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Summary

for people ages 12–21 (full criteria)
study started
estimated completion:

Description

Summary

Randomized, controlled, double blinded, multicenter, phase I/II clinical trial to evaluate the safety of low-dose IL-2 and to test whether low-dose IL-2 can prevent further loss of beta-cell function in patients with established T1D, or even potentially improve ß-cell function in such individuals, when IL-2 is given for one year (primary outcome). Equally important, the study will carefully examine various effects of low-dose IL-2 on the immune system in patients with T1D, including effects on Treg and other cell subsets, and disease-specific autoimmune responses.

Official Title

A Randomized, Double Blind, Phase I/II Trial of Low-Dose Interlekin-2 Immunotherapy in Established Type 1 Diabetes

Details

This will be a randomized, controlled, double blinded, multicenter, phase I/II clinical trial to evaluate the safety of low-dose IL-2 and to test whether low-dose IL-2 can prevent further loss of beta-cell function in patients with established T1D, or even potentially improve ß-cell function in such individuals, when IL-2 is given for one year (primary outcome). Equally important, the study will carefully examine various effects of low-dose IL-2 on the immune system in patients with T1D, including effects on Treg and other cell subsets, and disease-specific autoimmune responses.

Patients to be included in this study are those diagnosed with T1D who would have had T1D from 4 months to 1 year at the time of randomization, who have current or past demonstration of autoimmunity (using autoantibodies), and maintain preserved beta-cell function, defined as a MMTT stimulated C-peptide >0.2 nmol/L. This population is chosen because it will extend the scope of therapy beyond the immediate time following diagnosis, when most previous studies of immunotherapy in T1D have been conducted, and impact the field if a therapeutic benefit can be shown when the disease is more established.

Potential participants will have a screening visit to review overall health, measure diabetes T1D-associated autoantibodies and perform a MMTT, which will also serve as the baseline MMTT. Eligible subjects will be invited to participate in the intervention trial and randomized to treatment with Proleukin® or placebo. Fifty-four patients will be enrolled, aged 12-21 years, both genders, and randomized to treatment or placebo in a 2:1 ratio. Participation for each subject will last approximately 2 years. The 18 patients randomized to the control arm will receive placebo for two years. At the end of the first year, the 36 patients randomized to the treatment arm will be randomized 1:1 to continued treatment or placebo. Thus, among the 36 patients who received treatment during the first year, 18 patients will continue therapy and 18 patients will switch to placebo until the end of the study. This study design allows examining safety and efficacy at one year (primary outcome), and further evaluates these parameters after the therapy has stopped or it is continued up to the end of 2 years (secondary outcome).

The clinical investigator(s) will evaluate beta-cell function by examining C-peptide response during a MMTT, and using glucose and C-peptide data obtained during the MMTTs investigator(s) will determine beta-cell sensitivity to glucose, insulin sensitivity, and insulin secretion using the Mari model (99). It is documented that ß-cells in T1D are "blind" to glucose, by showing reduced ß-cell sensitivity to glucose using the Mari model in relatives at risk of T1D (100). The extent, to which this may account for reduced ß-cell function, and whether this is to any degree reversible, is unknown. Thus, clinical investigator(s) will characterize ß-cell function in response to low-dose IL-2 by measuring insulin secretion during a 4-hour MMTT, and using the Mari model to calculate ß-cell sensitivity to glucose and insulin sensitivity/resistance.

In other trials with low-dose IL-2, risks have been minimal compared to the well-known side effects of high dose IL-2. Risks of low-dose IL-2 include some potential side effects, such as pain or skin reactions at the injection site, with potential discomfort, redness, swelling, or even a scab at the injection site; flu-like symptoms, nausea, and diarrhea. Unexpected risks are always possible.

Keywords

Diabetes Mellitus, Type 1 Diabetes Diabetes, Autoimmune Diabetes Mellitus Aldesleukin

Eligibility

You can join if…

Open to people ages 12–21

  • 12-21 years of age
  • T1D, demonstrated by at least one islet autoantibody
  • T1D duration 4-12 months at the time of the first dose
  • Peak stimulated C-peptide >0.2 nmol/L during a 4-hour MMTT

You CAN'T join if...

  • Treatment with oral anti-diabetic agents
  • Illnesses that would preclude use of low-dose IL-2

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
Jay S. Skyler
ID
NCT03243058
Phase
Phase 1/2
Study Type
Interventional
Last Updated
August 3, 2017
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