Screening of Subjects With Type I Diabetes to Determine Eligibility for Islet Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Miami
Sponsor:
Information provided by (Responsible Party):
Rodolfo Alejandro, University of Miami
ClinicalTrials.gov Identifier:
NCT02004964
First received: November 25, 2013
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

Protocol to screen potential subjects for islet transplantation


Condition
Type 1 Diabetes Mellitus

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Screening of Subjects With Type I Diabetes to Determine Eligibility for Islet Transplantation

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • eligibility for islet transplantation [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    This trial has the objective to determine subject eligibility for future islet transplant trials using fasting labs (including CBC, Chemistry, PRA, auto-antibodies, coagulation panel and others); a mixed meal tolerance test, psychological evaluation and a physical exam.


Estimated Enrollment: 600
Study Start Date: April 2009
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Detailed Description:

Subjects with Type 1 diabetes and history of severe hypoglycemia will undergo screening similar to the screening done for islet transplantation including: history; physical; chest X rays; upper GI series if history of ulcer; abdominal and pelvic ultrasound with careful attention to liver parenchyma and gallbladder; EKG; stress echocardiography if older than 35, psychological evaluation; autonomic and sensorimotor evaluation. They will also have a tuberculosis skin test (PPD), and pre-transplant laboratory tests, including: serology (for hepatitis B and C, HTLV I and II, Herpesvirus 1 and 2, CMV, EBV, Parvovirus B19, RPR and HIV); first morning urine (albumin, protein and creatinine), GFR; urinalysis and urine culture; CBC, chemistry, PT, PTT, INR, C-peptide (basal and stimulated), HbA1c, , lipid profile, LFTs, thyroid profile, blood typing, PRA, MHC determination, auto-antibodies (GAD65, IA2 and insulin), and if male, prostate specific antigen (PSA). Severity of glucose lability and hypoglycemia unawareness is assessed with Clarke score, Lability index, Mage and hypoglycemia score.

I

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Subjects with type 1 DM

Criteria

Inclusion Criteria:

  1. Patients between 18 and 65 years of age
  2. Patients with type 1 diabetes mellitus for more than 5 years duration
  3. Body Mass Index (BMI)
  4. Fulfill one or more of the following:

1. Manifest signs and symptoms that are severe enough to be incapacitating. Incapacitating signs and symptoms include hypoglycemic episodes requiring assistance by others and hypoglycemia unawareness, (the inability to recognize low blood glucoses; glucoses <54 mg/dl); and/or 2. Patients with poor diabetes control (HbA1c > 8.0% but < 12%), despite intensive insulin therapy, as defined by: self monitoring of blood glucose ≥ 4 times/day, and multiple insulin injections (≥ 3/day) or insulin pump, and close monitoring of blood glucose control by an Endocrinologist.; and/or 3. Progressive diabetic complications.

Exclusion Criteria: Potential candidates will be excluded as per following criteria:

  1. Age <18 or >65 years;
  2. Duration of diabetes <5 years;
  3. Do not have a physician that is monitoring diabetes for > 6 months;
  4. Body Mass Index >30
  5. Weight >80 kg;
  6. Insulin requirement >1.0 u/kg/d;
  7. HbA1C >12%;
  8. Stimulated or basal C-peptide >0.3 ng/ml;
  9. Iohexol GFR<80
  10. Macroalbuminuria (>300 mg/24 hours);
  11. Anemia consistently lower than the normal range.
  12. Hyperlipidemia (fasting LDL cholesterol>130mg/dl and/or fasting triglycerides >200mg/dl);
  13. Abnormal liver function tests (consistently >1.5 x normal range);
  14. Serological evidence of HIV, HBsAg and/or HBcAb, HBsAb without history of vaccination, HTLV-1 or HCV;
  15. Negative serology for Epstein Barr virus (EBV) or evidence of acute or chronic infection (IgM≥IgG);
  16. Lack of updated immunizations per current CDC guidelines (including Lack of immunization against hepatitis B, pneumococcus and influenza - during season);
  17. Presence of panel reactive antibodies by flow cytometry
  18. Prostate specific antigen (PSA) >4 ng/ml unless malignancy ruled out;
  19. Positive tuberculin test (unless proof of adequate treatment can be provided);
  20. X-ray evidence of pulmonary infection or other significant pathology;
  21. Gall stones and/or portal hypertension and/or hemangioma on liver ultrasound;
  22. Abnormal abdominal or pelvic ultrasound (evidence of masses that are considered suspicious for malignancy or adenopathy);
  23. Active peptic ulcer disease;
  24. Active infections;
  25. Unstable cardiovascular status (including positive stress echocardiography if >age 35)/MI in the past 6 months/LVEF<30%)
  26. Untreated or unstable proliferative diabetic retinopathy;
  27. Previous/concurrent organ transplantation (except failed islet cell / pancreas transplantation);
  28. Malignancy or previous malignancy;
  29. Any medical condition requiring chronic use of steroids;
  30. Active alcohol or substance abuse; smoking in the last 6 months;
  31. Sexually active females who are not: a) post-menopausal, b) surgically sterile, or c) not using an acceptable method of contraception (oral contraceptives, Norplant, Depo-Provera, and barrier devices with spermicide are acceptable; condoms used alone are not acceptable);
  32. Positive pregnancy test or intent for future pregnancy, or male subject's intent to procreate;
  33. Any condition or any circumstances that makes it unsafe to undergo an islet cell transplant;
  34. Psychogenically unable to comply;
  35. Failed psychological evaluation.
  36. Persistent leukopenia (white blood cell count <3,000/uL on more than 3 occasions)
  37. Acute or chronic pancreatitis.
  38. Severe or unremitting diarrhea, vomiting or othe gastrointestinal disorder potentially interfering with the ability to absorb oral medications.
  39. Lymphopenia - < 1,000/uL 40 Neutropenia - <1,500/uL

41. Thrombocytopenia - <100,000/uL

  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: NCT02004964

Locations
United States, Florida
Diabetes Research Institute Recruiting
Miami, Florida, United States, 33136
Contact: Rodolfo Alejandro, MD    305-243-5321    islet@med.miami.edu   
Principal Investigator: Rodolfo Alejandro, MD         
Sponsors and Collaborators
Rodolfo Alejandro
Investigators
Principal Investigator: Rodolfo Alejandro, MD University of Miami
  More Information

Additional Information:
No publications provided

Responsible Party: Rodolfo Alejandro, Professor of Medicine, University of Miami
ClinicalTrials.gov Identifier: NCT02004964     History of Changes
Other Study ID Numbers: 20053135
Study First Received: November 25, 2013
Last Updated: June 5, 2014
Health Authority: United States: Institutional Review Board

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 July 22, 2014