Changing the Natural History of Type 2 Diabetes ("CHANGE" Study) (CHANGE)
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|ClinicalTrials.gov Identifier: NCT05040087|
Recruitment Status : Recruiting
First Posted : September 10, 2021
Last Update Posted : September 10, 2021
|Condition or disease||Intervention/treatment||Phase|
|Type 2 Diabetes||Other: Intensification of diabetes medication based largely on HbA1c levels Other: Intensification of diabetes medication based on glucose levels||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||126 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Masking Description:||While the study is unblinded, investigators will be blinded to the randomization plan.|
|Official Title:||Changing the Natural History of Type 2 Diabetes ("CHANGE" Study)|
|Estimated Study Start Date :||September 2021|
|Estimated Primary Completion Date :||December 2025|
|Estimated Study Completion Date :||June 2026|
Active Comparator: USE OF DIABETES Rx GUIDED LARGELY BY HbA1c LEVELS
Extended-release [ER] metformin will be added if HbA1c is ≥7.0% after 3 months; if already used and maximized, pioglitazone will be begun. Other Rx will be added each time HbA1c reaches ≥7.5%. The sequence of Rx will be the same as in intensive Rx subjects; those using insulin will also do prebreakfast SMBG, aiming for glucose <100 mg/dl.
Other: Intensification of diabetes medication based largely on HbA1c levels
Use of diabetes Rx in controls will be guided largely by HbA1c levels.
Experimental: USE OF DIABETES Rx GUIDED BY SELF-MONITORED BLOOD GLUCOSE (SMBG)
Other: Intensification of diabetes medication based on glucose levels
Use of diabetes Rx in the intensive Rx groups will be guided by participants' self-monitored blood glucose levels (SMBG), with management aimed to keep glucose levels within the normal range.
- EFFECT SIZE [ Time Frame: 2.75 years (includes 3 month washout) ]HbA1c DIFFERENCEs, INTENSIVE Rx vs. CONTROLS - PRIMARY OUTCOME #1
- β-CELL FUNCTION - PRIMARY OUTCOME #2a [ Time Frame: 2.75 years (includes 3 month washout) ]β-cell function from modeling using a 3-hour OGTT with samples for glucose, insulin and C-peptide at 10, -5, 10, 20, 30, 60, 90, 120, 150 and 180 minutes.
- β-CELL FUNCTION - PRIMARY OUTCOME #2b [ Time Frame: 2.75 years (includes 3 month washout) ]β-cell function and insulin sensitivity as the oral "OGTT ISI disposition index" (DI), using the "insulinogenic index" [(Δ insulin/Δ glucose) with 0- and 30-minute insulin (and C-peptide) and glucose levels in the OGTT] for insulin secretion and [1/(fasting insulin concentration)] for insulin action.
- β-CELL FUNCTION - PRIMARY OUTCOME #2c. [ Time Frame: 2.75 years (includes 3 month washout) ]β-cell function as the 1 hour OGTT plasma glucose (1hrOGTT).
- RETINOPATHY determined by fundus photographs [ Time Frame: 2.5 years ]Assessed with fundus photos graded by readers masked to study groups. The University of Wisconsin Fundus Photograph Reading Center (FPRC) is grading photos for the DPPOS. Under Co-I Dr. Maa's direction, and with dilation, 4 sets of stereo ETDRS-level photos with 45° fields will be taken with a Zeiss Cirrus 600 camera by FPRC-certified VA technologists. Deidentified images will be uploaded via secure OneDrive, and accessed by the FPRC.
- NEPHROPATHY by eGFR [ Time Frame: 2.5 years ]The development of nephropathy will be assessed with the eGFR according to the CKD-EPI equation, measured in the Atlanta VA Clinical Laboratory, in samples obtained at baseline, and every 6 months through 2.5 years.
- NEPHROPATHY by urine microalbumin/creatinine ratio [ Time Frame: 2.5 years ]The development of nephropathy will be assessed with the urine microalbumin/creatinine ratio, measured in the Atlanta VA Clinical Laboratory, in samples obtained at baseline, and every 6 months through 2.5 years.
- Point of care glucose by continuous glucose monitoring (CGM) [ Time Frame: 2.5 years ]After 3 weeks of MOVE! and maximum tolerated dosage of each Rx in intensive Rx subjects, 14 days of CGM will permit ROC analysis to compare AG vs. SMBG in predicting need for more Rx, and use of the Youden index to define an optimal glucose cutoff. We will also assess prediction of needing the first vs. later Rx; ROC areas should be independent of disease prevalence.
- COST EFFECTIVENESS - to be explored only if additional (ancillary) funding can be obtained [ Time Frame: 2.5 years ]We will use a microsimulation model to extrapolate the glycemic reduction with intensive Rx observed in the trial to the potential reduction in DM complications and related costs in a lifetime window.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05040087
|Contact: Mary K Rhee, MD, MSCR||404-321-6111 ext firstname.lastname@example.org|
|Contact: Lawrence S Phillips, MDemail@example.com|
|United States, Georgia|
|Atlanta VA Medical Center||Recruiting|
|Decatur, Georgia, United States, 30033|
|Contact: Stephanie T Raines, MA 404-321-6111 ext 206932 firstname.lastname@example.org|
|Contact: Radhika Mungara, MS 404-321-6111 email@example.com|
|Principal Investigator: Mary K Rhee, MD, MSCR|
|Sub-Investigator: Lawrence S Phillips, MD|
|Principal Investigator:||Mary K Rhee, MD, MSCR||Emory University School of Medicine, Atlanta VA Medical Center|
|Study Director:||Lawrence S Phillips, MD||Emory University School of Medicine, Atlanta VA Medical Center|