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| Name | Class |
|---|---|
| California Institute for Regenerative Medicine (CIRM) | OTHER |
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The primary objective is to test the hypothesis that co-transplantation of allogeneic PTG with adult pancreatic islets (derived from same deceased donor) in the IM site in people with Type 1 diabetes with functioning kidney and/or liver transplants is safe, allows islet engraftment, and leads to insulin independence.
Single-center, open label, non-randomized safety and efficacy trial to evaluate co-transplantation of allogeneic parathyroid glands (PTG) with adult pancreatic islets (both PTG and pancreatic islets obtained from same deceased donor) in people with Type 1 diabetes in the intramuscular (IM) site with stable function of liver or kidney allografts on chronic immunosuppression.
A total of 8 patients will be enrolled in the study and followed for a minimum of 1 year up to 2 years after the last islet transplant, depending on enrollment date.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PTG with adult pancreatic islet co-transplantation | Experimental | People with Type 1 (c-peptide negative) diabetes with stable kidney or liver allografts on chronic immunosuppression who receive study intervention, which is co-transplantation of allogeneic parathyroid (PTG) with adult pancreatic islets in people with Type 1 diabetes in the intramuscular (IM) site |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Co-transplantation of PTG with pancreatic islets | Combination Product | Co-transplantation of allogeneic parathyroid glands (PTG) with adult pancreatic islets (both PTG and pancreatic islets obtained from same deceased donor) in people with Type 1 diabetes in the intramuscular (IM) site with stable function of liver or kidney allografts on chronic immunosuppression |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events | Safety: Since this study is a pilot non-randomized safety and efficacy trial with patient enrollment limited by budgetary constraints, no direct statistical significance tests can be performed. | Minimum of 1 year up to 2 years depending on transplant date |
| Incidence of post-transplant infections and malignancies | Safety: Since this study is a pilot non-randomized safety and efficacy trial with patient enrollment limited by budgetary constraints, no direct statistical significance tests can be performed. | Minimum of 1 year up to 2 years depending on transplant date |
| Incidence of de novo sensitization | Safety: Since this study is a pilot non-randomized safety and efficacy trial with patient enrollment limited by budgetary constraints, no direct statistical significance tests can be performed. | Minimum of 1 year up to 2 years depending on transplant date |
| Incidence of Insulin independence | Efficacy: Incidence of participants no longer using insulin | Minimum of 1 year up to 2 years depending on transplant date |
| Measure | Description | Time Frame |
|---|---|---|
| Glycemic control | Assessed by measuring HbA1c using high-performance liquid chromatography | Day 75, Day 180, Day 270, Year 1, Year 1.5, Year 2 |
| Hypoglylcemic episodes: Clarke Survey Score | The Clarke survey will be used to assess the frequency and severity of hypoglycemic episodes |
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Inclusion Criteria:
Exclusion Criteria:
Presence of donor specific anti-HLA antibodies detected by Luminex Single Antigen/specificity bead assay including weakly reactive antibodies that would not be detected by a flow cross match
Insulin requirement of >1.0 IU/kg/day
Weight more than 100 kg or body mass index (BMI) > 30 kg/m2.
Primary hyperparathyroidism OR secondary hyperparathyroidism
Untreated or unstable proliferative diabetic retinopathy.
Blood Pressure: SBP > 180 mmHg or DBP >100 mmHg despite treatment with antihypertensive agents.
Calculated GFR of ≤ 40 mL/min/1.73 m2 using the subject's measured serum creatinine and the Chronic Kidney Disease Epidemiology Collaboration (CKD- EPI) equation, as well as presence of a rejection episode in the 6 months prior to islet transplant
Elevated liver function tests as defined by: SGOT (AST), SGPT (ALT), alkaline phosphatase values > 1.5, or total bilirubin >1.5 times normal upper limits at time of study entry, as well as presence of a rejection episode in the 6 months prior to islet transplant
Proteinuria (albumin/creatinine ratio or ACr > 300mg/g) of new onset since kidney transplantation.
For female subjects: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation. For male subjects: intent to procreate during the duration of the study or within 4 months after discontinuation or unwillingness to use effective measures of contraception. Oral contraceptives, Norplant®, Depo- Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable.
Active infection including hepatitis B, hepatitis C, HIV, or TB. Quantiferon gold assay will be used to determine TB infection.
Invasive aspergillus, histoplasmosis, and coccidioidomycosis infection within 1 year prior to study entry.
Any history of malignancy following receiving either the kidney or liver transplant, except for completely resected squamous or basal cell carcinoma of the skin
Known active alcohol or substance abuse.
Severe co-existing cardiac disease, characterized by any one of these conditions:
Active infections (except mild skin and nail fungal infections).
Use of any investigational agents within 4 weeks of enrollment.
Administration of live attenuated vaccine(s) within 2 months of enrollment.
Any medical condition that, in the opinion of the investigator, will interfere with safe study completion.
Positive screen for BK viremia at time of screening.
Untreated hyperlipidemia - TC > 200 mg/dL, TGC > 200 mg/dL, LDL > 130 mg/dL](streamdown:incomplete-link)
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| Name | Affiliation | Role |
|---|---|---|
| Peter Stock, MD, PhD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California | San Francisco | California | 94143 | United States |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 20, 2023 | Jun 17, 2024 | Prot_SAP_002.pdf |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| Day 75, Day 180, Day 270, Year 1 |
| Hypoglylcemic episodes: Hypo Score | The HYPO score will be used to assess the frequency and severity of hypoglycemic episodes | Day 75, Day 180, Day 270, Year 1 |
| Beta cell function as assessed by Mixed Meal Tolerance Test (MMTT) | Results from both MMTT and FSIGT will be used to assess beta cell function | Day 75, Day 180, Day 270, Year 1, Year 1.5, Year 2 |
| Beta cell function as assessed by Insulin-Modified Frequently-Sampled Intravenous Glucose ToleranceTest (FSIGT) | Results from both MMTT and FSIGT will be used to assess beta cell function | Day 75, Day 180, Day 270, Year 1, Year 1.5, Year 2 |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |