Clinical trial NCT04011020: Clinical Application of Stem Cell Educator Therapy in Type 1 Diabetes
Official title: Clinical Application of Stem Cell Educator Therapy in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Type 1 Diabetes
Lead sponsor: Throne Biotechnologies Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hackensack Meridian Health
First posted: 2019-07-08
Enrollment: 50
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Treatment group receive Stem Cell Educator therapy, control group receive conventional insulin therapy.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Adult patients ( 14 years)
2. Must have a diagnosis of type 1 diabetes mellitus based on the 2015 American Diabetes Association criteria for the Clarification and Diagnosis of diabetes.
3. Must have a blood test confirming the presence of at least one autoantibody to pancreatic islet Cells (IAA, IA2, GAD 65, ZnT8).
4. Fasting C-peptide level \> 0.3 ng/ml
5. HbA1C \< 10% at enrollment
6. Recent diagnosis (within two years of enrollment)
7. Adequate venous access for apheresis
8. Must be equipped with a continuous glucose monitoring system (CGMS)
9. Ability to provide informed consent
10. 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.
11. Must agree to comply with all study requirements and be willing to complete all study visits

Exclusion Criteria:

1. AST or ALT 2 \> x upper limit of normal.
2. Abnormal bilirubin (total bilirubin \> 1.2 mg/dL, direct bilirubin \> 0.4 mg/dL)
3. Creatinine \> 2.0 mg/dl.
4. Known coronary artery disease or EKG suggestive of coronary artery disease unless cardiac clearance for apheresis is obtained from a cardiologist.
5. Known active infection such as Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV)
6. Pregnancy assessed by a positive serum pregnancy test or breastfeeding mothers
7. Use of immunosuppressive medication within one month of enrollment including but not limited to prednisone, cyclosporine, tacrolimus, sirolimus, and chemotherapy.
8. Presence of any other autoimmune diseases (lupus, rheumatoid arthritis, scleroderma, etc.)
9. Anticoagulation other than ASA.
10. Hemoglobin \< 10 g/dl or platelets \< 100 k/ml
11. Is unable or unwilling to provide informed consent
12. Presence of any other physical or psychological medical condition that, in the opinion of the investigator, would preclude participation

Primary outcomes:
measure: Incidence of Treatment Adverse Events in T1D Subjects
timeFrame: 6 month
Secondary outcomes:
measure: Preliminary efficacy of SCE therapy to improve beta cell function
timeFrame: 12 months
measure: Preliminary efficacy of SCE therapy to improve glucose control
timeFrame: 12 months
measure: Preliminary efficacy of SCE therapy to reduce insulin dose
timeFrame: 12 months
measure: Efficacy of SCE therapy in immune modulation
timeFrame: 12 month
Other outcomes:
Locations:
city: Hackensack
country: United States
facility: Hackensack Meridian Health
state: New Jersey
city: Paramus
country: United States
facility: Throne Biotechnologies
state: New Jersey
Study officials:
affiliation: Throne Biotechnologies Inc.
name: YONG ZHAO, MD,PhD
role: STUDY_CHAIR
References:
citation: Zhao Y, Knight CM, Jiang Z, Delgado E, Van Hoven AM, Ghanny S, Zhou Z, Zhou H, Yu H, Hu W, Li H, Li X, Perez-Basterrechea M, Zhao L, Zhao Y, Giangola J, Weinberg R, Mazzone T. Stem Cell Educator therapy in type 1 diabetes: From the bench to clinical trials. Autoimmun Rev. 2022 May;21(5):103058. doi: 10.1016/j.autrev.2022.103058. Epub 2022 Jan 31.
citation: Zhao Y, Jiang Z, Zhao T, Ye M, Hu C, Yin Z, Li H, Zhang Y, Diao Y, Li Y, Chen Y, Sun X, Fisk MB, Skidgel R, Holterman M, Prabhakar B, Mazzone T. Reversal of type 1 diabetes via islet beta cell regeneration following immune modulation by cord blood-derived multipotent stem cells. BMC Med. 2012 Jan 10;10:3. doi: 10.1186/1741-7015-10-3.
citation: Zhao Y. Stem cell educator therapy and induction of immune balance. Curr Diab Rep. 2012 Oct;12(5):517-23. doi: 10.1007/s11892-012-0308-1.
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citation: Zhao Y, Jiang Z, Delgado E, Li H, Zhou H, Hu W, Perez-Basterrechea M, Janostakova A, Tan Q, Wang J, Mao M, Yin Z, Zhang Y, Li Y, Li Q, Zhou J, Li Y, Martinez Revuelta E, Maria Garcia-Gala J, Wang H, Perez-Lopez S, Alvarez-Viejo M, Menendez E, Moss T, Guindi E, Otero J. Platelet-Derived Mitochondria Display Embryonic Stem Cell Markers and Improve Pancreatic Islet beta-cell Function in Humans. Stem Cells Transl Med. 2017 Aug;6(8):1684-1697. doi: 10.1002/sctm.17-0078. Epub 2017 Jul 7.