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Preferred Treatment of Type 1.5 Diabetes

Primary Purpose

Type 2 Diabetes Mellitus

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
rosiglitazone
glyburide
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring type 2 diabetes mellitus, autoantibodies, islet proteins, rosiglitazone, glyburide, c-peptide

Eligibility Criteria

35 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age at onset of diabetes - 35-69 years old. No history of ketonuria or ketoacidosis. Not requiring insulin to achieve glycemic control. Not receiving more than two oral hypoglycemic agents. Not taking a thiazolidinedione agent. HbA1c in established patients (on an oral hypoglycemia agent for over 4 months) of greater than 6% and under 10%. Fasting c-peptide greater than or equal to 0.8 ng/ml. Women must be either post-menopausal or on adequate birth control (i.e. oral contraceptives, tubal ligation, hysterectomy, condoms, or diaphragm) or use abstinence. Exclusion Criteria: Patients with history of chronic pancreatitis or other secondary causes of diabetes. Patients receiving systemic corticosteroids. Patients with severe systemic illness (e.g. recent MI, CHF or cerebral vascular disease). Creatinine greater than 1.4 or liver enzymes greater than 2 times the upper limits of normal. Not able to adhere to the protocol.

Sites / Locations

  • DVA Puget Sound Health Care System

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

rosiglitazone

glyburide

Arm Description

Rosiglitazone is an oral antidiabetic agent which acts primarily by increasing insulin sensitivity. The rosiglitazone treatment group commenced therapy with 4 mg once per day and increase to twice per day if adequate glycemic control was not achieved.

Glyburide is a sulfonylurea. Glyburide therapy was initiated with 2.5 mg in the morning or the patient was maintained on the dose they had been receiving prior to starting the study. This starting dose was 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.

Outcomes

Primary Outcome Measures

Changes in Beta Cell Function Assessed by Fasting and Stimulated C-peptide Measured at 36 Months.
Changes in beta cell function assessed by fasting and stimulated C-peptide measured at 36 months.

Secondary Outcome Measures

Patients Positive for T Cell Responses to Islet Proteins at 36 Months.
Number of participants positive for T cell reactivity to islet proteins at 36 months.

Full Information

First Posted
September 14, 2005
Last Updated
March 27, 2018
Sponsor
University of Washington
Collaborators
Seattle Institute for Biomedical and Clinical Research, GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00194896
Brief Title
Preferred Treatment of Type 1.5 Diabetes
Official Title
Rosiglitazone Intervention Study in Patients With Type 1.5 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
February 2000 (undefined)
Primary Completion Date
September 2008 (Actual)
Study Completion Date
December 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Washington
Collaborators
Seattle Institute for Biomedical and Clinical Research, GlaxoSmithKline

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this research was to test whether one treatment was superior over another in the management of type 1.5 diabetes. Specifically we tested 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.
Detailed Description
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 islet cell autoantibody 512 (IA 2 Ab). These patients, autoantibody positive [Ab(+)] Type 2 or Type 1.5 diabetes, were 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 came in for a baseline visit. The nature of the study was explained and informed consent obtained. A fasting blood sample was obtained for autoantibodies, glucose, C peptide of proinsulin molecule (C-peptide), glycosylated hemoglobin (HbA1c), genetic typing, and T lymphocyte (T cell) responses to islet antigens. The beta cell function test was performed. Patients were then randomized to either rosiglitazone or glyburide. All patients were encouraged to perform self blood glucose monitoring twice per day, before breakfast and before dinner. The treatment goals for all patients was the same: before breakfast and before dinner blood sugar levels between 90-130 milligrams per deciliter (mg/dI) and HbA1c of less then 7% without severe hypoglycemia. Patients unable to reach goal with monotherapy had metformin (initially) or acarbose (secondarily) added, as there is no evidence to suggest that either affect beta-cell function. The rosiglitazone treatment group commenced therapy with 4 milligram (mg) once per day and increased to twice per day if adequate glycemic control was not achieved. For glyburide, therapy was initiated with 2.5 mg in the morning or the patient was maintained on the dose they had been receiving prior to starting the study. The starting dose was 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%, was not achieved on glyburide or rosiglitazone monotherapy, metformin was added and the dose gradually increased as needed and tolerated to a maximum of 1000 mg twice daily. If necessary, acarbose was also used up to a maximum dose of 100 mg thrice daily as needed and tolerated. After initiation of the study, patients were seen at 1 month and then every 3 months for up to 3 years. Those patients randomized to rosiglitazone had the liver enzyme alanine transaminase (ALT) monitored every 2 months. In addition, telephone contact was utilized to achieve and maintain glycemic goals. Each participant was followed for up to 3 years. Drs. Chiu and Palmer coordinated the study. If the patient and his/her private physician prefer, the treatment protocol was implemented by the patient's private physician.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
Keywords
type 2 diabetes mellitus, autoantibodies, islet proteins, rosiglitazone, glyburide, c-peptide

