Impact of Semaglutide on CD34+ EPC and Fat Derived MSC

• Status: Recruiting
• Trial end date: 2021-11-30
• Target enrollment: 0
• Participant gender: All

Summary

The Investigator is trying to ascertain whether an FDA approved medication of T2DM, Semaglutide, can improve the number, function and gene expression of subjects CD34+ endothelial progenitor cells. EPCs are the source of cells protecting the inner lining of blood vessels and improving their survivability will improve cardiovascular outcome as high glucose environment of diabetes are toxic to these EPC Cells.

Improve mitochondrial metabolism of Mesenchymal Stem Cell from subcutaneous fatty tissue, leading to weight loss. Improve overall vascular health by reducing inflammation.

The investigator will enroll 40 subjects with T2DM who are only on metformin. The study consists of 4 visits to the GW MFA, including screening visit. Subjects will be recruited from across the DMV area, and prescreened over the phone or in clinic, and then invited for an in-person screening visit at the GW MFA to determine eligibility. If eligible, subject will be enrolled into one of two study Arms, active semaglutide 1 mg or Placebo. This study will include an up titration of study drug. From week 0-4 subject will be on 0.25 mg/week, from week 5-8 subject will take 0.5mg/week, and week 9 to 24 subject will take 1 mg/week of Semaglutide or Placebo.

During the regular 3 visits subject will have their vital measured, body composition assessed using Tanita scale, arterial stiffness measured and blood drawn for EPC cells analysis and standard of care labs. At visit 1 and visit 3, fat biopsy will be done on the belly area to acquire 2-3 grams of fat tissue. Screening will take place at week -2, Visit1 at week 0, Visit 2 at week 8, Visit 3 at week 24. Subject will receive follow-up phone calls on week 4, week16 and week 28.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sabyasachi Sen

Criteria

Inclusion Criteria:

1. Age 30-70

2. Diagnosed with Type 2 diabetes mellitus

3. Body Mass Index (BMI) between 25.0-45.0 (both inclusive)

4. eGFR ≥ 30 mL/min/1.73 m2 by MDRD

5. HbA1C 7.0 - 10.0 %

6. Subjects on a stable dose of Metformin (1-2 grams), only, for 3 months prior to screening.

7. Ability to provide informed consent (and document informed consent by signature) before any trial-related activities are conducted.

8. Additional CVD risk factor such microalbuminuria or proteinuria (as defined by ADA, UACR > 30 mg/g), hypertension (labile and uncontrolled hypertension) and left ventricular hypertrophy, left ventricular systolic or diastolic dysfunction, or an ankle- brachial index [the ratio of the systolic blood pressure at the ankle to the systolic blood pressure in the arm] of less than 0.9, low HDL with hypertriglyceridemia (as defined by NCEP ATP III) , strong family history of CHD (as defined by NCEP ATP III and ATP IV).

9. Retinal examination within last 18 months of enrollment, showing no proliferative retinopathy

Exclusion Criteria:

1. Uncontrolled hyperglycemia with fasting glucose >240 mg/dL (>13.3 mmol/L)

2. Liver disease with ALT, AST or ALP ≥ x3 ULN

3. Planned CV surgery or angioplasty in the past 1 month

4. History of established CVD

5. Known personal history of cerebral stroke or heart attack ( myocardial infarction)

6. All other diabetes medications other than metformin

7. Personal or family history of medullary thyroid cancer (MTC)

8. Personal or family history of Multiple Endocrine Neoplasia Syndrome Type 2 (MEN 2)

9. GFR <30 mL/min/1.73 m2 by MDRD

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

11. Clinically significant RBC disorders such as hemoglobinopathies

12. Diagnosis of Type 1 diabetes mellitus or history of GAD antibody positive status

13. Chronic use of anti-inflammatory drugs for the last 3 months

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

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

16. History of pancreatitis

17. Known or suspected allergy to GLP-1 agonists, excipients, or related products.

18. Active smokers

19. Active wounds (i.e. diabetic ulcers) or recent surgery within 1 month

20. Untreated hyper/hypothyroidism

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

22. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial

23. Women of child bearing potential who are not willing to use a contraceptive method to avoid pregnancy for the 16 weeks of study duration plus 2 months post treatment (for semaglutide washout).

24. Women who are pregnant or breastfeeding

25. Chronic or persistent alcohol or drug abuse

26. Prisoners or subjects who are involuntarily incarcerated

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

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

29. Untreated or active hemorrhagic proliferative diabetic retinopathy Exclusionary Laboratory Findings

30. Chronic Kidney Disease (CKD) stages 4 and 5 (estimated CrCl less than 30 mL/min)

31. Serum creatinine levels ≥1.8 with estimated CrCl < 60 mL/min

32. Triglycerides > 500 mg/dL

33. Low hematocrit (<28 Units)