measured while the patient rests in a chair and then while he or she exercises on a stationary bicycle or treadmill Both at rest and during exercise the patient wears a facemask that measures the amount of oxygen used During exercise heart rate is monitored with electrodes on the chest arms and thighs The exercise test is repeated three times once to become familiar with the test again the next day to measure exercise capacity and again 3 days later The third test is less strenuous and is optional
Muscle biopsy optional A small area of skin over a calf muscle is numbed with a local anesthetic and a 1-inch incision is made over the muscle A small amount of muscle tissue is taken and the incision is closed with stitches
Brachial reactivity study This ultrasound study tests how well the patients arteries widen The subject rests on a bed for 30 minutes An ultrasound measuring device is placed over the artery just above the elbow The size of the artery and blood flow through it are measured before and after inflating a pressure cuff around the forearm The pressure cuff stops the flow of blood to the arm for a few minutes After a 15-minute rest a nitroglycerin tablet medicine that causes blood vessels to relax is placed under the patients tongue Before and 3 minutes after the nitroglycerin is given the size of the artery and blood flow through it are measured again
Blood samples Blood samples are collected at the beginning and end of the study and at study visits in between
Study visits Patients come to the Clinical Center biweekly or monthly for a follow-up history physical examination and blood tests At the end of the3-month treatment period they receive recommendations about possible treatment modifications to best maintain glucose tolerance Their physicians are informed of how their blood sugar was controlled Six months after completing the study patients undergo a final study evaluation and blood tests and are then invited to return for yearly checkups after that
Patients 21 years of age and older who have type 2 diabetes or who are pre-diabetic glucose intolerantinsulin resistant may be eligible for this study Candidates are screened with a medical history physical examination blood tests echocardiography heart ultrasound exercise test brachial artery reactivity test see below and possibly a muscle biopsy
Participants take one rosiglitazone tablet daily by mouth for 2 weeks The dose is then increased to two tablets daily for another 2 weeks and then to 4 tablets daily for the remainder of the 12-week treatment period In addition to treatment patients undergo the following tests and procedures
Resting and exercise metabolic testing The amount of oxygen taken in and carbon dioxide exhaled during breathing is measured while the patient rests in a chair and then while he or she exercises on a stationary bicycle or treadmill Both at rest and during exercise the patient wears a facemask that measures the amount of oxygen used During exercise heart rate is monitored with electrodes on the chest arms and thighs The exercise test is repeated three times once to become familiar with the test again the next day to measure exercise capacity and again 3 days later The third test is less strenuous and is optional
Muscle biopsy optional A small area of skin over a calf muscle is numbed with a local anesthetic and a 1-inch incision is made over the muscle A small amount of muscle tissue is taken and the incision is closed with stitches
Brachial reactivity study This ultrasound study tests how well the patients arteries widen The subject rests on a bed for 30 minutes An ultrasound measuring device is placed over the artery just above the elbow The size of the artery and blood flow through it are measured before and after inflating a pressure cuff around the forearm The pressure cuff stops the flow of blood to the arm for a few minutes After a 15-minute rest a nitroglycerin tablet medicine that causes blood vessels to relax is placed under the patients tongue Before and 3 minutes after the nitroglycerin is given the size of the artery and blood flow through it are measured again
Blood samples Blood samples are collected at the beginning and end of the study and at study visits in between
Study visits Patients come to the Clinical Center biweekly or monthly for a follow-up history physical examination and blood tests At the end of the3-month treatment period they receive recommendations about possible treatment modifications to best maintain glucose tolerance Their physicians are informed of how their blood sugar was controlled Six months after completing the study patients undergo a final study evaluation and blood tests and are then invited to return for yearly checkups after that
Detailed Description:
The majority of insulin resistant individuals predominantly individuals with type 2 diabetes - T2DM develop a disproportionate incidence of cardiovascular disease burden including hypertension coronary artery disease peripheral vascular disease and heart failure The underlying pathophysiology is multifactorial but is primarily driven by insulin-resistance mediated regulatory events These include augmented oxidative stress upregulation of pro-inflammatory and anti-thrombotic signaling pathways detrimental effects of advanced glycosylation end-products and perturbations in lipid and fatty acid metabolism Evidence is emerging to support a role of perturbed mitochondrial respiratory regulation and subsequent endothelial dysfunction as early events in the insulin-resistance syndrome These in turn are proposed to result in the subsequent development of the cardiovascular clinical sequelae