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
64 (Actual)

8. Arms, Groups, and Interventions

Arm Title
rosiglitazone
Arm Type
Active Comparator
Arm Description
Rosiglitazone is an oral antidiabetic agent which acts primarily by increasing insulin sensitivity. The rosiglitazone treatment group commenced therapy with 4 mg once per day and increase to twice per day if adequate glycemic control was not achieved.
Arm Title
glyburide
Arm Type
Active Comparator
Arm Description
Glyburide is a sulfonylurea. Glyburide therapy was initiated with 2.5 mg in the morning or the patient was maintained on the dose they had been receiving prior to starting the study. This starting dose was 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.
Intervention Type
Drug
Intervention Name(s)
rosiglitazone
Other Intervention Name(s)
Avandia
Intervention Description
Tablet taken orally at a dosage of 4 mg once per day and increase to twice per day if adequate glycemic control was not achieved. Study drug was taken up to 3 years.
Intervention Type
Drug
Intervention Name(s)
glyburide
Intervention Description
Tablet taken orally, initially 2.5 mg in the morning or dose subject received prior to starting the study. Dosage was 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 was taken up to 3 years.
Primary Outcome Measure Information:
Title
Changes in Beta Cell Function Assessed by Fasting and Stimulated C-peptide Measured at 36 Months.
Description
Changes in beta cell function assessed by fasting and stimulated C-peptide measured at 36 months.
Time Frame
36 months
Secondary Outcome Measure Information:
Title
Patients Positive for T Cell Responses to Islet Proteins at 36 Months.
Description
Number of participants positive for T cell reactivity to islet proteins at 36 months.
Time Frame
36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age at onset of diabetes - 35-69 years old. No history of ketonuria or ketoacidosis. Not requiring insulin to achieve glycemic control. Not receiving more than two oral hypoglycemic agents. Not taking a thiazolidinedione agent. HbA1c in established patients (on an oral hypoglycemia agent for over 4 months) of greater than 6% and under 10%. Fasting c-peptide greater than or equal to 0.8 ng/ml. Women must be either post-menopausal or on adequate birth control (i.e. oral contraceptives, tubal ligation, hysterectomy, condoms, or diaphragm) or use abstinence. Exclusion Criteria: Patients with history of chronic pancreatitis or other secondary causes of diabetes. Patients receiving systemic corticosteroids. Patients with severe systemic illness (e.g. recent MI, CHF or cerebral vascular disease). Creatinine greater than 1.4 or liver enzymes greater than 2 times the upper limits of normal. Not able to adhere to the protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jerry P Palmer, MD
Organizational Affiliation
Seattle Institute for Biomedical & Clinical Research, University of Washington, DVA Puget Sound Health Care System
Official's Role
Principal Investigator
Facility Information:
Facility Name
DVA Puget Sound Health Care System
City
Seattle
State/Province
Washington
ZIP/Postal Code
98108
Country
United States

12. IPD Sharing Statement

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Preferred Treatment of Type 1.5 Diabetes

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