Islet After Kidney Transplantation (IAK) in Patients With Type 1 Diabetes

NCT00708604 | Completed Phase 1 DMC

• 2 other identifiers: 04033DK56952
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety of islet transplantation in patients with type 1 diabetes who have had a successful kidney transplant and have been maintained for at least three months on anti-rejection medications consisting of any combination of sirolimus, tacrolimus, MMF or prednisone (5 mg/day or less). Another purpose is to determine the effectiveness of an islet transplant in inducing insulin independence and whether or not an islet transplant improves quality of life for kidney transplants patients with type 1 diabetes.

Conditions

Diabetes Mellitus

Keywords

Diabetes Mellitus; Kidney Transplantation; Islet Transplantation; Sirolimus/Tacrolimus/MMF-based Immunosuppressive Regimen

Outcome Measures

Primary Outcomes (1)

• Percent of subjects who have achieved insulin sufficiency post transplant.

  3, 6, 12, and 24 months

Secondary Outcomes (4)

• Stimulated C-peptide response >0.6 ng/ml

  3, 6, 12, and 24 months

• Insulin use </= 0.2 units/kg/day

  3, 6, 12, and 24 months

• Reduction/elimination of hypoglycemic episodes

  3, 6, 12, and 24 months

• HgAlc</= 6.5%

  3, 6, 12, and 24 months

Study Arms (1)

1

EXPERIMENTAL

Islet transplantation

Procedure: Islet Transplantation; Biological: Islet cell transplantation

Interventions

Islet Transplantation PROCEDURE

Islet Transplantation

1

Islet cell transplantation BIOLOGICAL

Islet cell transplantation will occur through the portal vein.

1

Eligibility Criteria

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

You may qualify if:

• Type 1 diabetes mellitus. Documentation of negative basal and stimulated C-peptide (a basal level of \</= 0.2 ng/ml before IV administration of 1 mg of glucagon, and a glucagon stimulated C-peptide \</= 0.8 ng/ml) and diagnosis of diabetes for at least 5 years.
• Recipient of renal transplant with good function (serum creatinine \</= 1.6 mg/dl, creatinine clearance \>/=60 ml/min and albumin excretion \</= 300 mg/24 hr) for \>3 months.
• Stable immunosuppression consisting of any combination of sirolimus, tacrolimus, MMF or \</= 5 mg/day of corticosteroids for at least 3 months, without major complications.
• No history of acute rejection episodes related to renal graft in last 12 months and low risk for developing acute rejection (first renal transplant, PRA \<25%, negative kidney crossmatch by B, T, flow cytometry)
• Under the continuing care of a renal transplant nephrologist/surgeon.
• No evidence of liver disease (liver enzymes \< twice the upper limit of normal for each of ALT and AST, bilirubin \< 2 mg/dl, albumin \> 3.5 g/dl, and PT and PTT \</= 1.1 x the upper limit of normal).
• Ability to comply with post-transplant regimen, including immunosuppression, insulin pump therapy and metabolic testing. Patients will be required to perform self-monitoring of blood glucose a minimum of four times daily, and provide complete records of blood glucose levels and insulin doses.
• Ability to give informed consent.
• Age greater than or equal to 18 years or less than or equal to 65 years.
• Subjects that have always been managed on a sirolimus/tacrolimus/MMF/low-dose corticosteroid (\</=5mg) immunosuppressive regimen and never required conversion must provide a signed letter from their transplant nephrologist /surgeon documenting this.
• Subjects converted to a sirolimus/tacrolimus/MMF/low-dose corticosteroid immunosuppressive regimen, must provide proof of informed consent regarding immunosuppressive conversion in one of the following formats.
• Subjects that converted to sirolimus/tacrolimus/MMF/low-dose corticosteroids (\</=5mg) due to best patient care (not to qualify for islet transplantation) must provide a signed letter from their transplant nephrologists/surgeon indicating the medical reason(s) for immunosuppression conversion (with the date indicated).
• Subjects that converted to a sirolimus/tacrolimus/MMF/low-dose corticosteroid (\</=5mg) immunosuppressive regimen for the purpose of qualifying for islet transplantation must provide a signed immunosuppression conversion consent form.

