Effect of Saxagliptin and Dapagliflozin on Endothelial Progenitor Cell in Patients With Type 2 Diabetes Mellitus

• Status: Recruiting
• Trial end date: 2021-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The Investigator hypothesize that Dapagliflozin will improve EPC number and function AND Saxagliptin in addition to Dapagliflozin (additive effect) may improve EPC number and function even more than Dapa alone, compared to placebo.

The Investigator propose a 3-arm randomized, parallel group, longitudinal study of 16-week intervention duration. Participants will be randomized to 3 groups:

Group A: Dapa (10 mg) + Saxa Placebo, Enroll n=15, retain n=12 Group B: Dapa (10 mg) + Saxa (5 mg), Enroll n=15, retain n=12 Group C: Dapa Placebo + Saxa Placebo, Enroll n=15, retain n=12

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sabyasachi Sen
• Treatments: Dapagliflozin; Saxagliptin

Criteria

Inclusion Criteria:

1. Able to understand the study, and provide a signed & dated informed consent.

2. Diagnosis of Type 2 diabetes mellitus using criteria of the American Diabetes Association.

3. 30-70 years old.

4. HbA1C 7 to 10%, both inclusive

5. BMI of 25 - 39.9 kg/m2 both inclusive.

6. Taking a stable dose (for 12 weeks) of Metformin (any dosage) and/or Insulin (any dosage) for the treatment of T2DM

7. Patients with current Cardiovascular Disease (CVD) in tye 2 diabetes patients, defined by ≥ 1 of the following:

1. MI >2 months prior

2. Multivessel CAD

3. Angina (intermittent or chronic)

4. Single vessel CAD with positive stress test or UA hospitalization in prior year

5. UA >2 months prior and evidence of CAD

6. Stroke >2 months prior

7. Occlusive PAD

8. Proteinuria of more than 30mg/dl

Exclusion Criteria:

1. Planned CV surgery or angioplasty in 1 month

2. Prior surgery with chronic malabsorption (eg, bariatric) in prior 1 year

3. Diagnosis of Type 1 diabetes mellitus

4. History of GAD antibody positive status

5. Uncontrolled Inflammatory Disease/Inflammatory drug use. **Evaluated by PI on case-by-case basis**

6. Recent history of diabetic keto-acidosis in the past 3months, or recurrent history of diabetic ketoacidosis (≥ 3 times)

7. Active bladder cancer

8. Active wounds (e.g. Diabetic ulcers) or recent surgery within 1 month

9. Untreated hyper/hypothyroidism

10. Women of child bearing potential who are not willing to use a contraceptive method to avoid pregnancy for the 16 weeks of study duration

11. Women who are pregnant or breastfeeding

12. Implanted devices (eg. Pacemaker) that may interact with Tanita scale

13. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial Concomitant Medications

14. Taking any other oral anti-diabetic agent other than Metformin and/or Insulin for their treatment of T2DM

15. Beginning statin medications in the past 1 month or change in statin dose in the past 1 month

16. Use of consistent long-term steroid medication (oral, inhaled, injected) within the last 1 month

17. Treatment with a strong cytochrome P450 3A4 (CYP34A) or P-gp inducer (ie. Rifampin)

18. Subjects with a history of any serious hypersensitivity reaction to Dapagliflozin / Saxagliptin or another SGLT-2 inhibitor/ DPP4 inhibitor Laboratory Findings

19. Uncontrolled hyperglycemia, defined as a fasting glucose >240 mg/dL (>13.3 mmol/L) at screening.

20. Liver disease with ALT, AST or ALP x3 ULN

21. eGFR < 60 mL/min/1.73 m2 by MDRD equation in the past 3 months

22. Clinically significant RBC disorders such as hemoglobinopathies

23. Serum creatinine levels ≥1.8 mg/dL with estimated eGFP < 60 mL/min

24. Triglycerides > 450 mg/dL

25. Baseline Hematuria (judged by a urinalysis dipstick at screening) Social History

26. Active smokers

27. Chronic or persistent alcohol or drug abuse

28. Prisoners or subjects who are involuntarily incarcerated

29. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg. infectious disease) illness

30. Participation in another trial with an investigational drug within 30 days prior to informed consent