Stem Cell Mobilization (Plerixafor) and Immunologic Reset in Type 1 Diabetes (T1DM)

Prior treatment

• Active alcohol or substance abuse, including cigarette smoking (must be abstinent for 6 months prior to study enrolment).
• Significant systemic infection during the 3 weeks before the start of study intervention (e.g., infection requiring hospitalization, major surgery, or IV antibiotics to resolve; other infections, e.g., bronchitis, sinusitis, localized cellulitis, candidiasis, or urinary tract infections, must be assessed on a case-by-case basis by the investigator regarding whether they are serious enough to warrant exclusion).
• EBV viral load of \> 10,000 copies per 106 peripheral blood mononuclear cells (PBMCs) as determined by quantitative polymerase chain reaction (qPCR). If there is any clinical suspicion that a subject who is EBV seronegative and with EBV PCR \< 10,000 copies per 106 PBMCs has symptoms consistent with infectious mononucleosis prior to administration of study treatment, then a monospot test result must be negative before the subject can be enrolled.
• Positive result on the Rapid Plasma Reagin (RPR) test for syphilis; except if result of RPR test is positive, a negative confirmatory test (for example, fluorescent treponemal antibody absorbed \[FTA-ABS\] test).
• History of using any investigational drug within the 3 months before enrollment of this study.
• History of using any potent immunosuppressive agent (e.g., systemic high-dose corticosteroids on a chronic basis, methotrexate, cyclosporine, or anti-TNF agents) within the 30 days before the study treatment.
• History of receiving any live vaccine within the 30 days before the study treatment.
• Any major surgical procedure within 30 days before the study treatment.
• Patients with Graves disease unless previously adequately treated with radioiodine ablative therapy.

Other illness

• Psychiatric disorder making the subject not a suitable candidate for this study (e.g., schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medication).
• History of non-adherence to prescribed regimens.
• Hypersensitivity to any of the required study medications.
• Active infection including Hepatitis C, Hepatitis B, HIV, tuberculosis (subjects with a positive PPD performed within one year of enrollment, and no history of adequate chemoprophylaxis).
• Any history of, current malignancies, other than non-melanoma skin cancer (To be included to the study, subject must have had fewer than 5 occurrences of non-melanoma skin cancer, and the last occurrence must not be within 3 months of study entry).
• Positive pregnancy test, intent for future pregnancy or male subjects' intent to procreate, failure to follow effective contraceptive measures, or presently breast feeding.
• Under treatment for a medical condition requiring chronic use of steroids.
• Untreated Celiac disease.
• Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.

Lab values

• Severe co-existing cardiac disease, characterized by any one of these conditions: (a) recent myocardial infarction (within past 6 months); (b) left ventricular ejection fraction \<30%; or (c) evidence of ischemia on functional cardiac exam.
• Measured glomerular filtration rate (GFR) \< 60 m/min/1.73m2
• Presence or history of macroalbuminuria (\>300 mg/g creatinine)
• 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).
• Baseline Hb \< 105g/L in women, or \< 120 g/L in men.
• 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.
• HbA1C \>12% at screening.
• Uncontrolled hyperlipidemia \[fasting LDL cholesterol \> 3.4 mmol/L, treated or untreated; and/or fasting triglycerides \> 2.3 mmol/L\]
• Use of coumadin or other anticoagulant therapy (except aspirin) or subject with PT INR \> 1.5.
• Clinically significant abnormal lab values during the screening period, other than those due to T1DM. Permitted ranges for selected lab values are shown in the Table below. A clinically significant abnormal value will not result in exclusion if, upon re-test, the abnormality is resolved or becomes clinically insignificant.

Age

• Age less than 18 or greater than 45 years.

Other

• Duration of T1DM longer than 180 days
• BMI \> 35 kg/m2 at screening visit.
• Untreated proliferative retinopathy.
• Insulin requirement \>1.0 U/kg/day
• Hypersensitive to E. coli derived protein.

• Patient is aged 18-45
• To be eligible participants must have:
• A clinical diagnosis of type 1 diabetes using the diagnostic criteria of the CDA
• Residual β-cell function, defined by a stimulated C-peptide \> 0.6 but ≤10.5 ng/mL on MMTT;
• One or more positive autoantibodies: (GAD, ICA512, IA2A, ZnT8, mIAA) to confirm T1DM;
• No underlying condition that would preclude enrolment at PI's discretion.
  • Participants must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent, with additional parental consent where required.