Islet transplantation for better blood sugar control in type 1 diabetes after kidney transplant

Islet Transplantation in Type 1 Diabetic Kidney Allograft

This study tests whether getting islet cells from donors after a kidney transplant can help people with type 1 diabetes control their blood sugar better without needing insulin shots.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 68 Years
• Sex: All
• Sponsor: University of Chicago (Academic / other)
• Drugs / interventions: Prednisone
• Locations: 1 site (Chicago, Illinois)
• Trial ID: NCT01241864 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and efficacy of islet transplantation performed after kidney transplantation in patients with type 1 diabetes. The islet cells, which produce insulin, are obtained from deceased donors and infused into the patients' portal vein. The goal is to achieve better blood sugar control without the need for insulin injections. Participants must be at least three months post-kidney transplant and meet specific criteria related to their diabetes condition.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 68 with a long history of insulin-dependent type 1 diabetes and who are at least three months post-kidney transplant.

Not a fit: Patients who are not insulin-dependent or those who have not undergone kidney transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve blood sugar management for patients with type 1 diabetes, reducing their reliance on insulin therapy.

How similar studies have performed: Previous studies have shown promise in islet transplantation, but this specific approach following kidney transplantation is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Male and female subjects age 18 to 68 years.
* Subjects who are able to provide written informed consent and to comply with the procedures of the study protocol.
* Clinical history compatible with T1D with disease onset \< 40 years of age and insulin-dependence for \> 5 years at the time of enrollment, and a sum of subject age and insulin dependent diabetes duration of \> 28.
* Absent stimulated c-peptide (\< 0.3 ng/mL) in response to a MMTT \[Boost® 6 mL/kg body weight (BW) to a maximum of 360 mL; another product with equivalent caloric and nutrient content may be substituted for Boost®\] measured at 60 and 90 min after start of consumption.
* Subjects who are \> or at 3 months post-renal 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)or subject will receive islets transplant within 72hours after kidney transplantation (islets and kidney are from the same donor)
* Stable renal function as defined by a creatinine of no more than one third greater than the average creatinine determination performed in the 3 previous months prior to islet transplantation, until rejection, obstruction or infection is ruled out.

Exclusion Criteria:

* Weight more than 90 kg or body mass index (BMI) \> 30 kg/m2.
* Insulin requirement of \>1.0 IU/kg/day or \<15 U/day.
* Other (non-kidney) organ transplants except prior failed pancreatic graft where the graft failed within the first two weeks due to thrombosis, followed by pancreatectomy; with the pancreas transplant occurring more than 6 months prior to enrollment.
* Untreated or unstable proliferative diabetic retinopathy.
* Blood Pressure: SBP \> 160 mmHg or DBP \>100 mmHg despite treatment with antihypertensive agents.
* Calculated GFR \< 40 mL/min/1.73 m2 using the subject's measured serum creatinine and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation \[1\]. Strict vegetarians (vegans) will be excluded only if their estimated GFR is \< 35 mL/min/1.73 m2
* Proteinuria (albumin/ creatinine ratio or ACr \> 300mg/g) of new onset since kidney transplantation.
* Either Class I or Class II panel-reactive anti-HLA antibodies \> 50%. Subjects with either Class I or Class II panel reactive anti-HLA antibodies \>50% will be excluded if any of the following are detected: Positive cross-match, Islet donor-directed 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, or Antibodies to the renal donor (i.e. presumed de novo).
* For female subjects: Positive pregnancy test, presently breast-feeding, desires to be pregnant at any time point in the future, which includes during or after the completion of the study even if study participation is ended early, 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.
* Presence or history of active infection including hepatitis B, hepatitis C, HIV, or tuberculosis (TB). Subjects with laboratory evidence of active infection are excluded even in the absence of clinical evidence of active infection.

Where this trial is running

Chicago, Illinois

• The University of Chicago — Chicago, Illinois, United States (Recruiting)

Study contacts

• Study coordinator: Lindsay Basto, RN, BSN

Conditions Diabetes Mellitus, Type 1