Clinical trial NCT02004964: Screening of Subjects With Type I Diabetes to Determine Eligibility for Islet Transplantation
Official title: Screening of Subjects With Type I Diabetes to Determine Eligibility for Islet Transplantation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2013-12-09
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects with type 1 DM

Brief summary: Protocol to screen potential subjects for islet transplantation

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 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

Primary outcomes:
measure: eligibility for islet transplantation
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: Diabetes Research Institute
state: Florida
Study officials:
affiliation: University of Miami
name: Rodolfo Alejandro, MD
role: PRINCIPAL_INVESTIGATOR
References: