Pancreatic Islets and Parathyroid Gland Co-transplantation for Treatment of Type 1 Diabetes

NCT03977662 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 18-26725
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (4)

• 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

Secondary Outcomes (5)

• Glycemic control

  Day 75, Day 180, Day 270, Year 1, Year 1.5, Year 2

• Hypoglylcemic episodes: Clarke Survey Score

  Day 75, Day 180, Day 270, Year 1

• Hypoglylcemic episodes: Hypo Score

  Day 75, Day 180, Day 270, Year 1

• Beta cell function as assessed by Mixed Meal Tolerance Test (MMTT)

  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)

  Day 75, Day 180, Day 270, Year 1, Year 1.5, Year 2

Study Arms (1)

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

Combination Product: Co-transplantation of PTG with pancreatic islets

Interventions

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

PTG with adult pancreatic islet co-transplantation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects age 18 or older.
• Subjects who are able to provide written informed consent and to comply with study procedures.
• Clinical history compatible with Type 1 diabetes (onset \< 40 yrs old and insulin dependent for \> 5 yrs at enrollment, c-peptide negative).
• Recipients should have absent stimulated c-peptide (\< 0.3 ng/mL) in response to a (Boost® 6 mL/kg BW to a maximum of 360 mL; another equivalent product), measured at 60 and 90 min after start of consumption.
• Subjects who are \> 6 months post-renal transplant or \>6 months post-liver transplant who are taking appropriate calcineurin inhibitor (CNI) based maintenance immunosuppression (\[tacrolimus alone or in conjunction with sirolimus, mycophenolate mofetil, myfortic, or azathioprine; or cyclosporine in conjunction with sirolimus, mycophenolate mofetil, or myfortic ± Prednisone ≤ 10 mg/day).
• Stable renal function as defined by a creatinine of no more than one third greater than the average creatinine determination performed in the 6 previous months prior to islet transplant, as well as absence of a rejection episode in the 6 months prior to islet transplant
• Stable 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 absence of a rejection episode in the 6 months prior to islet transplant

You may not qualify if:

• 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:

Sponsors & Collaborators

• Peter Stock: lead
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (1)

University of California

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Peter Stock, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: May 24, 2019
• First Posted: June 6, 2019
• Study Start: July 1, 2019
• Primary Completion: January 31, 2026
• Study Completion: January 31, 2026
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

US (1)