Impact of Semaglutide on CD34+ EPC and Fat Derived MSC

NCT04126603 | Completed Phase 4 Results FDA Drug

• 1 other identifier: NCR191206
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (4)

• CD34+ Endothelial Progenitor Cell Number (EPC) Per Mononuclear Cells (MNC) Ratio

  Number of CD34+ EPCs per total MNC ratio. Please note CD34+ cells is a progenitor cell marker derived from mononuclear cells (MNCs).

  First Visit at Baseline and Last Visit at 24 weeks

• CD34+ Endothelial Progenitor Cell Migration (EPC) Against Serum SDF1a Gradient

  The distance the CD34+ EPC migrates in response to SDF1 alpha 10ng. This assess the mobility of stem cells such as CD34+ EPC and the distance it traveled would lead us to understand how medication therapy changes stem cell behavior and its functionality.

  First Visit at Baseline and Last Visit at 24 weeks

• Gene Expression of CD34+ Endothelial Progenitor Cell Number

  we will evaluate mRNA gene expression of endothelial Progenitor cell with catalase, KDR, NOS3,SOD2, TNF-alpha which is normalized to 18s. Fold change of particular genes in hematopoietic stem cells between baseline and terminal visit at week 24 were analyzed.

  First Visit at Baseline and Last Visit at 24 weeks

• CD34+ Endothelial Cell Colony Formation Unit (CFU)

  CFU count of CD34+ EPCs

  First Visit at Baseline and Last Visit at 24 weeks

Secondary Outcomes (9)

• Gene Expression of Subcutaneous Adipose Cell

  First Visit at Baseline and Last Visit at 24 weeks

• Arterial Stiffness: Pulse Wave Analysis Augmentation Index

  First Visit at Baseline and Last Visit at 24 weeks

• Arterial Stiffness: Pulse Wave Analysis Augmentation Pressure

  First Visit at Baseline and Last Visit at 24 weeks

• Arterial Stiffness: Pulse Wave Analysis Augmentation Index 75

  First Visit at Baseline and Last Visit at 24 weeks

• Body Composition: BMI

  First Visit at Baseline and Last Visit at 24 weeks

Study Arms (2)

Group A Placebo

PLACEBO COMPARATOR

Placebo.

Drug: Placebos

Group B Active

ACTIVE COMPARATOR

Semaglutide

Drug: Semaglutide

Interventions

Semaglutide DRUG

0.25mg/week for week 0 - 4 , then increasing to 0.5mg/week for weeks 5 - 8, then 1 mg/week for week 9 - 24 weeks

Group B Active

Placebos DRUG

Placebo injection

Group A Placebo

Eligibility Criteria

• Age: 20 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 20-90
• Diagnosed with Type 2 diabetes mellitus
• Body Mass Index (BMI) between 25.0-45.0 (both inclusive)
• eGFR ≥ 30 mL/min/1.73 m2 by MDRD
• HbA1C 6.5 - 12.0 %
• Subjects on lifestyle modification alone, or Metformin (0.5-2 grams), insulin, or in combination, in any doses of either Metformin or Insulin for at least 3 months prior to screening. 2 week washout of any other anti-hyperglycemic.
• Ability to provide informed consent (and document informed consent by signature) before any trial-related activities are conducted.
• Additional CVD risk factor such microalbuminuria or proteinuria (as defined by ADA, UACR \> 30 mg/g), hypertension (labile, uncontrolled hypertension or controlled on anti-hypertensives) 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).
• Retinal examination within last 2 years of enrollment, showing no proliferative retinopathy

You may not qualify if:

• Uncontrolled hyperglycemia with fasting glucose \>300 mg/dL (\>16.6 mmol/L)
• Liver disease with ALT, AST or ALP ≥ x3 ULN
• Known (recent) personal history of cerebral stroke or heart attack (myocardial infarction) within last 6 months
• Personal or family history of medullary thyroid cancer (MTC)
• Personal or family history of Multiple Endocrine Neoplasia Syndrome Type 2 (MEN 2)
• GFR \<30 mL/min/1.73 m2 by MDRD
• Prior surgery with chronic malabsorption (eg, bariatric) within last 1 year
• Clinically significant RBC disorders such as hemoglobinopathies
• Diagnosis of Type 1 diabetes mellitus or history of GAD antibody positive status
• Chronic use of high dose anti-inflammatory drugs for the last 3 months
• Beginning statin medications or change in statin dose within the past 1 month
• Starting use of high-dose steroid medication (100mg hydrocortisone or 40mg prednisone equivalent) within the last 1 month
• History of acute pancreatitis within the past 2 years
• Known or suspected allergy to GLP-1 agonists, excipients, or related products.
• Active smokers, \>5 per day (at present)

Sponsors & Collaborators

• Sabyasachi Sen: lead

Study Sites (2)

The GW Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

Location

Washington VA Medical Center

Washington D.C., District of Columbia, 20422, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

semaglutide

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Sabyasachi Sen
• Organization: George Washington University

ssen1@gwu.edu

202-994-8560

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 7, 2019
• First Posted: October 15, 2019
• Study Start: August 1, 2019
• Primary Completion: October 25, 2023
• Study Completion: May 14, 2025
• Last Updated: September 9, 2025
• Results First Posted: September 9, 2025

Record last verified: 2025-08

Locations

US (2)