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Sponsors and Collaborators: |
University of Washington Seattle Institute for Biomedical and Clinical Research GlaxoSmithKline |
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Information provided by: | University of Washington |
ClinicalTrials.gov Identifier: | NCT00194896 |
The purpose of this research is to test whether one treatment is superior over another in the management of type 1.5 diabetes. Specifically we are testing recently diagnosed antibody positive type 2 diabetic patients to determine whether treatment with rosiglitazone results in greater preservation of beta cell function compared to treatment with glyburide.
Condition | Intervention |
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Type 2 Diabetes Mellitus |
Drug: rosiglitazone Drug: glyburide |
Study Type: | Interventional |
Study Design: | Active Control, Efficacy Study, Open Label, Parallel Assignment, Randomized, Treatment |
Official Title: | Rosiglitazone Intervention Study in Patients With Type 1-1/2 Diabetes |
Enrollment: | 65 |
Study Start Date: | February 2000 |
Estimated Study Completion Date: | December 2008 |
Estimated Primary Completion Date: | September 2008 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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rosiglitazone: Active Comparator
Rosiglitazone is an oral antidiabetic agent which acts primarily by increasing insulin sensitivity. The rosiglitazone treatment group will commence therapy with 4 mg once per day and increase to twice per day if adequate glycemic control is not achieved.
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Drug: rosiglitazone
Tablet taken orally at a dosage of 4 mg once per day and increase to twice per day if adequate glycemic control is not achieved. Study drug will be taken up to 3 years.
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glyburide: Active Comparator
Glyburide is a sulfonylurea. Glyburide therapy will be initiated with 2.5 mg in the morning or the patient will be maintained on the dose they had been receiving prior to starting the study. This starting dose will be raised by 2.5 in the evening and further up to a maximum of 10 mg twice a day if necessary to achieve desired glycemic control.
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Drug: glyburide
Tablet taken orally, initially 2.5 mg in the morning or dose subject received prior to starting the study. Dosage will be increased by 2.5 mg in the evening up to a maximum of 10 mg twice a day if necessary to achieve desired glycemic control. Study drug will be taken up to 3 years.
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Type 1 diabetes and Type 2 diabetes have different underlying pathophysiologic processes. The disease process in classical Type 1 diabetes is an autoimmune destruction of the pancreatic beta cells. In contrast, the disease process in classical Type 2 diabetes is not autoimmune in nature, a decreased sensitivity to insulin action is central to the disease process, and a poorly understood but non-inflammatory beta cell lesion occurs which diminishes insulin secretion. In clinical practice, the diagnosis of Type 1 versus Type 2 diabetes is made phenotypically using variables such as age at onset, apparent abruptness of onset of hyperglycemia, presence of ketosis, degree of obesity (especially central and intra abdominal), prevalence of other autoimmune diseases, and apparent need for insulin replacement. This clinical distinction of Type 1 versus Type 2 diabetes is recognized to be imperfect.
There is also a third group of individuals, who phenotypically are usually like classic Type 2 diabetics but who are positive for one or more of the autoantibodies commonly seen in the Type 1 disease process, namely islet cell antibodies (ICA) and/or insulin autoantibodies (IAA) and/or autoantibodies to glutamic acid decarboxylase (GAD Ab) and/or autoantibodies to the tyrosine phosphatase IA 2 (IA 2 Ab). These patients, Ab(+) Type 2 or Type 1.5 diabetes, are the focus of our study. Compared to antibody negative Type 2 diabetics, patients with Type 1.5 diabetes have a more rapid decline in beta cell function, fail sulfonylurea therapy and require insulin therapy earlier (4-13).
Hypothesis: Rosiglitazone treatment will ameliorate or slow the underlying disease process in antibody positive Type 2 diabetes.
Patients meeting the inclusion criteria will come in for a baseline visit. The nature of the study will be explained and informed consent obtained. A fasting blood sample will be obtained for autoantibodies, glucose, C-peptide, HbA1c, genetic typing, and T cell responses to islet antigens. The beta cell function test will be performed. Patients will then be randomized to either rosiglitazone or glyburide.
All patients will be encouraged to perform self blood glucose monitoring twice per day, before breakfast and before dinner. The treatment goals for all patients will be the same: before breakfast and before dinner blood sugar levels between 90-130 mg/dI and HbA1c of less then 7% without severe hypoglycemia. Patients unable to reach goal with monotherapy will have metformin (initially) or acarbose (secondarily) added, as there is no evidence to suggest that either affect beta-cell function.
The rosiglitazone treatment group will commence therapy with 4 mg once per day and increase to twice per day if adequate glycemic control is not achieved. For glyburide, therapy will be initiated with 2.5 mg in the morning or the patient will be maintained on the dose they had been receiving prior to starting the study. This starting dose will be raised by 2.5 mg in the evening and further up to a maximum of 10 mg twice a day if necessary to achieve desired glycemic control.
If adequate control, HbA1c less than 7%, is not achieved on glyburide or rosiglitazone monotherapy, metformin will be added and the dose gradually increased as needed and tolerated to a maximum of 1000 mg twice daily. If necessary, acarbose will also be used up to a maximum dose of 100 mg thrice daily as needed and tolerated.
After initiation of the study, patients will be seen at 1 month and then every 3 months for up to 3 years. Those patients randomized to rosiglitazone will have the liver enzyme ALT monitored every 2 months. In addition, telephone contact may be utilized to achieve and maintain glycemic goals. Each participant will be followed for up to 3 years. Drs. Chiu and Palmer will coordinate the study. If the patient and his/her private physician prefer, the treatment protocol can be implemented by the patient's private physician.
Ages Eligible for Study: | 35 Years to 69 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, Washington | |
DVA Puget Sound Health Care System | |
Seattle, Washington, United States, 98108 |
Principal Investigator: | Jerry P Palmer, MD | Seattle Institute for Biomedical & Clinical Research, University of Washington, DVA Puget Sound Health Care System |
Responsible Party: | University of Washington, Seattle Institute for Biomedical & Clinical Research ( Jerry P. Palmer, MD, Professor, Principal Investigator ) |
Study ID Numbers: | 99-2202-V09, 496539-188 |
Study First Received: | September 14, 2005 |
Last Updated: | February 14, 2008 |
ClinicalTrials.gov Identifier: | NCT00194896 History of Changes |
Health Authority: | United States: Institutional Review Board |
autoantibodies c-peptide glyburide islet proteins |
islet proteins rosiglitazone type 2 diabetes mellitus |
Glyburide Hypoglycemic Agents Metabolic Diseases Autoantibodies Diabetes Mellitus, Type 2 Diabetes Mellitus |
Endocrine System Diseases Endocrinopathy Glucose Metabolism Disorders Rosiglitazone Metabolic Disorder |
Glyburide Hypoglycemic Agents Metabolic Diseases Physiological Effects of Drugs Diabetes Mellitus, Type 2 |
Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Rosiglitazone Pharmacologic Actions |