The goal of this clinical trial is to evaluate of the effect of phenofibrate on the functions of beta cells in children with new diagnosis of type 1 diabetes. The main question it aims to answer is: whether phenofibrate may prolong residual beta-cell function therefore own insulin secretion. Participants will be asked to take a phenofibrate or identically appearing placebo (a neutral substance), orally, once daily, for 12 months with no knowledge what is administred to them. They will be invited for follow-up visits including blood tests every 3 months. Researchers will be monitoring the two groups for the safety of the phenofibrate, and at the trial end they compare the residual insulin secretion results in two groups.
Rationale: Preservation of residual pancreatic beta cell function in children with newly diagnosed T1D gives a chance for better diabetes control, reduction of chronic diabetes complications, and possibly temporary insulin withdrawal. Indication of a cheap drug for secondary prevention of T1D. Setting: Recruitment will be through the paediatric diabetes clinics at two participating centres in Warsaw, Poland (Department of Paediatrics, the Medical University of Warsaw and Department of Endocrinology and Diabetology, Children's Memorial Health Institute). The initiation of study treatment may be performed no later than 28 days after screening visit, and no later than in 8 weeks from diabetes diagnosis. PICO: Adolescent participants meeting inclusion criteria, newly diagnosed with type 1 diabetes will be randomly assigned to two groups, receiving either fenofibrate at a dose of 160 mg or placebo, and regularly assesed, every 3 months for the next year. Assuming increase by 50% of AUC of C-peptide in the test group compared to placebo, 88 subjects are needed to achieve power of 85%. If about 13% drop-out is assumed the total group size is 102 patients. Given randomization ratio 1:1, there is 51 patients in each group. Main study procedures: * Demographic and medical history. * Physical examination and vital signs: heart rate and blood pressure, respiration rate, body temperature. * Blood collection for laboratory analysis (hematology: morphology with automatic blood smear, biochemistry: ALT, AST, total bilirubin, albumin, amylase, lipase, total cholesterol, HDL, LDL, triglycerides, GGTP, HbA1c, TSH, FT4, Anti-Tg, Anti-TPO, CK, creatinine, urea, vitamin D, homocysteine, Anti-tTG IgA, IgA. * Urine pregnancy test (in girls with childbearing potential). * C-peptide and Glucose in MMTT stimulation assay. * Anti-insulin IAA antibodies, Antibodies to glutamic acid decarboxylase (GADA), Antibodies to tyrosine phosphatase (IA2A), Antibodies to the zinc transporter 8 (ZnT8). * IL1, IL2, IL10. * TNF alpha, IFN gamma. * Genetic study - WES genome sequencing, HLA DR3, DR4, DO8, DQ7. * FGM Libre Free Style Glucose Monitoring System. * Abdominal ultrasound. * Ultrasound of the thyroid gland. * Safety monitoring and AE collection. * IMP administration. Compliance will be assessed by collecting empty packages as well as by direct interview and participants receiving \<75% of the recommended doses will be considered as non-compliant.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
102
Administred orally, once daily, for 12 months.
Administred orally, once daily, for 12 months.
Clinical department of pediatric diabetology and paediatrics, DSK UCKWUM
Warsaw, Masovian Voivodeship, Poland
RECRUITINGDiabetology Department, Children's Memorial Health Institute
Warsaw, Masovian Voivodeship, Poland
RECRUITINGDifferences in AUC in C-peptide stimulation test
Assessment of pancreatic beta cell function by comparing the area under the curve (AUC) in the C-peptide stimulation test: Change in the mean insulin secretion measured on the basis of the C-peptide area under the curve in the stimulation test
Time frame: 12 months
Differences in C-peptide concentration in the stimulation test: change in the insulin secretion measured on the basis of the fasting C-peptide concentration
Fasting C-peptide concentration in the stimulation test
Time frame: 0, 6, 12 months
Differences in parameters of diabetes control
HbA1c
Time frame: 0,3,6,9,12 months
Daily insulin requirement
Daily insulin requirement/kg of body mass
Time frame: 0,3,6,9,12 months
Interleukins
IL1, IL2, IL10, TNF alpha, IFN gamma
Time frame: 0,6,12 months
Adverse Events occurence
Safety will be evaluated through assessment of AEs, vital signs, physical examinations, USG findings, and laboratory evaluations. Any clinically significant laboratory occurring after study drug initiation must be reported by the investigator as an AE and/or SAE, as appropriate, and must be followed by additional laboratory evaluations until they return to normal range, stabilize, or until the change is no longer clinically relevant. All safety analyses will be conducted using the Safety Analysis Set. Adverse event data will be presented and tabulated according to MedDRA classification.
Time frame: 0,3,6,9,12 months
Differences in C-peptide concentration in the stimulation test: change in the insulin secretion measured on the basis of the fasting C-peptide concentration
Maximum C-peptide concentration
Time frame: 0,6,12 months
Diabetes control and glucose fluctuations
Mean blood glucose with standard deviation
Time frame: 0,3,6,9,12 months
Differences in glucose fluctuations
Glucose variability index (CV%)
Time frame: 0,3,6,9,12 months
Parameter of glucose fluctuations
Time in range 70-180mg/dl
Time frame: 0,3,6,9,12 months
Difference in autoantibodies
Difference in anti-insulin IAA antibodies, antibodies against glutamic acid decarboxylase (GADA), antibodies to tyrosine phosphatase (IA2A), anti-zinc transporter antibodies 8 determination.
Time frame: 0,6,12 month
Genetical analysis
WES Whole Exome Sequencing and HLA
Time frame: 1 per study
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