Heterogeneity of Diabetes: Integrated Muli-Omics to Identify Physiologic Subphenotypes and Evaluate Targeted Prevention

NCT ID: NCT06682351

Last Updated: 2024-11-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-30
• Study Completion Date: 2027-12-31

Brief Summary

The study team will invite participants with prediabetes or mild diabetes (HbA1c 5.7-7.0) to join a 5-year research study that will define subphenotypes of type 2 diabetes based on underlying physiology (eg insulin resistance, beta-cell dysfunction, incretin defect, liver insulin resistance) and then test the hypothesis that response to three first-line treatments will vary according to metabolic subphenotype. Variables of interest include glucose, cardiovascular risk markers, and weight. Treatments include Mediterranean diet, metformin, and a GLP-1 agonist. Participants will go through an initial screening, followed by three treatment periods, each lasting 4 months with 3 month washout in-between treatment periods. This study will help us understand how personalized treatments can help control blood glucose, reduce cardiovascular risk, and manage weight. While there may be minor side effects-like slight discomfort from blood tests, gastrointestinal symptoms from some of the medications, and small radiation exposure from DXA body scans-the treatments offered in this study have all been well studied and are known to lower risk for diabetes and cardiovascular disease

Conditions

Prediabetes / Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Mediterranean Diet/GLP1a/Metformin

1. 16 weeks of following a Mediterranean diet: a mostly plant-based diet that includes vegetables, whole grains, whole fruits, legumes, nuts and seeds, with fish being the primary animal protein, and olive oil the primary fat.

2. 3 months washout

3. 16 weeks using GLP1 agonist: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols.

4. 3 months washout

5. 16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week.

GLP-1A

Intervention Type: DRUG

16 weeks using GLP1a: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols.

MED

Intervention Type: DIETARY_SUPPLEMENT

16 weeks of following a Mediterranean diet: a mostly plant-based diet that includes vegetables, whole grains, whole fruits, legumes, nuts and seeds, with fish being the primary animal protein, and olive oil the primary fat.

Metformin/Mediterranean Diet/GLP1a

1. 16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week.

2. 3 months washout

3. 16 weeks of following a Mediterranean diet: a mostly plant-based diet that includes vegetables, whole grains, whole fruits, legumes, nuts and seeds, with fish being the primary animal protein, and olive oil the primary fat.

4. 3 months washout

5. 16 weeks using GLP1 agonist: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week.

GLP-1A

Intervention Type: DRUG

16 weeks using GLP1a: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols.

MED

Intervention Type: DIETARY_SUPPLEMENT

16 weeks of following a Mediterranean diet: a mostly plant-based diet that includes vegetables, whole grains, whole fruits, legumes, nuts and seeds, with fish being the primary animal protein, and olive oil the primary fat.

GLP1a/Metformin/Mediterranean Diet

1. 16 weeks using GLP1 agonist: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols.

2. 3 months washout

3. 16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week.

4. 3 months washout

5. 16 weeks of following a Mediterranean diet: a mostly plant-based diet that includes vegetables, whole grains, whole fruits, legumes, nuts and seeds, with fish being the primary animal protein, and olive oil the primary fat.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week.

GLP-1A

Intervention Type: DRUG

16 weeks using GLP1a: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols.

MED

Intervention Type: DIETARY_SUPPLEMENT

16 weeks of following a Mediterranean diet: a mostly plant-based diet that includes vegetables, whole grains, whole fruits, legumes, nuts and seeds, with fish being the primary animal protein, and olive oil the primary fat.

Interventions

Metformin

16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week.

Intervention Type: DRUG

GLP-1A

16 weeks using GLP1a: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols.

Intervention Type: DRUG

MED

16 weeks of following a Mediterranean diet: a mostly plant-based diet that includes vegetables, whole grains, whole fruits, legumes, nuts and seeds, with fish being the primary animal protein, and olive oil the primary fat.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

MET; Glucagon-like peptide-1 analog; Mediterranean Diet; energy-restricted Mediterranean diet

Eligibility Criteria

Inclusion Criteria

• BMI ≥23 (≥22 in Asians) kg/m2 but < 45 kg/m2
• HbA1c 5.7-8.0% while not on antihyperglycemic medications

Exclusion Criteria

• Recent (<6mos) CVD event
• active malignancy, kidney/liver disease pregnancy/lactation, chronic inflammatory disease, eating disorder, bariatric surgery
• history of acute pancreatitis
• family or personal history of medullary thyroid cancer
• current use of antihyperglycemic, diabetogenic, or weight loss medications (washout allowed if approved by primary physician)
• heavy alcohol use
• hct <30, creatinine > 1.4, ALT> 3x ULN
• physical activity >2 hours/day
• inability to come to Stanford CTRU for metabolic testing

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Tracey McLaughlin

Professor of Medicine (Endocrinology)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tracey McLaughlin, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University

Stanford, California, United States

Countries

United States

Central Contacts

Alina Choi, BS

Role: CONTACT

linachoi@stanford.edu

7144884516

Jasmine Yang, BA

Role: CONTACT

jasminey@stanford.edu

Facility Contacts

Alina Choi, BS

Role: primary

linachoi@stanford.edu

Other Identifiers

76481

Identifier Type: -

Identifier Source: org_study_id