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

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.

Inclusion criteria

• 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

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:

• Recent MI (within past 6 months),
• Evidence of ischemia on functional cardiac exam within the last year,
• Left ventricular ejection fraction < 30%,
• Valvular disease requiring replacement with prosthetic valve.
• 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