Pancreatic Islets and Parathyroid Gland Co-transplantation for Treatment of Type 1 Diabetes
Pancreatic Islets and Parathyroid Gland Co-transplantation for Treatment of Type 1 Diabetes
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.
Inclusion Criteria:

 1. Male and female subjects age 18 to 70 years of age.

 2. Subjects who are able to provide written informed consent and to comply with study
 procedures.

 3. Clinical history compatible with Type 1 diabetes (onset < 40 yrs old and insulin
 dependent for > 5 yrs at enrollment, c-peptide negative).

 4. 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.

 5. 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).

 6. 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

 7. 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:

 1. 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

 2. Insulin requirement of >1.0 IU/kg/day

 3. Weight more than 100 kg or body mass index (BMI) > 30 kg/m2.

 4. Primary hyperparathyroidism OR secondary hyperparathyroidism

 5. Untreated or unstable proliferative diabetic retinopathy.

 6. Blood Pressure: SBP > 180 mmHg or DBP >100 mmHg despite treatment with
 antihypertensive agents.

 7. 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

 8. 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

 9. Proteinuria (albumin/creatinine ratio or ACr > 300mg/g) of new onset since kidney
 transplantation.

 10. 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.

 11. Active infection including hepatitis B, hepatitis C, HIV, or TB. A positive skin test
 (PPD) in itself is not an exclusion and will be followed up by a Quantiferon gold
 assay.

 12. Negative screen for EBV IgG.

 13. Invasive aspergillus, histoplasmosis, and coccidioidomycosis infection within 1 year
 prior to study entry.

 14. Any history of malignancy following receiving either the kidney or liver transplant,
 except for completely resected squamous or basal cell carcinoma of the skin

 15. Known active alcohol or substance abuse.

 16. Severe co-existing cardiac disease, characterized by any one of these conditions:

 1. Recent MI (within past 6 months),

 2. Evidence of ischemia on functional cardiac exam within the last year,

 3. Left ventricular ejection fraction < 30%,

 4. Valvular disease requiring replacement with prosthetic valve.

 17. Active infections (except mild skin and nail fungal infections).

 18. Active peptic ulcer disease or gastritis, symptomatic gallstones, or portal
 hypertension.

 19. Use of any investigational agents within 4 weeks of enrollment.

 20. Administration of live attenuated vaccine(s) within 2 months of enrollment.

 21. Any medical condition that, in the opinion of the investigator, will interfere with
 safe study completion.

 22. Positive screen for BK viremia at time of screening.

 23. Untreated hyperlipidemia - TC > 200 mg/dL, TGC > 200 mg/dL, LDL > 130 mg/dL