In the last few years pharmacologic compounds have been developed that directly modulate insulin resistancesensitivity Activation of the peroxisome proliferator-activated receptor PPAR family of transcription factors has been shown to augment insulin sensitivity Agents that activate numerous PPAR family members ie pan-PPAR agonists and PPAR gamma PPAR gamma specific agonists promote improved insulin sensitivity Whether these compounds modify the underlying mitochondrial and endothelial pathophysiology with the potential of preventing progression of cardiovascular disease in insulin-resistant subjects has not been systematically investigated
The hypothesis intrinsic to this proposal is that PPAR activation will improve mitochondrial respiratory and endothelial cell function in parallel with improved insulin sensitization in insulin-resistant and T2DM subjects The primary objective of this study is to establish the effects of the PPAR gamma agonist rosiglitazone on exercise-modulated cardiopulmonary-metabolic function functional measures of mitochrondrial respiratory function in insulin resistant and T2DM subjects that are either naive to hypoglycemic therapy or are on current therapy with other established classes on anti-diabetic agents with or without associated cardiovascular disease As secondary end points we will evaluate numerous biological assays of skeletal muscle mitochondrial function endothelial function and changes in parameters of insulin sensitivity These include 1 skeletal muscle mitochondrial respiration 2 skeletal muscle expression profiles of genes encoding mitochondrial biogenesis program and mitochondrial respiratory control 3 brachial artery reactivity 4 endothelial progenitor cell number and colony-forming capacity 5 monocyte gene expression profiling to evaluate insulin and inflammatory-mediator regulatory events and 6 serological evaluation in change in insulin sensitivity and inflammation The study is designed as a phase II clinical trial where subjects will receive rosiglitazone for three months duration Baseline and 3 month laboratory studies will include 1 rest and exercise cardiopulmonary metabolic testing 2 skeletal muscle biopsy for mitochondrial function and gene expression profiling analysis 3 brachial artery reactivity testing and 4 serological and blood cell sampling to determine biochemical cellular and genomic perturbations in response to insulin-sensitization therapy in this cohort
In the last few years pharmacologic compounds have been developed that directly modulate insulin resistancesensitivity Activation of the peroxisome proliferator-activated receptor PPAR family of transcription factors has been shown to augment insulin sensitivity Agents that activate numerous PPAR family members ie pan-PPAR agonists and PPAR gamma PPAR gamma specific agonists promote improved insulin sensitivity Whether these compounds modify the underlying mitochondrial and endothelial pathophysiology with the potential of preventing progression of cardiovascular disease in insulin-resistant subjects has not been systematically investigated
The hypothesis intrinsic to this proposal is that PPAR activation will improve mitochondrial respiratory and endothelial cell function in parallel with improved insulin sensitization in insulin-resistant and T2DM subjects The primary objective of this study is to establish the effects of the PPAR gamma agonist rosiglitazone on exercise-modulated cardiopulmonary-metabolic function functional measures of mitochrondrial respiratory function in insulin resistant and T2DM subjects that are either naive to hypoglycemic therapy or are on current therapy with other established classes on anti-diabetic agents with or without associated cardiovascular disease As secondary end points we will evaluate numerous biological assays of skeletal muscle mitochondrial function endothelial function and changes in parameters of insulin sensitivity These include 1 skeletal muscle mitochondrial respiration 2 skeletal muscle expression profiles of genes encoding mitochondrial biogenesis program and mitochondrial respiratory control 3 brachial artery reactivity 4 endothelial progenitor cell number and colony-forming capacity 5 monocyte gene expression profiling to evaluate insulin and inflammatory-mediator regulatory events and 6 serological evaluation in change in insulin sensitivity and inflammation The study is designed as a phase II clinical trial where subjects will receive rosiglitazone for three months duration Baseline and 3 month laboratory studies will include 1 rest and exercise cardiopulmonary metabolic testing 2 skeletal muscle biopsy for mitochondrial function and gene expression profiling analysis 3 brachial artery reactivity testing and 4 serological and blood cell sampling to determine biochemical cellular and genomic perturbations in response to insulin-sensitization therapy in this cohort
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 |
|---|---|---|---|
| 05-H-0009 | None | None | None |