Prevention of Progression of Prediabetes, Obesity and CV Risk

Phase 1

Recruiting

• Conditions: Pre-Diabetes; Cardiovascular Diseases; Weight, Body
• Interventions: Drug: Placebo; Drug: Jardiance 25Mg Tablet; Drug: Rybelsus Tablet; Drug: Metformin; Drug: Actos

• Registration Number: NCT06446531
• Lead Sponsor: The University of Texas Health Science Center at San Antonio

Brief Summary

The investigators are studying how to help people with prediabetes (Pre-DM) and obesity. The goal is to use new and affordable treatments to bring blood sugar levels back to normal and help participants to lose weight. The investigators also want to reduce participants risk of heart problems. The study team will look at how these treatments affect metabolism and other body functions to help find new ways to treat diabetes and obesity in the future.

Detailed Description

While taking part in this study, participants will be asked to attend approximately 16 visits with the researchers or study staff.

Study participants are assigned (single-blinded, only the study team will know the assigned group) to one of 4 study groups, receiving a 6-month treatment with Nutritional Consultation + either SGLT2 Inhibitor (Empagliflozin), Rybelsus (GLP1 Receptor Agonist), Metformin + Pioglitazone, or placebo. A placebo is an inactive, harmless substance that looks like the other study drugs. This study does not require overnight stays at the hospital in any of the study groups.

Duration of the Study will be about 6-7 months.

Study Timeline

• Study First Submitted: 2024-05-31
• Study First Submitted QC: 2024-05-31
• Study First Posted: 2024-06-06
• Study Start: 2024-09-11
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-15
• Last Update Posted: 2024-10-17
• Primary Completion: 2027-07
• Study Completion: 2027-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

1. Patients will have an established diagnosis of pre-Diabetes Mellitus (DM) before the screening visit, documented by an acceptable modality in the last 6 months.

2. Age ≥ 18 years old

3. Body Mass Index (BMI)=25-40 kg/m2

4. Glycated Hemoglobin (HbA1c) = 5.7-6.4%

5. Blood Pressure (BP) <160/100

6. Estimated Glomerular Filtration Rate (eGFR) ≥30 ml/min•1.73m2

7. Body weight must be stable (±5 pounds) over the last 3 months.

8. Oral diuretics, if prescribed to the patient according to local guidelines and discretion of the investigator, should be stable for at least 1 week prior to randomization.

9. Hispanic ethic group

10. Willing to adhere to medication regimen for up to 6 months.

11. Male or female, if female, met these criteria:

    1. Not pregnant or breast-feeding
    2. Negative pregnancy test result at visit 1 (screening)
    3. During the entire study, women of childbearing potential (WOCBP) including peri-menopausal women who have a menstrual period within 1 year must practice appropriate, and effective birth control, either implants or pills, or a vasectomized partner prior to receiving the first dose of study medication

12. Does not suffer from severe claustrophobia

13. No contraindication for Magnetic Resonance Imaging (MRI) (metal plates, screws, shrapnel, pins, or cardiac pacemaker)

Exclusion Criteria

1. Patients currently on one of the selected therapies
2. Extended diagnoses with Type 2 Diabetes
3. Pregnancy, lactation, women of childbearing age (WOCBA) unwilling to use contraception
4. Known allergy/sensitivity to study drugs or their ingredients
5. Major oncologic diagnosis in the last 5 years
6. Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
7. Inability or unwillingness of individual or legal guardian/representative to give written informed consent
8. Major organ or metabolic diseases, or physical limitations that will not allow the subject to complete the study
9. Myocardial infraction, coronary artery bypass graft surgery, or other major cardiovascular event in the past 60 days
10. Heart transplant recipient or listed for a heart transplant
11. Currently implanted left ventricular assist device
12. Cardiomyopathy based on infiltrative or cumulative hypertrophic obstructive cardiomyopathy or known pericardial constriction
13. Any severe (obstructive or regurgitant) valvular heart disease, expected to lead to surgery during the trial period
14. Acute decompensated heart failure requiring intravenous diuretics, vasodilators, inotropic agents, or mechanical support within 1 week of screening and during the screening period prior to randomization
15. Implanted cardioverter defibrillator within 3 months prior to screening
16. Cardiac resynchronization therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Randomization will occur 1:1:1:1 to this placebo group
SGLT2 inhibitor Group	Jardiance 25Mg Tablet	Randomization will occur 1:1:1:1 to this SGLT2 inhibitor group
Metformin with SGLT2 Inhibitor Group	Actos	Randomization will occur 1:1:1:1 to this metformin plus SGLT2 inhibitor group
GLP-1 Receptor Agonist Group	Rybelsus Tablet	Randomization will occur 1:1:1:1 to this GLP-1 receptor agonist group
Metformin with SGLT2 Inhibitor Group	Metformin	Randomization will occur 1:1:1:1 to this metformin plus SGLT2 inhibitor group

Primary Outcome Measures

Name	Time	Method
Hemoglobin A1c Level (HBA1c)	Baseline and 6 months	Percentage of glycated hemoglobin level in blood

Secondary Outcome Measures

Name	Time	Method
Body Mass Index (BMI)	Baseline and 6 months	Measure of body fat based on height and weight that applies to adult men and women
Percentage of Body Fat Composition	Baseline and 6 months	Measurement of body fat using a DEXA scan
Left Ventricular Function	Baseline and 6 months	Cardiac function is measured by left-ventricular function measured using cardiac MRI and expressed as a percentage
Measure of phosphocreatine k-value	Baseline and 6 months	A skeletal muscle bioenergetic measurement using skeletal muscle MRI/MRS
Measure of oxidative capacity	Baseline and 6 months	A skeletal muscle bioenergetic measurement using skeletal muscle MRI/MRS
Patient Reported Outcomes (PROMIS)	Baseline and 6 months	A survey used to assess physical function. Subjects will rank 20 questions from a scale of 1 - 5, with 5 being the highest physical function and 1 being the lowest. The score will be added up, and the Raw score will be converted to T-Score using the PROMIS Adult v2.0 Physical Function 20a Short Form Conversion Table. The range of T-scores is 12.1-62.5. A higher score indicates higher physical function.
Measure of intramyocellular lipids (IMCL)	Baseline and 6 months	A skeletal muscle bioenergetic measurement using skeletal muscle MRI/MRS
Measure of extramyocellular lipids (EMCL)	Baseline and 6 months	A skeletal muscle bioenergetic measurement using skeletal muscle MRI/MRS

Trial Locations

Locations (1)

University of Texas Health Science Center at San Antonio; 🇺🇸 San Antonio, Texas, United States