| Outcome Measures: |
Primary: Proportion of patients with HbA1c <7% and daily insulin requirement <0.50 IU/Kg/day, The sample size of the study is calculated on the "proportion of patients with a HbA1c \< 7% and daily insulin requirement \<0.50 IU/Kg/day", a post-hoc composite endpoint derived from data of the phase 2 trial (MEX0114), considering a larger effect size expected from the longer treatment length (one year versus 3 months). The time frame for the primary endpoint has been set at Month 12 (Week 52) in order to evaluate the potential of ladarixin effects on a long-term projection., Month 12 | Secondary: Proportion of patients with HbA1c < 7% and daily insulin requirement <0.50 IU/Kg/day, The sample size of the study is calculated on the "proportion of patients with a HbA1c \< 7% and daily insulin requirement \<0.50 IU/Kg/day", a post-hoc composite endpoint derived from data of the phase 2 trial (MEX0114), considering a larger effect size expected from the longer treatment length (one year versus 3 months). Follow-up is extended up to 18 months to evaluate the potential persistency of any glycemic benefit., Months 6 and 18|Proportion of patients with a reduction in HbA1c% > 0.5% from baseline and daily insulin requirement <0.50 IU/Kg, Proportion of patients with a reduction in HbA1c% \> 0.5% from baseline and daily insulin requirement \<0.50 IU/Kg/day was calculated, Months 6, 12 and 18|2-hour AUC of C-peptide response to the MMTT, C-peptide level is a widely used measure of pancreatic beta-cell function. The MMTT is one of the methods for its estimation. The MMTT was performed after an overnight fast, at baseline (within 1 week prior to randomization), and at each follow-up visit on weeks 13±1, 26±2, and 52±2. Prior to the test, patients withheld long-acting insulin on the morning of the test. Rapid-acting and short-acting insulin were allowed up to 6hrs and 2 hrs, respectively, before the test. The test was rescheduled if the patient had a capillary glucose value of \>200mg/dL or \<70mg/dL. After 2 pre-meal basal samples had been drawn between -20 to 0 min (basal 1 and basal 2), patients were given 6mL/kg of a high protein nutritional drink up to a maximum of 360mL, to be drunk within 5 min. Post-meal samples were drawn at 15, 30, 60, 90, 120 min after the meal at Months 6, 12 and 18., Months 6, 12 and 18|Time in range (TIR) by Continuous Glucose Monitoring (CGM), Continuous glucose monitors (CGM) continually monitors glucose plasma levels through an external device that's attached to the body, and gives real-time updates.Time in range is the amount of time the patient spends in the target blood sugar (blood glucose) range-between 70 and 180 mg/dL for most people. The time in range method works with the individual CGM's data by looking at the amount of time blood sugar has been in target range and the times it has been high (hyperglycemia) or low (hypoglycemia). This data is helpful in finding out which types of foods and what activity level causes patient's blood sugar to rise and fall., Months 6, 12 and 18|HbA1c levels, HbA1c measurement can be used as a diagnostic test for diabetes providing that stringent quality assurance tests are in place and assays are standardised to criteria aligned to the international reference values, and there are no conditions present which preclude its accurate measurement. An HbA1c of 6.5% is recommended as the cut point for diagnosing diabetes. A value of less than 6.5% does not exclude diabetes diagnosed using glucose tests., Months 6, 12 and 18|Proportion of patients with HbA1c < 7% who did not experience severe hypoglycemic events during treatment, For the purpose of this study, a severe hypoglycaemic event is defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood glucose level \<54mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration., Months 6, 12 and 18|Additional Glucose Variability Indices derived from CGM: PPG, PPG=2-hour postprandial glucose. All these glycemic variability indices refer to the intra-day or inter-day values and differences derived from the glucose values (these latter expressed in mg/dL) collected index by index using continuous glucose monitoring (CGM) System, Months 6, 12 and 18|Additional Glucose Variability Indices derived from CGM: MAGE, MAGE=Mean Amplitude Glycemic Excursions. All these glycemic variability indices refer to the intra-day or inter-day values and differences derived from the glucose values (these latter expressed in mg/dL) collected index by index using continuous glucose monitoring (CGM) System., Months 