|First Received Date ICMJE||June 5, 2017|
|Last Updated Date||June 7, 2017|
|Start Date||July 1, 2017|
|Estimated Primary Completion Date||June 30, 2021|
|Current Primary Outcome Measures ICMJE
(submitted: N/A )
Change of 2-hour mixed meal stimulated C-peptide AUC
Time frame: Baseline, Month 3, 6, 9, 12, 18 and 24
Designated as safety issue:
This AUC will be normalized by dividing it by 120 minutes (the number of minutes over which it is determined), and will be adjusted by inclusion of baseline C-peptide AUC as a covariate in the analysis.
|Original Primary Outcome Measures ICMJE||Same as current|
|Current Secondary Outcome Measures ICMJE
Time frame: Month 3, 6, 9, 12, 18 and 24
Designated as safety issue:
A subject is considered a responder if at the given time point, the subject has: a) HbA1c ?6.5% and b) mean daily insulin use < 0.5 IU/kg/day over 7 consecutive days during the 2 weeks preceding the visit.
|Original Secondary Outcome Measures||N/A|
|Current Other Outcome Measures||N/A|
|Original Other Outcome Measures||N/A|
|Brief Title||Stem Cell Mobilization (Plerixafor) and Immunologic Reset in Type 1 Diabetes (T1DM)|
|Official Title||Autologous Hematopoietic Stem Cell Mobilization (Plerixafor) and Immunologic Reset in New Onset Type 1 Diabetes Mellitus|
Type 1 diabetes is an autoimmune disease characterized by destruction of pancreatic
beta-cells, resulting in absolute deficiency of insulin. Presently there is no known cure.
Our proposed interventional trial is based on \'immunological reset\' approach: T-depletion
therapy and anti-inflammatory treatment will restore self-tolerance in T1DM; Autologous,
peripheral-blood mobilized hematopoietic CD34+-enriched stem cells and a long-acting GLP-1
analogue will promote pancreatic islet regeneration and repair.
The short-term goals of this protocol is to demonstrate that subjects with new-onset T1DM
undergoing autologous hematopoietic stem cell mobilization and immunologic reset will have
greater preservation of endogenous insulin secretion compared to controls, and foremost that
this nonmyeloablative treatment is safe, without the need for chronic immune suppression.
|Study Phase||Phase 1/Phase 2|
|Condition||Diabetes Mellitus, Type 1|
|Study Arm (s)||
Experimental - Treated arm
For participants assigned to the treated arm, they will follow study regime illustrated in the figure below: Intervention treatment will last from Day 0 up to Month 24. Day 0: Subjects will receive alemtuzumab (30mg iv single dose); anakinra (100 mg sc.); etanercept (50 mg sc.) and liraglutide (0.6 mg sc.). Day 1: Subjects will receive plerixafor (0.24 mg/kg/day) sc. to mobilize CD34+ stem cells to peripheral blood. Day 1: Continuing with anakinra 100mg sc. daily for 12 month; etanercept 50mg sc. twice weekly for first 3 months, and 50mg sc. weekly for another 9 months; liraglutide 0.6 mg sc. daily for 7 days, then 1.2 mg sc. daily (or up to 1.8mg daily) as tolerated for 24 months.
Other - Control arm
For participant assigned to the control arm, they will be monitored and tested for the first 12 months, and receive intervention treatment from Month 12 up to Month 24. Month 12: Subjects will receive alemtuzumab (30mg iv single dose); anakinra (100 mg sc.); etanercept (50 mg sc.) and liraglutide (0.6 mg sc.). Month 12 + 1 day: Subjects will receive plerixafor (0.24 mg/kg/day) sc.. Month 12 + 1 day: Continuing with anakinra 100mg sc. daily for 12 month; etanercept 50mg sc. twice weekly for first 3 months, and 50mg sc. weekly for another 9 months; liraglutide 0.6 mg sc. daily for 7 days, then 1.2 mg sc. daily (or up to 1.8mg daily) as tolerated for 12 months.
|Other Study ID Numbers||Pro00053082|
|Has Data Monitoring Committee||Yes|
|Responsible Party||University of Alberta|
|Study Sponsor||University of Alberta|
Alberta Innovates Health Solutions
|Information Provided By||University of Alberta|
|Verification Date||June 2017|
Andrew Malcolm, PhDSend Email 780-407-6952
Type 1 diabetes is an autoimmune disease characterized by destruction of pancreatic beta-cells, resulting in absolute deficiency of insulin. Presently there is no known cure. Our proposed interventional trial is based on \'immunological reset\' approach: T-depletion therapy and anti-inflammatory treatment will restore self-tolerance in T1DM; Autologous, peripheral-blood mobilized hematopoietic CD34+-enriched stem cells and a long-acting GLP-1 analogue will promote pancreatic islet regeneration and repair. The short-term goals of this protocol is to demonstrate that subjects with new-onset T1DM undergoing autologous hematopoietic stem cell mobilization and immunologic reset will have greater preservation of endogenous insulin secretion compared to controls, and foremost that this nonmyeloablative treatment is safe, without the need for chronic immune suppression.
|Diabetes Mellitus, Type 1||Phase 1/Phase 2|
- Study Type:
- Study Design:
- Official Title:
- Autologous Hematopoietic Stem Cell Mobilization (Plerixafor) and Immunologic Reset in New Onset Type 1 Diabetes Mellitus
- Estimated Enrollment:
- Listed Countries:
- Removed Countries:
- Minimum Age Eligible for Study:
- 18 Years
- Maximum Age Eligible for Study:
- 45 Years
- Gender Eligible for Study:
- Accepts Healthy Volunteers:
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. Exclusion Criteria
Duration of T1DM longer than 180 days
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.
Active alcohol or substance abuse, including cigarette smoking (must be abstinent for 6 months prior to study enrolment).
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.
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).
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).
BMI > 35 kg/m2 at screening visit.
Age less than 18 or greater than 45 years.
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.
Untreated proliferative retinopathy.
Positive pregnancy test, intent for future pregnancy or male subjects\' intent to procreate, failure to follow effective contraceptive measures, or presently breast feeding.
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.
Insulin requirement >1.0 U/kg/day
HbA1C >12% at screening.
Uncontrolled hyperlipidemia [fasting LDL cholesterol > 3.4 mmol/L, treated or untreated; and/or fasting triglycerides > 2.3 mmol/L]
Under treatment for a medical condition requiring chronic use of steroids.
Use of coumadin or other anticoagulant therapy (except aspirin) or subject with PT INR > 1.5.
Untreated Celiac disease.
Patients with Graves disease unless previously adequately treated with radioiodine ablative therapy.
Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
Hypersensitive to E. coli derived protein.
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.
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|1.||University of Alberta||University of Alberta,Edmonton,Alberta,Canada,T6G 2C8|
|Not yet recruiting Not Enrolling|
No Study Results Posted on ClinicalTrials.gov for this Study
About Study Results Reporting on ClinicalTrials.gov
|Estimated Study Completion Date:||December 31, 2021|
|Estimated Primary Completion Date:||June 30, 2021|
|Results First Received: June 5, 2017|
|Conditions:||Diabetes Mellitus, Type 1|