Klinisk anvendelse av stamcellepedagogterapi ved type 1-diabetes
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 300 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-SC) in vitro, and returns the "educated" autologous immune cells to the patient's circulation.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
The SCE device is made of a hydrophobic material from FDA-approved (USP Class VI) dishes that tightly binds stem cells CB-SC without interfering with their immune modulating capability. During SCE therapy, a patient's peripheral blood mononuclear cells (PBMC) are collected by leukapheresis and co-cultured with adherent cord-blood-derived multipotent stem cells (CB-SC) in vitro, after which the "educated" PBMC are returned to the patient's circulation via infusion. Over the last 15 years, this technology has been evaluated through international multicenter clinical studies conducted in the United States, China, and Spain. These studies have demonstrated the clinical safety and efficacy of SCE therapy in treating type 1 diabetes (T1D), alopecia areata (AA), and other autoimmune conditions, including reversal of T1D-associated autoimmunity and treatment of other immune dysfunction-associated diseases, such as alopecia areata, type 2 diabetes (T2D), Crohn's disease and long-COVID.
Studietype
Registrering (Antatt)
Fase
- Fase 3
Kontakter og plasseringer
Studiesteder
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New Jersey
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Paramus, New Jersey, Forente stater, 07652
- Throne Biotechnologies
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
- Pediatric and adult patients (>10 years).
- Must have a diagnosis of type 1 diabetes mellitus based on the American Diabetes Association (ADA) Guidelines.
- Must have a blood test confirming the presence of at least one autoantibody to pancreatic islet beta Cells (IAA, IA2, GAD 65, ZnT8).
- Fasting C-peptide level > 0.3 ng/ml.
- Adequate venous access for apheresis.
- Ability to provide informed consent or assent.
- 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.
Exclusion Criteria:
- 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, Human Immunodeficiency Virus (HIV), HTLV (human T-cell leukemia-lymphoma virus cAB), or active tuberculosis.
- Pregnant or breastfeeding women.
- 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 (Hashimoto's thyroiditis, celiac disease, lupus, rheumatoid arthritis, scleroderma, etc.).
- Anticoagulation other than ASA.
- Hemoglobin < 10 g/dl or platelets < 100 k/ml.
- Subjects with leukopenia, total white blood cells (WBC) count < 4000/uL.
- Patient or patient's surrogate is unable or unwilling to voluntarily sign an informed consent form.
- Presence of any other physical or psychological medical condition that, in the opinion of the investigator, would preclude participation.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Treatment of T1D with Stem Cell Educator therapy
Recruited T1D subjects will receive one treatment with SCE therapy. |
Patients with T1D will be evaluated by the study principal investigator or sub-investigators. Informed consent will be obtained at the initial screen meeting. Subjects who meet all criteria will be scheduled for treatment. All enrolled subjects will receive treatment with the Stem Cell Educator (SCE) therapy consisting of a single session of mononuclear cells (MNC) collection by apheresis where peripheral blood will be processed on day 1. The MNC product will then be exposed overnight to the SCE and on day 2 the product Gleukocell will be infused intravenously back to the patient. |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Change in fasting C-peptide levels
Tidsramme: 3 month
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Change in fasting C-peptide levels at Month 3 |
3 month
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Change in HbA1C levels
Tidsramme: 3 months
|
Change in HbA1C levels at Month 1 and Month 3 |
3 months
|
|
Change daily insulin requirement
Tidsramme: 3 months
|
Change daily insulin requirement at Month 1 and Month 3 |
3 months
|
|
Proportion of subjects achieving restoration of fasting C-peptide levels to the normal range
Tidsramme: 3 months
|
Proportion of subjects achieving restoration of fasting C-peptide levels to the normal range at Month 1 and Month 3 |
3 months
|
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Proportion of subjects achieving complete insulin independence
Tidsramme: 3 month
|
Proportion of subjects achieving complete insulin independence at Month 1 and Month 3 |
3 month
|
|
Changes in immune markers
Tidsramme: 3 month
|
Changes in regulatory T-cells and activated T-cells at Month 1 and Month 3 |
3 month
|
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Changes in immune markers
Tidsramme: 3 month
|
Changes in memory T-cells and naïve T-cells at Month 1 and Month 3 |
3 month
|
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Changes in immune markers
Tidsramme: 3 month
|
Changes in inflammatory chemokine CXCL16 at Month 1 and Month 3 |
3 month
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Studiestol: YONG ZHAO, MD,PhD, Throne Biotechnologies Inc.
Publikasjoner og nyttige lenker
Generelle publikasjoner
- 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.
- 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.
- 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.
- Delgado E, Perez-Basterrechea M, Suarez-Alvarez B, Zhou H, Revuelta EM, Garcia-Gala JM, Perez S, Alvarez-Viejo M, Menendez E, Lopez-Larrea C, Tang R, Zhu Z, Hu W, Moss T, Guindi E, Otero J, Zhao Y. Modulation of Autoimmune T-Cell Memory by Stem Cell Educator Therapy: Phase 1/2 Clinical Trial. EBioMedicine. 2015 Nov 5;2(12):2024-36. doi: 10.1016/j.ebiom.2015.11.003. eCollection 2015 Dec.
- 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.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 2019-TH-002
Plan for individuelle deltakerdata (IPD)
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Legemiddel- og utstyrsinformasjon, studiedokumenter
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