6, 12 and 18|Additional Glucose Variability Indices derived from CGM: CONGA-n, CONGA-n=continuous overall net glycemic action. All these glycemic variability indices refer to the intra-day or inter-day values and differences derived from the glucose values (these latter expressed in mg/dL) collected index by index using continuous glucose monitoring (CGM) System., Months 6, 12 and 18|Additional Glucose Variability Indices derived from CGM: MODD, MODD=Mean Of the Daily Differences. All these glycemic variability indices refer to the intra-day or inter-day values and differences derived from the glucose values (these latter expressed in mg/dL) collected index by index using continuous glucose monitoring (CGM) System., Months 6, 12 and 18|Additional Glucose Variability Indices derived from CGM: mean daily blood glucose, All these glycemic variability indices refer to the intra-day or inter-day values and differences derived from the glucose values (these latter expressed in mg/dL) collected index by index using continuous glucose monitoring (CGM) System., Months 6, 12 and 18|Additional Glucose Variability Indices derived from CGM: Standard Deviation (SD), All these glycemic variability indices refer to the intra-day or inter-day values and differences derived from the glucose values (these latter expressed in mg/dL) collected index by index using continuous glucose monitoring (CGM) System., Months 6, 12 and 18|Number of self-reported episodes of severe hypoglycemia, For the purpose of this study, a severe hypoglycaemic event is defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood glucose level \<54mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration., Months 6, 12 and 18|Average (previous 3 days) daily insulin requirements (IU/kg/day), For the purpose of this study, daily insulin is averaged over the previous 3 days.Insulin requirement (IU/kg/day averaged over the previous 3 days) was to be recorded to Months 6, 12 and 18. Patients were admitted to intensive diabetes management, according to current ADA recommendation \[2014\]. Patients were instructed to self-monitor their glucose values at least 4 times a day and to report (glucose meter/log) outcome to the diabetes management team. Insulin intake was adjusted to target HbA1c levels of less than 7% and self-monitored (fingerstick): * pre-prandial blood glucose of 70-130 mg/dL * post-prandial blood glucose \< 180 mg/dL * bed-time blood glucose of 110-150 mg/dL, Months 6, 12 and 18|Estimated Glucose Disposal Rate (eGDR), Estimated Glucose Disposal Rate (eGDR) is a marker for the Assessment of Insulin Resistance and a validated clinical tool for estimating insulin sensitivity in type 1 diabetes., Months 6, 12 and 18|Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs), An AE is any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the trial intervention. A serious adverse event is an adverse event that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a birth defect., Throughout the study up to 18 months
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| Locations: |
University of Colorado School of Medicine - Barbara Davis Center for Childhood Diabetes (BDC) - Specialty Clinic, Aurora, Colorado, 80045, United States|Atlanta Diabetes Associates (ADA), Atlanta, Georgia, 30318, United States|Universitair Ziekenhuis Brussel (UZB), Jette, Belgium|National Center for Diabetes Research LTD, Tbilisi, 48159, Georgia|National Institute of Endocrinology LTD, Tbilisi, 48159, Georgia|Universitaetsklinikum Gessen und Marburg GmbH - Medizinische Klinik und Poliklinik III, Glessen, 35392, Germany|Die Praxis am Ludwigsplatz, Ludwigshafen, 67059, Germany|Institut fuer Diabetes forschung in Muenster (IDFM), Muenster, 48145, Germany|Azienda Ospedaliero-Universitaria Conzorziale Policlinico di Bari, Bari, 70124, Italy|Università degli Studi Magna Graecia di Catanzaro, Azienda Ospedaliero-Universitaria Mater Domini, Catanzaro, 88100, Italy|Universitá degli Studi di Milano - Ospedale Luigi Sacco, Milan, 20157, Italy|Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone", Palermo, 90127, Italy|Università Campus Bio-Medico di Roma (UCBM), Roma, 00128, Italy|"Sapienza" Università di Roma- Azienda Ospedaliero Universitaria Policlinico Umberto I, Rome, 00161, Italy|Clinical Center of Serbia, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Belgrade, 11000, Serbia|Clinical center Kragujevac, Clinic for internal diseases, Center for endocrinology, diabetes and metabolic diseases, Kragujevac, 34000, Serbia
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