Islet Cell Transplants for Diabetes

NCT00303134 | Terminated Phase 1

• 1 other identifier: 0105004956
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Diabetes Mellitus, Type 1

Keywords

islet cell; diabetes; transplant; immunosuppression; autoimmunity; alloimmunity

Outcome Measures

Primary Outcomes (1)

• Insulin independence 12 months after final islet infusion

Secondary Outcomes (6)

• Basal c-peptide level

• Hemoglobin A1c level

• Glucose tolerance

• C-peptide response to arginine

• Mean Amplitude of Glucose Excursion (MAGE)

Study Arms (1)

Islet Cell Transplantation

EXPERIMENTAL

Drug: Islet Cell Transplantation

Interventions

Islet Cell Transplantation DRUG

Islet Cell Transplantation for patients with type 1 diabetes mellitus

Islet Cell Transplantation

Eligibility Criteria

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

You may qualify if:

• \- 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).

You may not qualify if:

• 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.
• 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.
• 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.)
• History of non-adherence to prescribed regimens
• Active infection including hepatitis C, hepatitis B, HIV, or TB (or under treatment for suspected TB)
• Any history of or current malignancies except squamous or basal skin cancer
• BMI \> 26 kg/m2
• 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)

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

New York Presbyterian Hospital - Weill Cornell Medical Center

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Autoimmune Diseases

Interventions

Islets of Langerhans Transplantation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Meredith J Aull, Pharm.D.

  New York Presbyterian Hospital - Weill Cornell 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: March 13, 2006
• First Posted: March 15, 2006
• Study Start: August 1, 2003
• Primary Completion: October 23, 2007
• Study Completion: June 24, 2010
• Last Updated: June 3, 2019

Record last verified: 2019-05

Locations

US (1)