Islet Cell Transplants for Diabetes

This study has suspended participant recruitment.
Sponsor:
Information provided by:
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00303134
First received: March 13, 2006
Last updated: December 4, 2008
Last verified: September 2007
  Purpose

The purpose of this study is to test the safety and efficacy of islet cell transplants for the treatment of type 1 diabetes mellitus. It has been shown that normal control of blood sugar levels can prevent progression of complications (such as kidney disease, nerve damage, and vascular disease) from diabetes. This research study is designed to see if normal blood sugar control can be achieved by transplanting pancreatic islet cells into your liver, which may reduce or eliminate your need for insulin. Patients may qualify to participate in this research study if they have type 1 diabetes mellitus for at least five years and meet at least one of the following criteria:

  • Experience hypoglycemic unawareness - Defined as inability to tell when blood glucose is low (for example, may not feel symptoms such as shaking, sweating, and rapid heartbeat that usually signify that glucose is low)
  • Have been hospitalized several times in the past year for low blood sugar and/or high blood sugar
  • Have complications of diabetes such as retinopathy, kidney problems, or neuropathy

Condition Intervention Phase
Diabetes Mellitus, Type 1
Procedure: Islet Cell Transplantation
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Human Islet Cell Transplantation in Type 1 Diabetic Patients

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • Insulin independence 12 months after final islet infusion

Secondary Outcome Measures:
  • Basal c-peptide level
  • Hemoglobin A1c level
  • Glucose tolerance
  • C-peptide response to arginine
  • Mean Amplitude of Glucose Excursion (MAGE)
  • Mixed meal test

Estimated Enrollment: 8
Study Start Date: August 2003
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- Enrolling subjects must have Type 1 diabetes mellitus for more than 5 years, complicated by at least one of the following situations that persist despite intensive insulin management efforts. (Intensive management is defined as monitoring of glucose values at home no less than three times each day and by the administration of three or more insulin injections each day. Such management must be monitored in close cooperation with an endocrinologist or primary care physician, as defined by at least three contacts during the previous 12 months. If an endocrinologist did not participate in the ongoing management effort during the past year, then an independent endocrinologist must assess the adequacy of the management efforts prior to enrollment.) The complicating situations are:

a. Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at plasma glucose levels of < 54 mg/dL, b. Metabolic lability/instability, characterized by two or more episodes of severe hypoglycemia and which is associated with a blood glucose below 54 mg/dl OR two or more hospital visits for diabetic ketoacidosis over the last year, c. Despite efforts at optimal glucose control, progressive secondary complications of diabetes as defined by: i) Retinopathy—a minimum of a three step progression using the Early Treatment Diabetic Retinopathy Study (ETDRS) grading system 44,or an equivalent progression as certified by an ophthalmologist familiar with diabetic retinopathy, or ii) Nephropathy—a confirmed rise of 50 µg/min (72 mg/24h) of microalbuminuria or greater over at least three months (beginning anytime within the past two years) despite the use of an ACE inhibitor, or iii) Neuropathy—persistent or progressing autonomic neuropathy (gastroparesis, postural hypotension, neuropathic bowel or bladder) or persistent or progressing severe peripheral painful neuropathy not responding to usual management (e.g., tricyclics, gabapentin, or carbamazepine).

Exclusion Criteria:

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

    • Recent myocardial infarction (within past six months), or
    • Angiographic evidence of non-correctable coronary artery disease, or
    • Evidence of ischemia on functional cardiac exam (functional testing is required for all subjects, with a stress echo test recommended for subjects with a history of ischemic disease). Patients unable to perform an exercise stress echocardiogram test will undergo adenosine vasodilator stress test, and if there is a history of bronchospasm, will undergo dobutamine stress test.
  2. Active alcohol or substance abuse-includes cigarette smoking (must be abstinent for six months). Active alcohol abuse should be considered using the current NIAAA definitions, whereby alcohol abuse is defined by a pattern of drinking that is accompanied by one or more of the following situations within a 12-month period:

