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

Diabetes Clinical Trial

— VADT-F  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00756613
• Other study ID #: 465FS
• Status: Completed
• Start date: February 1, 2008
• Est. completion date: December 31, 2017

Study information

• Verified date: June 2019
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1044
• Est. completion date: December 31, 2017
• Est. primary completion date: December 31, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Glycemic Control

Locations

Country	Name	City	State
United States	Hines VAMC, Hines IL	Hines	Illinois
United States	Phoenix VA Health Care System, Phoenix, AZ	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

References & Publications (17)

Agrawal L, Azad N, Bahn GD, Ge L, Reaven PD, Hayward RA, Reda DJ, Emanuele NV; VADT Study Group. Long-term follow-up of intensive glycaemic control on renal outcomes in the Veterans Affairs Diabetes Trial (VADT). Diabetologia. 2018 Feb;61(2):295-299. doi: — View Citation

Anderson RJ, Bahn GD, Emanuele NV, Marks JB, Duckworth WC; VADT Study Group. Blood pressure and pulse pressure effects on renal outcomes in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care. 2014 Oct;37(10):2782-8. doi: 10.2337/dc14-0284. Epub 201 — View Citation

Azad N, Agrawal L, Emanuele NV, Klein R, Bahn GD, McCarren M, Reaven P, Hayward R, Duckworth W; VADT Study Group. Association of PAI-1 and fibrinogen with diabetic retinopathy in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care. 2014 Feb;37(2):50 — View Citation

Azad N, Agrawal L, Emanuele NV, Klein R, Bahn GD, Reaven P; VADT Study Group. Association of blood glucose control and pancreatic reserve with diabetic retinopathy in the Veterans Affairs Diabetes Trial (VADT). Diabetologia. 2014 Jun;57(6):1124-31. doi: 1 — View Citation

Azad N, Bahn GD, Emanuele NV, Agrawal L, Ge L, Reda D, Klein R, Reaven PD, Hayward R; VADT Study Group. Association of Blood Glucose Control and Lipids With Diabetic Retinopathy in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care. 2016 May;39(5): — View Citation

Davis SN, Duckworth W, Emanuele N, Hayward RA, Wiitala WL, Thottapurathu L, Reda DJ, Reaven PD; Investigators of the Veterans Affairs Diabetes Trial. Effects of Severe Hypoglycemia on Cardiovascular Outcomes and Death in the Veterans Affairs Diabetes Tria — View Citation

Follow-Up of Glycemic Control and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2015 Jul 9;373(2):198. doi: 10.1056/NEJMx150025. — View Citation

Hayward RA, Reaven PD, Emanuele NV; VADT Investigators. Follow-up of Glycemic Control and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2015 Sep 3;373(10):978. doi: 10.1056/NEJMc1508386. — View Citation

Hayward RA, Reaven PD, Wiitala WL, Bahn GD, Reda DJ, Ge L, McCarren M, Duckworth WC, Emanuele NV; VADT Investigators. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015 Jun 4;372(23):2197-206. doi: 10.1056/NEJ — View Citation

Herrington WG, Preiss D. Tightening our understanding of intensive glycaemic control. Lancet Diabetes Endocrinol. 2017 Jun;5(6):405-407. doi: 10.1016/S2213-8587(17)30095-5. Epub 2017 Mar 30. — View Citation

Reaven PD, Emanuele NV, Wiitala WL, Bahn GD, Reda DJ, McCarren M, Duckworth WC, Hayward RA; VADT Investigators. Intensive Glucose Control in Patients with Type 2 Diabetes - 15-Year Follow-up. N Engl J Med. 2019 Jun 6;380(23):2215-2224. doi: 10.1056/NEJMoa — View Citation

Saremi A, Howell S, Schwenke DC, Bahn G, Beisswenger PJ, Reaven PD; VADT Investigators. Advanced Glycation End Products, Oxidation Products, and the Extent of Atherosclerosis During the VA Diabetes Trial and Follow-up Study. Diabetes Care. 2017 Apr;40(4): — View Citation

Saremi A, Schwenke DC, Bahn G, Ge L, Emanuele N, Reaven PD; VADT Investigators. The effect of intensive glucose lowering therapy among major racial/ethnic groups in the Veterans Affairs Diabetes Trial. Metabolism. 2015 Feb;64(2):218-25. doi: 10.1016/j.met — View Citation

Zhou JJ, Koska J, Bahn G, Reaven P. Glycaemic variation is a predictor of all-cause mortality in the Veteran Affairs Diabetes Trial. Diab Vasc Dis Res. 2019 Mar;16(2):178-185. doi: 10.1177/1479164119827598. — View Citation

Zhou JJ, Schwenke DC, Bahn G, Reaven P; VADT Investigators. Glycemic Variation and Cardiovascular Risk in the Veterans Affairs Diabetes Trial. Diabetes Care. 2018 Oct;41(10):2187-2194. doi: 10.2337/dc18-0548. Epub 2018 Aug 6. — View Citation

Zimering MB, Knight J, Ge L, Bahn G; VADT Investigators. Predictors of Cognitive Decline in Older Adult Type 2 Diabetes from the Veterans Affairs Diabetes Trial. Front Endocrinol (Lausanne). 2016 Sep 8;7:123. doi: 10.3389/fendo.2016.00123. eCollection 201 — View Citation

Zoungas S, Arima H, Gerstein HC, Holman RR, Woodward M, Reaven P, Hayward RA, Craven T, Coleman RL, Chalmers J; Collaborators on Trials of Lowering Glucose (CONTROL) group. Effects of intensive glucose control on microvascular outcomes in patients with ty — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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