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

NCT05040087 | Active Not Recruiting

• 2 other identifiers: 21071R01DK127083-01A1
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (4)

• EFFECT SIZE

  HbA1c DIFFERENCEs, INTENSIVE Rx vs. CONTROLS - PRIMARY OUTCOME #1

  2.75 years (includes 3 month washout)

• β-CELL FUNCTION - PRIMARY OUTCOME #2a

  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.

  2.75 years (includes 3 month washout)

• β-CELL FUNCTION - PRIMARY OUTCOME #2b

  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.

  2.75 years (includes 3 month washout)

• β-CELL FUNCTION - PRIMARY OUTCOME #2c.

  β-cell function as the 1 hour OGTT plasma glucose (1hrOGTT).

  2.75 years (includes 3 month washout)

Secondary Outcomes (5)

• RETINOPATHY determined by fundus photographs

  2.5 years

• NEPHROPATHY by eGFR

  2.5 years

• NEPHROPATHY by urine microalbumin/creatinine ratio

  2.5 years

• Point of care glucose by continuous glucose monitoring (CGM)

  2.5 years

• COST EFFECTIVENESS - to be explored only if additional (ancillary) funding can be obtained

  2.5 years

Study Arms (2)

USE OF DIABETES Rx GUIDED LARGELY BY HbA1c LEVELS

ACTIVE COMPARATOR

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 GUIDED BY SELF-MONITORED BLOOD GLUCOSE (SMBG)

EXPERIMENTAL

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

Interventions

Intensification of diabetes medication based largely on HbA1c levels OTHER

Use of diabetes Rx in controls will be guided largely by HbA1c levels.

USE OF DIABETES Rx GUIDED LARGELY BY HbA1c LEVELS

Intensification of diabetes medication based on glucose levels OTHER

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.

USE OF DIABETES Rx GUIDED BY SELF-MONITORED BLOOD GLUCOSE (SMBG)

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• diagnosis of diabetes by OGTT
• age 40-75 years
• HbA1c 6.0-7.4%
• hr OGTT glucose \>155 mg/dl in each group

You may not qualify if:

• 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

Sponsors & Collaborators

• Foundation for Atlanta Veterans Education and Research, Inc.: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Emory University: collaborator
• Abbott Diabetes Care: collaborator

Study Sites (1)

Atlanta VA Medical Center

Decatur, Georgia, 30033, United States

Location

Related Publications (1)

• Phillips LS, Ratner RE, Buse JB, Kahn SE. We can change the natural history of type 2 diabetes. Diabetes Care. 2014 Oct;37(10):2668-76. doi: 10.2337/dc14-0817.

  PMID: 25249668 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Mary K Rhee, MD, MSCR

  Emory University School of Medicine, Atlanta VA Medical Center

  PRINCIPAL INVESTIGATOR

• Lawrence S Phillips, MD

  Emory University School of Medicine, Atlanta VA Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: While the study is unblinded, investigators will be blinded to the randomization plan.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Emory University School of Medicine

Study Record Dates

• First Submitted: August 27, 2021
• First Posted: September 10, 2021
• Study Start: September 1, 2021
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: May 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: 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.

Locations

US (1)