The VA Diabetes Trial Follow-up Study (VADT-FS)

Study Overview
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Brief Summary
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CSP #465, Glycemic Control and Complications in Diabetes Mellitus Type 2, was a randomized unblinded clinical trial comparing tight glycemic control to standard glycemic control. Tight glycemic control consisted of giving patients appropriate diabetic medications to lower the patient's HbA1c to around 7%, whereas standard control attempted to lower the patient's HbA1c to between 8% and 9%. The study was conducted at 20 VA medical centers. 1791 patients were randomized over the 2 year accrual period and then followed for an additional 5 years. Follow-up averaged between 5 and 7 years depending upon when the patient was enrolled in the study. Patients were seen on average every three months in the VA Outpatient Clinics. High blood pressure and elevated cholesterol were aggressively treated in patients in both treatment arms. Education regarding diet, exercise, smoking cessation and management of very high and very low glucose was also provided. Data were collected throughout the study on the patients' physical status, adverse and serious adverse events, concomitant medications, and study end points including mortality, heart attack, stroke and surgery to fix the arteries in the heart, legs or neck. The study consisted of broad use of all anti-diabetic treatments commercially available between 2000 and 2008 including oral medications and insulin. Study required medications and all study clinic visits were provided free of the usual VA co-pay. Active clinical follow-up of the sample ended on May 31, 2008. With the end of the clinical trial the patients were transitioned back to usual patient care services, treatment regimens were adjusted where appropriate and future treatment will be dictated by the patient's health and his/her health care provider. It is important to clarify that with the completion of the active clinical trial and transitioning of patients to this observational trial, all responsibility for the care, treatment and oversight of the study patients will become the responsibility of the patients' Primary Care Physician. The Long Term Follow-up will not collect adverse or serious adverse events, or actively treat or have any hands-on care responsibility for the study participants. The proposed Long Term Follow-up Study will consist of centralized computer database searches and annual survey questionnaires related to quality of life and self-reported events pertinent to the CSP #465 study.

Detailed Description
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Diabetes mellitus is a major health problem in the U.S., especially in the VA population. The majority of diabetics are Type 2, and they are at risk for microvascular (e.g. eye, kidney) and macrovascular (e.g. cardiovascular) complications. It is probable that many of the macrovascular and microvascular complications potentially prevented by the 5-7 years of good Glycemic control achieved in the VADT (median follow-up 6.25 years) will occur years after completion of the VADT experimental protocol. This follow-up study will provide the opportunity to see if this holds true up to 9 years following the end of 465. The results will help the VA in evaluating most appropriate treatments and costs of such treatment. This is a longitudinal observational follow-up study of CSP #465, Glycemic Control and Complications in Diabetes Mellitus Type 2,the VA Diabetes Trial (VADT) NCT #00032487. The objectives are: 1) to determine the long term effects of intensive glycemic control in type 2 diabetes on major cardiovascular complications (primary outcome), and 2) to determine the long term effects of intensive glycemic control in type 2 diabetes on four secondary outcomes: a) cardiovascular mortality, b) major microvascular complications, c) health-related quality of life, and d) total mortality. All patients active at the end of VADT will be approached for participation in VADT-FS. The only exclusion reason will be failure to receive consent for participation. Consented VADT-FS patients will be followed until the end of the study unless they withdraw their consent. Patients will be sent a short, standardized self-administered survey annually. Information collected will include: 1) self-reported health status; 2) occurrence of study endpoints; and 3) VA or non-VA outpatient visits, hospitalizations and procedures. A variety of data sources will be searched to verify endpoints. These sources include: 1) VA and non-VA medical records; 2) data from the Centers for Medicare and Medicaid Services (CMS); and 3) VA and US death records. Patients who do not respond to 3 mailed surveys will be contacted by phone. If still unsuccessful, their designated surrogate will be contacted. Certain endpoints will be adjudicated by the same committee that was utilized by VADT. Endpoints that will be adjudicated will include: 1) cause of death; 2) reason for amputation; and 3) cardiac-related non-VA hospitalizations. Endpoints of interest in this study include: 1) mortality; 2) acute myocardial infarction requiring hospitalization; 3) stroke; 4) new onset congestive heart failure; 5) coronary revascularization; 6) amputation; 7) peripheral revascularization; 8) renal insufficiency; 9) severe visual impairment; and 10) self-reported health status (diabetes-related quality of life).

Official Title
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CSP #465FS - VA Diabetes Trial Long Term Follow-up Study

Conditions
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Diabetes, Glycemic Control

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients active at the end of VADT will be approached for participation. Exclusion Criteria: The only exclusion criterion will be failure to achieve consent for continued participation.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 465 VADT participants<br>The participants had previously participated in the VADT CSP #465 study | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Long Term Effect of Intensive Glycemic Control in Type 2 Diabetes on Major Cardiovascular Complication. | Major CV events (non-fatal MI resulting in hospitalization, non-fatal stroke, new Congestive Heart Failure (CHF), amputation for ischemic diabetic gangrene, or CV-related death). | 15 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Long Term Effects of Intensive Glycemic Control in Type 2 Diabetes on the Secondary Outcome Total Mortality. | The major secondary end-point of cardiovascular (CV) mortality will measure the cause of death (end-stage renal disease, amputation for either ischemic or non-ischemic gangrene, CV-related death, or nonfatal myocardial infarction (MI), stroke, or new congestive heart failure (CHF)) retrieved by the National Death Index (NDI). Survival analysis will analyzed by time of event to death. | 15 years | 
| The Long Term Effects of Intensive Glycemic Control in Type 2 Diabetes on the Secondary Outcome Cardiovascular Mortality. | The major secondary end-point of total mortality will measure all deaths with data retrieved from VA Information Resource Center (VIREC) Cooperate Data Warehouse (CDW) . Survival analysis will analyzed by time to death. | 15 years | 
| Number of Events on Major Microvascular or Macrovascular Outcome | End-stage renal disease, amputation for either ischemic or non-ischemic gangrene, CV-related death, or nonfatal MI, stroke, or new CHF. | 15 years | 
| Patients Reported Health Related Quality of Life | Self-reported health status using an instrument adapted for type 2 diabetes mellitus patients from the Diabetes Control and Complications Trial (DCCT) (Duckworth, 1998; Saudek 1996). This survey tool has been used since the inception of the VADT and will be continued in the annual survey. The minimum value is 0 and the maximum value is 100. The higher score is a better outcome. | 9 years |