A Double-Blind, Randomized, Placebo-Controlled Phase IIa Clinical Trial to Evaluate the Safety and Efficacy of DT2-SCT in Subjects With Type 2 Diabetes Mellitus

This clinical trial is a double-blind, randomized, placebo-controlled Phase IIa study to evaluate the safety and efficacy of DT2-SCT, an autologous adipose-derived mesenchymal stem cell (MSC) therapy, in adults with Type 2 Diabetes Mellitus (T2DM). The study will explore the potential of DT2-SCT to improve glycemic control, reduce insulin resistance, and decrease dependency on insulin and oral glucose-lowering drugs.

Study Design:

The trial involves 120 participants, randomized in a 1:1 ratio to receive either DT2-SCT or a placebo. The investigational product, DT2-SCT, consists of MSCs isolated from each participant's adipose tissue obtained via a tumescent liposuction procedure. The cells are processed, expanded, and prepared in a sterile, cryopreservation-free medium for a single intravenous infusion. The placebo consists of Plasma-Lyte A without MSCs.

Intervention and Monitoring:

Participants will undergo:

Screening and Enrollment: Eligibility will be determined based on inclusion and exclusion criteria, including a comprehensive review of medical history, laboratory tests, and diabetes status.

Liposuction Procedure: Approximately 50 mL of adipose tissue will be collected from the lower abdominal region under local anesthesia. The extracted tissue will be processed to isolate and expand MSCs.

Infusion Phase: Participants will receive either DT2-SCT (1 x 10^6 cells/kg) or placebo in a 100 mL Plasma-Lyte solution via intravenous infusion over one hour. Safety will be monitored during and after the infusion.

Follow-Up Visits: Participants will be followed for six months, with evaluations at 7 days, 1 month, 3 months, and 6 months post-infusion. These visits include assessments of glycemic control, insulin resistance, adverse events, and overall health.

Objectives:

Primary Objective: To determine the safety and tolerability of a single intravenous dose of DT2-SCT in T2DM patients.

Secondary Objectives:

Assess changes in insulin resistance using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR).

Evaluate changes in fasting blood glucose (FBG) and HbA1c levels compared to baseline.

Measure the reduction in insulin and oral glucose-lowering drug dosages.

Methodology:

The MSCs used in DT2-SCT are self-renewing, multipotent cells with documented capacity for differentiation into various cell types, including pancreatic β-cells. The mechanism of action includes immunomodulation, anti-inflammatory effects, and potential enhancement of β-cell regeneration. These properties suggest that DT2-SCT could address both insulin resistance and β-cell dysfunction in T2DM.

Statistical Considerations:

The sample size of 120 participants is designed to provide robust safety data and meaningful descriptive results for efficacy. An interim safety analysis will be conducted after the first 20 participants complete their 3-month follow-up.

Inclusion criteria

• Adults (male or female) between ages of 30 - 75 years
• Should have Type 2 diabetes mellitus
• With Insulin requirement of 0.7 IU/kg/d or 50 IU/d, whichever is lesser
• Glutamic acid decarboxylase (GAD) antibody status should be negative
• Body Mass Index (BMI) 19 - 30 kg/m2
• Fasting blood glucose (FBG) should be ≥ 7.0 mmol/L, and HbAc1 ≥ 7%
• Intravenous insulin tolerance tests (ITT) indicate a patient's insulin resistance
• Should be ambulatory and in good general health
• Willing and able to comply with the study procedures and visit schedules and able to follow verbal and written instructions
• Willing to abstain from the use of protocol-restricted treatments from Screening through the End-of-Treatment
• No clinically significant abnormalities observed in medical history, physical exam vital signs, and laboratory assessments
• For females with reproductive potential: Should agree to use effective contraception for at least 1 month prior to screening and should agree to use such a method till end of the study period and negative pregnancy test
• For males with reproductive potential: should use condoms and other methods to ensure effective contraception with a partner

Exclusion criteria

• Subjects with Type 1 Diabetes Mellitus (T1DM) or secondary diabetes
• Subjects with serum creatinine 1.5 mg/dl or higher
• Abnormal liver function test (defined as value of transaminases > 3 times the upper limit of normal or serum bilirubin higher than normal for the reference value for the laboratory)
• History of myocardial infarction or unstable angina in previous 3 months
• History of malignancy or current malignancy other than non-melanomatous skin cancer
• Subjects with active infections
• Subject with serious medical conditions other than cardiovascular disease
• Subject with, or with a medical history of auto-immune diseases
• Subject with a medical history of mental disorder or epilepsy
• Subject abuse alcohol 10 times a week or smoke 25 cigarettes a day
• Subject who was diagnosed with cancer within 5 years before screening
• Subject who participated in another clinical trial within 6 months prior to the screening of this clinical trial
• Subject who was administered with immunosuppressants such as cyclosporin A or azathioprine within 6 weeks prior to the screening
• Serious life-threatening conditions
• Allergies to anesthesia
• Subject who is pregnant or nursing
• Subject is on chronic immunosuppressive transplant therapy
• Subjects who tested positive for HIV 1/2, HBV, HCV, HTLV I/II, WNV, and syphilis
• Flu symptoms
• Any past history of lipid disorders: lipedema, lipomatosis, or lipodystrophies
• Active cancer, chemotherapy, or other malignancies in the last 6 months prior to the screening
• Any past history of DVT or pulmonary embolism requiring anticoagulants or other medicines
• Requiring supplemental oxygen
• Major surgeries within 6 months prior to the screening
• Wounds/sepsis ongoing or within 3 months prior to the screening
• Any illness which in the Investigator's judgment, may interfere with the subject's ability to comply with the protocol, compromise patient safety, or interfere with the interpretation of the study results