You may not qualify if:

• Poor renal allograft function (serum creatinine \> 1.6 mg/dl, creatinine clearance \< 60ml/min, albumin excretion \>300 mg/24hr)
• History of acute rejection related to renal graft in last 12 months or "high risk" for acute rejection (more than one previous renal transplant, PRA \>25%, positive kidney crossmatch by B, T, flow cytometry)
• Current immunosuppression therapy with corticosteroids \>5mg/day.
• Significant liver disease (including elevation of liver enzymes \> twice the upper limit of normal for each of ALT and AST, bilirubin \> 2 mg/dl, albumin \< 3.5 g/dl, liver masses including portal vein thrombosis, evidence of portal hypertension, or significant, untreated gallbladder disease (i.e., gallstones).
• Significant cardiovascular disease, including non-correctable coronary artery disease with ejection fraction \< 50% and/or recent myocardial infarction (within last 12 months); extensive peripheral vascular disease not correctable by surgery or untreated proliferative retinopathy.
• Recent unresolved acute infection, or chronic infection, including tuberculosis, HIV, HBV, HCV, CMV or positive skin test for TB.
• Any history of malignancy, except squamous or basal skin cancer or in situ cancer of the cervix.
• Recent history of non-compliance, or inability to demonstrate capacity to comply with strict blood glycemic control and insulin pump therapy.
• Psychiatric illness that is untreated, or likely to interfere significantly with transplantation despite treatment.
• Presence of preformed antibodies on panel reactive antibody screening \> 25%.
• Body mass index (BMI) greater than 30.
• Age less than 18 years or greater than 65 years.
• Presence of a chronic disease that must be chronically treated with one or more of the following medications: glucocorticoids, diazoxide, bumetanide, haloperidol, chlorpromazine, desipramine, doxepin, imipramine, levodopa, morphine, L-asparaginase, cyclophosphamide, isoniazid, heparin, nalidixic acid, or any other agents that may adversely influence glycemic control and which may confound the interpretation of Graft Success post-transplant.
• Pregnant women, women intending future pregnancy, women of reproductive potential who are unable or unwilling to follow effective contraceptive measures for the duration of immunosuppressive therapy, and women presently breast feeding are ineligible due to the unknown effects of these drugs on the fetus and nursing infant.
• Active alcohol or substance abuse, including cigarette smoking (must be abstinent for \> 3 months).

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Related Publications (4)

• Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000 Jul 27;343(4):230-8. doi: 10.1056/NEJM200007273430401.

  PMID: 10911004 BACKGROUND

• Ryan EA, Paty BW, Senior PA, Bigam D, Alfadhli E, Kneteman NM, Lakey JR, Shapiro AM. Five-year follow-up after clinical islet transplantation. Diabetes. 2005 Jul;54(7):2060-9. doi: 10.2337/diabetes.54.7.2060.

  PMID: 15983207 BACKGROUND

• Fiorina P, Folli F, Maffi P, Placidi C, Venturini M, Finzi G, Bertuzzi F, Davalli A, D'Angelo A, Socci C, Gremizzi C, Orsenigo E, La Rosa S, Ponzoni M, Cardillo M, Scalamogna M, Del Maschio A, Capella C, Di Carlo V, Secchi A. Islet transplantation improves vascular diabetic complications in patients with diabetes who underwent kidney transplantation: a comparison between kidney-pancreas and kidney-alone transplantation. Transplantation. 2003 Apr 27;75(8):1296-301. doi: 10.1097/01.TP.0000061788.32639.D9.

  PMID: 12717219 BACKGROUND

• Fiorina P, Folli F, Zerbini G, Maffi P, Gremizzi C, Di Carlo V, Socci C, Bertuzzi F, Kashgarian M, Secchi A. Islet transplantation is associated with improvement of renal function among uremic patients with type I diabetes mellitus and kidney transplants. J Am Soc Nephrol. 2003 Aug;14(8):2150-8. doi: 10.1097/01.asn.0000077339.20759.a3.

  PMID: 12874470 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Islets of Langerhans Transplantation

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Endocrine Surgical Procedures; Surgical Procedures, Operative; Transplantation

Study Officials

• Fouad Kandeel, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2008
• First Posted: July 2, 2008
• Study Start: October 18, 2008
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: April 27, 2026

Record last verified: 2014-07

Locations

US (1)