    • Failure to fulfill major work, school, or home responsibilities;
    • Drinking in situations that are physically dangerous, such as while driving a car or operating machinery;
    • Recurring alcohol-related legal problems, such as being arrested for driving under the influence of alcohol or for physically hurting someone while drunk;
    • Continued drinking despite having ongoing relationship problems that are caused or worsened by the effects of alcohol.
  3. Psychiatric disorder making the subject not a suitable candidate for transplantation, e.g., schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medication. (A psychological or psychiatric consultation is required only if considered necessary by some current indication or history.)
  4. History of non-adherence to prescribed regimens
  5. Active infection including hepatitis C, hepatitis B, HIV, or TB (or under treatment for suspected TB)
  6. Any history of or current malignancies except squamous or basal skin cancer
  7. BMI > 26 kg/m2
  8. C-peptide response to arginine stimulation (5 gm I.V.) (any C-peptide ≥ 0.3 ng/mL at 2, 3, 4, 5, 7 and 10 min post-infusion)
  9. Inability to provide informed consent
  10. Age less than 18 or greater than 65 years
  11. Creatinine clearance <80 mL/min/1.73 m2
  12. Serum creatinine >1.6 mg/dL
  13. Macroalbuminuria (urinary albumin excretion rate >300 mg/24h)
  14. Baseline Hb <10.5 gm/dL in women, or <13 gm/dL in men
  15. Baseline LFT's outside of normal range with the exception of Gilberts Syndrome. (An initial LFT test panel with any values >1.5 times upper limits of normal will exclude a patient; a re-test for any values between normal and 1.5 times normal should be made, and if the values remain elevated above normal limits, the patient will be excluded.)
  16. Presence of gallstones (subjects may be eligible two weeks after a laparoscopic cholecystectomy)
  17. Portal hypertension, detected by baseline duplex ultrasonography (assessment of direction of flow in right, left and main portal vein [antegrade (normal) or retrograde (abnormal indicative of portal hypertension)]; hemangioma in liver on baseline ultrasonography
  18. Untreated proliferative retinopathy
  19. Positive pregnancy test, intent for future pregnancy or male subjects' intent to procreate, failure to follow effective contraceptive measures, or presently breast-feeding
  20. Evidence of sensitization on PRA (determined by demonstration of positive results for anti-HLA antibodies using solid phase immunoassay with soluble HLA Class I molecules as a target, or a general PRA panel with reactivity >20%)
  21. Insulin requirement >0.7 IU/kg/day
  22. HbA1C >12%
  23. Inability to reach the study hospital for transplantation within 24 hrs of notification
  24. Untreated hyperlipidemia (fasting LDL cholesterol >130 mg/dL and/or fasting triglycerides >200 mg/dL)
  25. Treated hyperlipidemia that is uncontrolled (fasting LDL cholesterol >130 mg/dL; and/or fasting triglycerides >200 mg/dL)
  26. Under treatment for a medical condition requiring chronic use of steroids aa. Use of coumadin or other anticoagulant therapy (except aspirin) or subject with PT/INR >1.5

    27. Addison's disease. All subjects should be screened with a basal 8:00 a.m. cortisol test. Results less than the lower limit of normal indicate further testing (e.g., a Cortrosyn stimulation test) to rule out adrenal insufficiency. Abnormal ACTH stimulation test will be an exclusion criterion.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00303134

Locations
United States, New York
New York Presbyterian Hospital - Weill Cornell Medical Center
New York, New York, United States, 10021
Sponsors and Collaborators
Weill Medical College of Cornell University
Investigators
Study Director: Dolca A Thomas, M.D. New York Presbterian Hospital - Weill Cornell Medical Center
Principal Investigator: Manikkam Suthanthiran, M.D. New York Presbyterian Hospital - Weill Cornell Medical Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00303134     History of Changes
Other Study ID Numbers: 0105004956
Study First Received: March 13, 2006
Last Updated: December 4, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:
islet cell
diabetes
transplant
immunosuppression
autoimmunity
alloimmunity

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014