| Eligibility |
Inclusion Criteria:
1. clinical diagnosis of autoimmune T1D as documented by positive T1D diabetes-related
autoantibodies [the presence at diagnosis of at least one or more of - Insulin
autoantibodies (IAA), Anti-GAD (GAD65), Anti-IA2 (IA2), Zinc Transporter 8 (ZnT8) must
be documented from medical records or new laboratory measurement (not including IAA)];
2. age 21-65 years at the time of consent;
3. T1D duration =>5 years;
4. current insulin standard of care (ISOC), either use of an insulin pump or a stable
dose level and dose frequency (i.e. established dose range that does not fluctuate
beyond 1SD of the median over a period of the last two months prior to enrollment),
multiple daily injections of insulin (at least 3 injections per day) for the last two
months prior to enrollment, with no plans to switch the modality of insulin
administration during the 4 months following screening (e.g., injection user switching
to a pump, pump user switching to injections);
5. HbA1c between 7.5%-10.0%, inclusive, as per results of screening laboratory
measurement;
6. evidence of IR based on a total daily insulin dose >0.8 U/kg/ day and/or a screening
estimated glucose disposal rate (eGDR) < 9 mg/kg/min 1-3 value strongly indicative of
IR, sex- and ageadjusted;
7. subject is overweight or obese with a BMI of between 25-40 kg/m2, inclusive;
8. ability to comply with all protocol procedures for the duration of the study,
including scheduled follow-up visits and examinations, and willing to be contacted by
clinical trial staff;
9. provision of written informed consent prior of any study-related procedure not part of
standard medical care.
Exclusion Criteria:
1. patients with known or suspected hypersensitivity to non-steroidal anti-inflammatory
drugs or any excipient of the investigational medicinal products (e.g. lactose and
croscarmellose) as well as patients with congenital lactase deficiency, galactosaemia
or glucose-galactose intolerance will have to be excluded;
2. use of non-insulin medications for adjunctive blood glucose control (e.g: antidiabetic
agents such as metformin, sulfonylureas, glinides, thiazolidinediones, exenatide,
liraglutide, DPP-IV inhibitors, SGLT-2 inhibitors or amylin);
3. use of medications for weight reduction (such as: Belviq (lorcaserin), Qsymia
(Phentermine + topiramate), Orlistat (xenical));
4. use of a medication such as stimulants, antidepressants and/or psychotropic agents
that could affect weight gain or glycemic control of T1D;
5. subject is on treatment with drugs metabolized by CYP2C9 with a narrow therapeutic
index [i.e., phenytoin, warfarin, and high dose of amitriptyline (>50 mg/day)];
6. any medications known to influence glucose tolerance (e.g. beta-blockers,
angiotensin-converting enzyme inhibitors, interferons, quinidine antimalarial drugs,
lithium, niacin, etc.);
7. evidence of cardiac QTcF > 470 msec and/or any history of significant cardiovascular
disease/abnormality;
8. any condition, including unstable dietary approach and disordered eating behaviour
patterns, that in the judgment of the investigator will adversely affect patient's
safety or the completion of the protocol or otherwise confound study outcome;
9. pregnancy (females) based on serum test (quantitative beta hCG) at screening;
unwillingness to use effective contraceptive measures up to 2 months following trial
discharge (females and males);effective contraceptive measures include a hormonal
birth control (e.g. oral pills, long term injections, vaginal ring, patch); the
intrauterine device (IUD); a double barrier method (e.g. condom or diaphragm plus
spermicide foam).
10. clinical diagnosis of celiac disease that is in poor control as defined by most recent
tissue transglutaminase (tTG) that is in the abnormal range;
11. history of =1 Diabetic Ketoacidosis (DKA) events in the past 6 months;
12. history of =1 severe hypoglycemic events (cognitive impairment that required
assistance to treat) in the past 6 months;
13. hypoalbuminemia defined as serum albumin < 3 g/dL ;
14. hepatic dysfunction defined by increased ALT/AST > 3 x upper limit of normal (ULN) and
increased total bilirubin > 3 mg/dL [>51.3 µmol/L];
15. moderate to severe renal impairment calculated by estimated Glomerular Filtration Rate
(eGFR) <60 mL/min/1.73 m2 as determined using Chronic Kidney Disease Epidemiology
Collaboration (CKDEPI) creatinine equation;
16. poor accessibility to veins for blood collection;
17. past (within 1 month prior to randomization) or current administration of any
immunosuppressive medications (including oral, inhaled or systemically injected
steroids) and use of any investigational agents, including any agents that impact the
immune response or the cytokine system;
18. condition which interferes with the ability to accurately determine glycated HbA1c.
Examples include: Genetic variants (e.g. HbS trait, HbC trait), elevated fetal
hemoglobin (HbF) and chemically modified derivatives of hemoglobin (e.g. carbamylated
Hb in patients with renal failure); Any condition that shortens erythrocyte survival
or decreases mean erythrocyte age (e.g., recovery from acute blood loss, hemolytic
anemia); Iron deficiency anemia, iron replacement therapy;
19. significant systemic infection during the 4 weeks before the first dose of study drug
(e.g., infection requiring hospitalization, major surgery, or i.v. antibiotics to
resolve; other infections, e.g., bronchitis, sinusitis, localized cellulitis,
candidiasis, or urinary tract infections, must be assessed on a case-bycase basis by
the investigator regarding whether they are serious enough to warrant exclusion).
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