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

Protocol to screen potential subjects for islet transplantation

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus

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

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Diabetes Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects with type 1 DM

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
eligibility for islet transplantation	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.	Baseline

Collaborators and Investigators

• Sponsor: Rodolfo Alejandro

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): November 6, 2018
• Study Completion (Actual): November 6, 2018

Study Registration Dates

• First Submitted: November 25, 2013
• First Submitted That Met QC Criteria: December 3, 2013
• First Posted (Estimate): December 9, 2013

Study Record Updates

• Last Update Posted (Actual): December 11, 2018
• Last Update Submitted That Met QC Criteria: December 10, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 20053135

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED