This phase I trial investigates the side effects of PIpepTolDC vaccine in treating patients with type 1 diabetes who use insulin and don't have any other diabetes-related health complications. Type 1 diabetes is an autoimmune disease. This means that the immune system, which usually protects against foreign invaders like bacteria and viruses, attacks the body's insulin-producing betacells in the pancreas (autoimmune response). Overtime, the beta cells are destroyed by the immune system. To stay alive, people with type 1 diabetes must use insulin. PIpepTolDC vaccine is a type of immunotherapy (a treatment that uses a person's own immune system) that works like an allergy shot. The vaccine is made using one's own immune cells (dendritic cells) and a beta cell protein. The vaccine may teach the immune system to stop attacking the beta cells, which may help the beta cells recover and make enough insulin to control blood sugar levels. The vaccine may also help reduce future type 1 diabetes related complications.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
PIpepTolDCs
City of Hope Medical Center
Duarte, California, United States
Incidence of adverse events
Toxicity and adverse events (except hypoglycemia and diabetic ketoacidosis \[DKA\]) will be recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Hypoglycemia events and DKA will be defined per American Diabetes Association (ADA) grading systems.Observed toxicities will be summarized by type, severity (by CTCAE v 5.0 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution.
Time frame: Up to 2 years
Apheresis duration
Measured in hours.
Time frame: up to 2 years
Number of CD14+ monocytes
Number of CD14+ monocytes collected during apheresis
Time frame: up to 2 years
TolDC recovery after culture
Number of TolDC generated from CD14+ monocytes
Time frame: up to 2 years
Number of successful manufactured products
Number of manufactured products that meet the required cell dose/day, sterility (e.g. endotoxin and gram staining), and viability compared to the total number of products manufactured.
Time frame: Up to 2 years
Change in stimulated C-peptide area under the curve
Assessed via 2-hr mixed meal tolerance test (MMTT). C-peptide preservation is defined as the maintenance of baseline C-peptide levels.
Time frame: Baseline up to 2 years of follow up
Change in interferon (IFN)-gamma and IL-10 producing CD4+ T cells
Will be assessed in response to pro-insulin peptide C19-A3, and assessed via cytokine enzyme-linked immunosorbent spot assay.
Time frame: Baseline up to 2 years of follow up
Change in T cell responsiveness
Will assess for changes in T cell responsiveness to pro-insulin peptide C19-A3 compared to other antigens. Assessed via Lymphocyte Simulation Test.
Time frame: Baseline up to 2 years of follow up
Change in the number of CD8+ autoreactive T cells
Assessed via quantum dot (Q-DOT) nanotechnology assay.
Time frame: Baseline up to 2 years of follow up
Change in immune phenotype
Will analyze for changes in immune cell populations via flow cytometry
Time frame: Baseline up to 2 years of follow up
Change in islet autoantibodies
Will analyze for changes in IAA, GAA, IA-2A, ZnT8A via enzyme-linked immunosorbent assay.
Time frame: Baseline up to 2 years of follow up
Change in glycosylated hemoglobin A1c (HbA1c) levels
HbA1c levels will be assessed via blood test
Time frame: Baseline up to 2 years of follow up
Change in exogenous insulin use (units/kg)
Insulin usage will be recorded daily from the insulin pump and/or participant insulin use logs. The mean daily insulin usage over the 10 consecutive days (IU units/kg body weight/day) preceding the clinic visit will be calculated for each participant.
Time frame: Baseline up to 2 years of follow up
Change in blood glucose levels
Will include clinically important/severe hypoglycemia, hyperglycemia and DKA events as assessed by ADA grading systems. Levels of glucose will be assessed from bloods samples taken during the MMTT and from insulin pump/participant insulin logs
Time frame: Baseline up to 2 years of follow up
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