Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Changing the Natural History of Type 2 Diabetes ("CHANGE" Study) (CHANGE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05040087
Recruitment Status : Recruiting
First Posted : September 10, 2021
Last Update Posted : September 10, 2021
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Emory University
Abbott Diabetes Care
Information provided by (Responsible Party):
Mary Rhee, MD, Atlanta VA Medical Center

Brief Summary:
Diabetes is a disorder of high blood glucose, that tends to get worse; over time, patients need more and more drugs. This pattern is caused by overwork of the body's insulin-producing β-cells, because patients' glucose levels are typically above normal; if the investigators kept glucose levels normal - reducing β-cell work - the investigators might be able to keep the disease from getting worse. This trial is aimed to show that adjusting the drugs to keep glucose levels normal, can help to preserve β-cell function compared to usual diabetes care, possibly reduce the tendency to develop the eye and kidney complications of diabetes, and might also be more cost-effective than usual care.

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

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: While the study is unblinded, investigators will be blinded to the randomization plan.
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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)
  1. Guidance by SMBG:
  2. Glucose goals: We will aim for <100 mg/dl premeal (2), <130 postmeal.
  3. Monitoring will include pre-breakfast 2x/wk, and a 5-point profile 1x/wk (before and 1.5-2.5 hr after breakfast, before lunch, before supper, and bedtime).
  4. Added Rx will be used if SMBG is >goal ≥3x in 2 consecutive weeks after ≥4 weeks of MOVE! and/or the previous Rx [e.g., any 3 of the 7 goals (<100 mg/dl premeal, <130 post)]. Metformin ER will be given first (if not already on it), and increased to 2000 mg/day if there are no side effects. (If metformin is not tolerated, it will be stopped and the second Rx will become the "first Rx" and given instead. If other Rx are not tolerated, the next Rx will be used. The second Rx will be the TZD pioglitazone, followed by the GLP-1 RA semaglutide, then the SGLT-2 inhibitor empagliflozin. If still above goal, glargine insulin will be added, titrated to keep fasting glucose <100 mg/dl.
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.




Primary Outcome Measures :
  1. EFFECT SIZE [ Time Frame: 2.75 years (includes 3 month washout) ]
    HbA1c DIFFERENCEs, INTENSIVE Rx vs. CONTROLS - PRIMARY OUTCOME #1

  2. 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.

  3. 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.

  4. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • diagnosis of diabetes by OGTT
  • age 40-74 years
  • HbA1c 6.0-7.4%
  • 1 hr OGTT glucose >155 mg/dl in each group

Exclusion Criteria:

  • CVD event during the previous year
  • systemic glucocorticoids
  • bariatric surgery
  • stage III-IV congestive heart failure
  • severe angina
  • life expectancy <5 years
  • BMI >40 kg/m2
  • pregnancy
  • pancreatitis
  • family or personal history of multiple endocrine neoplasia 2a
  • an estimated glomerular filtration rate [eGFR] of ≤50 ml/min
  • an alanine aminotransferase (ALT) level >3x the upper limit of the normal range
  • dementia

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Mary K Rhee, MD, MSCR 404-321-6111 ext 202080 mrhee@emory.edu
Contact: Lawrence S Phillips, MD 404-728-7608 medlsp@emory.edu

Locations
Layout table for location information
United States, Georgia
Atlanta VA Medical Center Recruiting
Decatur, Georgia, United States, 30033
Contact: Stephanie T Raines, MA    404-321-6111 ext 206932    tasha.raines@va.gov   
Contact: Radhika Mungara, MS    404-321-6111    radhika.mungara@va.gov   
Principal Investigator: Mary K Rhee, MD, MSCR         
Sub-Investigator: Lawrence S Phillips, MD         
Sponsors and Collaborators
Foundation for Atlanta Veterans Education and Research, Inc.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Emory University
Abbott Diabetes Care
Investigators
Layout table for investigator information
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
  Study Documents (Full-Text)

Documents provided by Mary Rhee, MD, Atlanta VA Medical Center:
Informed Consent Form  [PDF] July 23, 2021

Publications of Results:
Layout table for additonal information
Responsible Party: Mary Rhee, MD, Associate Professor of Medicine, Emory University School of Medicine, Atlanta VA Medical Center
ClinicalTrials.gov Identifier: NCT05040087    
Other Study ID Numbers: 2107
1R01DK127083-01A1 ( U.S. NIH Grant/Contract )
First Posted: September 10, 2021    Key Record Dates
Last Update Posted: September 10, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Final data sets underlying all publications resulting from the proposed research will be shared outside VA. A de-identified, anonymized dataset will be created and shared. Data will be shared upon request in a format available per VA mechanisms. After the data has been published, all requests will be reviewed, and data sets deemed appropriate for release will be provided to the requestor in electronic format. Data will be stored and maintained in an approved location as described in the VA Research Data Inventory Form kept on file in the research office.
Supporting Materials: Study Protocol
Time Frame: Final data sets underlying all publications resulting from the proposed research will be shared outside VA. A de-identified, anonymized dataset will be created and shared. Data will be shared upon request in a format available per VA mechanisms. After the data has been published, all requests will be reviewed, and data sets deemed appropriate for release will be provided to the requestor in electronic format. Data will be stored and maintained in an approved location as described in the VA Research Data Inventory Form kept on file in the research office.
Access Criteria: Final data sets underlying all publications resulting from the proposed research will be shared outside VA. A de-identified, anonymized dataset will be created and shared. Data will be shared upon request in a format available per VA mechanisms. After the data has been published, all requests will be reviewed, and data sets deemed appropriate for release will be provided to the requestor in electronic format. Data will be stored and maintained in an approved location as described in the VA Research Data Inventory Form kept on file in the research office.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases