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

Sponsor
University of Alberta
Study ID
NCT03182426
Phase
PHASE1/PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 45 Years
Healthy Volunteers
Not accepted

Interventions

  • Plerixafor — DRUG
    Systemic CD34+ stem cell mobilization for beta-cell repair
  • Alemtuzumab — DRUG
    T-cell depletion
  • Anakinra — DRUG
    Anti-inflammatory
  • Etanercept — DRUG
    Anti-inflammatory
  • Liraglutide — DRUG
    Beta-cell regeneration

Study Details

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.

Key Dates

Start date
Aug 15, 2017
Status verified
Jul 2024
Primary completion
Jul 15, 2024
Completion
Jul 15, 2024

Study Design

Enrollment
22 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Treated arm
    For participants assigned to the treated arm, they will follow study regime 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.
  • Experimental: 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.

Primary Outcome Measure

Change of 2-hour mixed meal stimulated C-peptide AUC [ Time Frame: Baseline, Month 3, 6, 9, 12, 18 and 24 ]

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