Clinical Application of Stem Cell Educator Therapy in Type 1 Diabetes
- Conditions
- Type 1 Diabetes
- Interventions
- Combination Product: Stem Cell Educator therapy
- Registration Number
- NCT04011020
- Lead Sponsor
- Throne Biotechnologies Inc.
- Brief Summary
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that causes a deficit of pancreatic islet beta cells. Millions of individuals worldwide have T1D, and incidence increases annually. Several recent clinical trials point to the need for an approach that produces comprehensive immune modulation at both the local pancreatic and systemic levels. Stem Cell Educator (SCE) therapy offers comprehensive immune modulation at both the local and systemic levels in T1D by using a patient's own immune cells (including platelets) that are "educated" by cord blood stem cells. Tested clinically in more than 200 patients, SCE therapy has shown lasting reversal in autoimmunity in T1D patients, including improved C-peptide levels, reduced median glycated hemoglobin A1C (HbA1C) values, and decreased median daily usage of insulin. SCE therapy circulates a patient's blood through a blood cell separator, briefly cocultures the patient's immune cells with adherent Cord Blood Stem Cells (CB-SCs) in vitro, and returns the "educated" autologous immune cells to the patient's circulation.
- Detailed Description
The SCE device is made of a hydrophobic material from FDA-approved (USP Class VI) dishes that tightly binds stem cells CB-SCs without interfering with their immune modulating capability. We originally designed a chamber for co-culture of lymphocytes and CB-SCs that included nine discs of the material with a flow pathway and adherent CB-SCs sandwiched between a top cover plate and a bottom collecting plate. In this trial, we are going to use the 12-layer SCE device.
The SCE therapy carried a lower risk of infection than a typical blood transfusion, and did not introduce stem cells or reagents into the patients. In addition, CB-SCs have very low immunogenicity, and the CB-SCs cultured in the device are a highly restricted population and contain no CD3+ T cells or other lymphocyte subsets, eliminating the need for human leukocyte antigen (HLA) matching prior to treatment. This innovative approach has the potential to provide CB-SC-mediated immune modulation therapy for multiple autoimmune diseases while mitigating the safety and ethical concerns associated with other approaches such as T1D, type 2 diabetes (T2D), and alopecia areata (AA) in clinics. The relative simplicity of the approach may also provide cost and time savings relative to other approaches.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
- Adult patients ( 14 years)
- Must have a diagnosis of type 1 diabetes mellitus based on the 2015 American Diabetes Association criteria for the Clarification and Diagnosis of diabetes.
- Must have a blood test confirming the presence of at least one autoantibody to pancreatic islet Cells (IAA, IA2, GAD 65, ZnT8).
- Fasting C-peptide level > 0.3 ng/ml
- HbA1C < 10% at enrollment
- Recent diagnosis (within two years of enrollment)
- Adequate venous access for apheresis
- Must be equipped with a continuous glucose monitoring system (CGMS)
- Ability to provide informed consent
- For female patients only, willingness to use FDA-recommended birth control (http://www.fda.gov/downloads/ForConsumers/ByAudience/ForWomen/FreePublications/UCM356451.pdf) until 6 months post treatment.
- Must agree to comply with all study requirements and be willing to complete all study visits
- AST or ALT 2 > x upper limit of normal.
- Abnormal bilirubin (total bilirubin > 1.2 mg/dL, direct bilirubin > 0.4 mg/dL)
- Creatinine > 2.0 mg/dl.
- Known coronary artery disease or EKG suggestive of coronary artery disease unless cardiac clearance for apheresis is obtained from a cardiologist.
- Known active infection such as Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV)
- Pregnancy assessed by a positive serum pregnancy test or breastfeeding mothers
- Use of immunosuppressive medication within one month of enrollment including but not limited to prednisone, cyclosporine, tacrolimus, sirolimus, and chemotherapy.
- Presence of any other autoimmune diseases (lupus, rheumatoid arthritis, scleroderma, etc.)
- Anticoagulation other than ASA.
- Hemoglobin < 10 g/dl or platelets < 100 k/ml
- Is unable or unwilling to provide informed consent
- Presence of any other physical or psychological medical condition that, in the opinion of the investigator, would preclude participation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment of T1D with Stem Cell Educator therapy Stem Cell Educator therapy Recruited T1D subjects will receive one treatment with SCE therapy. Conventional insulin therapy Stem Cell Educator therapy Control group will receive conventional insulin therapy.
- Primary Outcome Measures
Name Time Method Incidence of Treatment Adverse Events in T1D Subjects 6 month The occurrence of treatment-related adverse events will be evaluated post the treatment with SCE therapy.
- Secondary Outcome Measures
Name Time Method Preliminary efficacy of SCE therapy to reduce insulin dose 12 months Change in daily insulin requirements
Preliminary efficacy of SCE therapy to improve beta cell function 12 months Preliminary efficacy as measured by Area under the C-peptide curve (AUC) over the first 2 hours of a 3-hour mixed meal tolerance test (MMTT)
Efficacy of SCE therapy in immune modulation 12 month Measurements of immune markers at baseline, 1, 3, 6, 9, and 12 months. Peripheral blood mononuclear cells (PBMC) will be collected and tested by flow cytometry.
Preliminary efficacy of SCE therapy to improve glucose control 12 months Change in HbA1C levels over time
Trial Locations
- Locations (2)
Throne Biotechnologies
🇺🇸Paramus, New Jersey, United States
Hackensack Meridian Health
🇺🇸Hackensack, New Jersey, United States