Type 1 diabetes (T1D) results from the killing of insulin-producing pancreatic beta cells by cells of the immune system. The study aims to slow the progressive, immune-mediated loss of insulin-producing beta cells that occurs after clinical presentation. The investigators have identified a pathway that is important for immune cells to kill beta cells, and a drug that will block this pathway and prevent beta cell death. This drug, baricitinib, is already in clinical use for rheumatoid arthritis, and is currently in clinical trials for other diseases, including childhood autoimmune diseases. It is hypothesized that baricitinib treatment for 48 weeks will preserve beta cell function in children and young adults with recently-diagnosed T1D. The trial aims to recruit 83 participants aged 10-30 years who have been recently diagnosed with T1D. Two thirds of the participants will be randomly assigned to receive baricitinib, one third will receive placebo. The trial will test if baricitinib can slow the progressive loss of insulin-producing beta cells in these patients. The primary objective is to determine if baricitinib can reduce the loss of meal-stimulated plasma C-peptide, a measure of beta-cell function. Maintaining endogenous insulin in recent-onset T1D improves glucose control and may lead to long-term improvements in glucose and lower rates of serious diabetes complications and death.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
91
Participants will take one tablet of study drug per day for 48 weeks, and will be followed up for 48 weeks after study drug treatment has finished. Two-thirds of participants will receive Baricitinib.
Participants will take one tablet of study drug per day for 48 weeks, and will be followed up for 48 weeks after study drug treatment has finished. One-third of participants will receive Placebo.
Women's and Children's Hospital Adelaide
North Adelaide, South Australia, Australia
St Vincent's Hospital Melbourne
Fitzroy, Victoria, Australia
Royal Melbourne Hospital
Parkville, Victoria, Australia
Royal Children's Hospital Melbourne
Parkville, Victoria, Australia
The primary endpoint of the study is the change from baseline of plasma C-peptide area under the curve (AUC) over 2 hours following a mixed meal.
Time frame: Measured at 48 weeks post commencement of intervention.
Change from baseline in plasma C-peptide AUC over 2 hours following a mixed meal.
Time frame: Measured at weeks 12, 24, 72 and 96 post commencement of intervention.
Change from baseline in mean daily insulin use over 7 consecutive days.
Time frame: Measured during the 2 weeks prior to the assessment at weeks 12, 24, 48, 72 and 96 post commencement of intervention.
Change from baseline in glycosylated haemoglobin (HbA1c) levels.
Time frame: Measured at weeks 12, 24, 48, 72 and 96 post commencement of intervention.
Number of participants with responder status. Responder status is defined as glycosylated haemoglobin (HbA1c) less than or equal to 6.5 percent and mean daily insulin use less than 0.5 international units per kilogram per day (IU/kg/day).
Time frame: Measured at weeks 12, 24, 48, 72 and 96 post commencement of intervention.
Change in estimated C-peptide (CPEST) from baseline. CPEST is calculated based on six variable routine measures: disease duration, BMI, insulin dose, HbA1c, fasting plasma C-peptide and fasting plasma glucose.
Time frame: Measured at weeks 12, 24, 48, 72 and 96 post commencement of intervention.
Continuous glucose monitoring (CGM).
Time frame: Measured at baseline, 12, 24, 48 and 96 weeks post commencement of intervention.
The composite outcome assessing both the frequency, and when relevant, the severity of all adverse events.
Time frame: Adverse events will be monitored throughout the entire study duration at weeks 0, 2, 4, 8, 12, 16, 20, 24, 36, 48, 72 and 96.
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