Islet Isolation Using MnTE-2-PyP (BMX-010) - Pilot Study

This is an interventional treatment trial for Type 1 Diabetes focused on measuring Type 1 Diabetes, Islet Transplant Read More

Inclusion Criteria:

To be eligible the participant must have had type 1 diabetes mellitus (T1DM) for more than 5 years, complicated by at least 1 of the following situations that persist despite intensive insulin management efforts:

• a. Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at plasma glucose levels < 3.0 mmol/L, indicated by, 1 or more episodes of severe hypoglycemia requiring third party assistance within 12 months, a Clarke score ≥4, HYPO score ≥1,000, lability index (LI) ≥400 or combined HYPO/LI >400/>300.
• b. Metabolic instability, characterized by erratic blood glucose levels that interfere with daily activities and or 1 or more hospital visits for diabetic ketoacidosis over the last 12 months.
• Participants must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.

Exclusion Criteria:

• 1. History of enrollment in any other islet transplant trials (at the discretion of the investigator).
• 2. Severe co-existing cardiac disease, characterized by any one of these conditions: (a) recent (within the past 6months) myocardial infarction; (b) left ventricular ejection fraction <30%; or (c) evidence of ischemia on functional cardiac exam.
• 3. Active alcohol or substance abuse, to include cigarette smoking (must be abstinent for 6 months prior to listing for transplant).
• 4. 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).
• 5. History of non-adherence to prescribed regimens.
• 6. Active infection including Hepatitis C, Hepatitis B, HIV, or TB (subjects with a positive PPD performed within one year of enrollment, and no history of adequate chemoprophylaxis).
• 7. Any history of, or current malignancies except squamous or basal skin cancer.
• 8. BMI > 35 kg/m2 at screening visit.
• 9. Age less than 18 or greater than 68 years.
• 10. Measured glomerular filtration rate (GFR) <60 mL/min/1.73 m2.
• 11. Presence or history of macroalbuminuria (>300 mg/g creatinine).
• 12. Clinical suspicion of nephritic (hematuria, active urinary sediment) or rapidly progressing renal impairment (e.g. Increase in serum creatinine of 25% within the last 3-6 months).
• 13. Baseline Hb < 105g/L (<10.5 g/dL) in women, or < 120 g/L (<12 g/dL) in men.
• 14. Baseline screening liver function tests outside of normal range, with the exception of uncomplicated Gilbert's Syndrome. An initial LFT panel with any values >1.5 times the upper limit of normal (ULN) will exclude a patient without a re-test; a re-test for any values between ULN and 1.5 times ULN should be made, and if the values remain elevated above normal limits, the patient will be excluded.
• 15. Untreated proliferative retinopathy.
• 16. Positive pregnancy test, intent for future pregnancy or male subjects' intent to procreate, failure to follow effective contraceptive measures, or presently breast-feeding.
• 17. Evidence of significant sensitization on PRA (at the discretion of the investigator).
• 18. Insulin requirement >1.0 U/kg/day
• 19. HbA1C >12%.
• 20. Uncontrolled hyperlipidemia [fasting LDL cholesterol > 3.4 mmol/L (133 mg/dL), treated or untreated; and/or fasting triglycerides > 2.3 mmol/L (90 mg/dL)].
• 21. Under treatment for a medical condition requiring chronic use of steroids.
• 22. Use of coumadin or other anticoagulant therapy (except aspirin) or subject with PT/INR > 1.5.
• 23. Untreated Celiac disease.
• 24. Patients with Graves disease will be excluded unless previously adequately treated with radioiodine ablative therapy.