Study of Islet Transplantation in Type 1 Diabetic Kidney Transplant Recipients

• ClinicalTrials.gov Identifier: NCT00888628
• Recruitment Status: Completed
• First Posted: April 27, 2009
• Results First Posted: January 27, 2017
• Last Update Posted: November 29, 2017
• Sponsor: Massachusetts General Hospital
• Collaborator: Boston Area Diabetes Endocrinology Research Center (funded by NIDDK)
• Information provided by (Responsible Party): James F. Markmann, MD, PhD, Massachusetts General Hospital

Study Description

Brief Summary:

The purpose of the study is to learn if islet transplantation is an effective treatment for Type 1 diabetes in people who have had a kidney transplant.

The primary objectives of the study are:

- To set up islet transplantation in patients who have had a kidney transplant and who are using an immunosuppressive regimen that works

The Secondary objective of the study is:

• To find out if successful islet transplantation leads to improved metabolic control and reduced renal complication from diabetes

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type I	Biological: Purified Pancreatic Islets; Drug: Etanercept	Phase 1; Phase 2

Detailed Description:

Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2doses of basiliximab.

All patients will receive Etanercept to promote engraftment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Islet Transplantation in Type 1 Diabetic Kidney Allograft Recipients
• Study Start Date: May 2009
• Actual Primary Completion Date: August 2014
• Actual Study Completion Date: August 2016

Arms and Interventions

Arm

Intervention/treatment

Experimental: Islet transplant; Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment.

Biological: Purified Pancreatic Islets; Islet after kidney transplant in patients with type I diabetes.; Drug: Etanercept; Given as induction for islet cell transplant

Outcome Measures

Primary Outcome Measures :

1. Insulin Independence With Both an HbA1c ≤ 6.5% and no Severe Hypoglycemic Events at 1 Year After the First Islet Transplant or a Reduction in HbA1c of at Least 1 Point and no Severe Hypoglycemic Events at 1 Year After the First Islet Transplant. [ Time Frame: 1 year after the subject's first islet transplant ]

Secondary Outcome Measures :

1. Number of Participants With a Decrease in HbA1c [ Time Frame: 1 year after subject's first islet transplant ]
   Subjects will have a decrease in HbA1c of at least >1%
2. Stable or Decrease in Urinary Albumin and Creatinine Ratio and Serum Creatinine [ Time Frame: 1 year after subjects initial islet transplant ]
   Proteinuria and serum creatinine will be stable or decreased as compared to pre-transplant values
3. An Absence Cardiovascular Events, Cerebral Vascular Accident, and Myocardial Infarction [ Time Frame: 1 year after the subject's first islet transplant ]
4. Impact on Vision [ Time Frame: 1 year after the subject's first islet transplant ]
   Improvement of frequency of interventions and from changes in reported visual acuity with optical refraction and severity of diabetic retinopathy
5. Absence of Negative Renal Impact Measures [ Time Frame: 1 year after the subject's first islet transplant ]
   Loss of allograft survivial (return to dialysis, retransplant, death) and Renal allograft function meausred by SCr
6. Improvement of Metabolic Control [ Time Frame: 1 year after the subject's first islet transplant ]

   Whether there is an improvement in metabolic control in IAK will be evaluated based on improvement in

   1. basal c-peptide levels,
   2. MMTT,
   3. insulin requirements, and
   4. c-peptide to glucose, creatinine ratio (CPGCR).
7. Number of Participants With a Decrease of Severe Hypoglycemic Events [ Time Frame: 1 year after subject's first transplant ]
   Subjects will have a decrease in severe hypoglycemic events
8. Reduction of Insulin Requriements [ Time Frame: 1 year after the subject's first islet transplant ]
   Evidence of partial success will be considered for subjects who have a reduction in insulin requirements but who are not insulin independent. This will be assessed by comparing the pre-transplant insulin requirement expressed as insulin units per kg per day with the requirement preceding subsequent islet transplants and the insulin requirements at 6 months and 1, 2, and 3 years after the first and last transplant.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male and female subjects
• Age 18 to 70 years of age
• Have insulin dependent Diabetes Mellitus Type 1
• Are post-renal transplant on maintenance immunosuppression with stable renal function
• HbA1c > 7.5% or < 7.5% and hypoglycemia unawareness

Exclusion Criteria:

• Weight more than 90 kg
• Insulin requirement > 60 Units/day
• Other (non-kidney) organ transplants except prior failed pancreatic graft.
• Untreated or unstable proliferative diabetic retinopathy
• Presence of de novo antibody production since the renal allograft or either Class I or Class II panel-reactive anti-HLA antibodies
• Active infection
• Negative screen for Epstein-Barr virus (EBV)
• Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin
• History of Factor V Leiden mutation
• Any coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g. warfarin) after transplantation (low-dose aspirin treatment is allowed) or subjects with international normalized ratio (INR) > 1.5
• Severe co-existing cardiac disease
• Persistent elevation of liver function tests at the time of study entry
• Acute or chronic pancreatitis
• Male subjects with elevation of prostate specific antigen
• Pregnancy
• Positive screen for polyoma (BK) virus
• Untreated hyperlipidemia
• Recent hemorrhagic stroke
• Factors associated with an increased risk of bleeding

Contact PI for complete Incl-Excl criteria list.

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Boston Area Diabetes Endocrinology Research Center (funded by NIDDK)

Investigators

• Principal Investigator: James F Markmann, MD, PhD; Massachusetts General Hospital

More Information

• Responsible Party: James F. Markmann, MD, PhD, Chief Division of Transplantation, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00888628
• Other Study ID Numbers: IAK
• First Posted: April 27, 2009
• Results First Posted: January 27, 2017
• Last Update Posted: November 29, 2017
• Last Verified: October 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by James F. Markmann, MD, PhD, Massachusetts General Hospital:

Type I diabetes; Islet after Kidney Transplant; Islet transplantation

Additional relevant MeSH terms:

Diabetes Mellitus, Type 1; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Etanercept; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Gastrointestinal Agents; Immunosuppressive Agents; Immunologic Factors