The Research Institute Of The Mcgill University Health Centre

HUMAN GENETICS OF TB RESISTANCE IN HIV-INFECTED PERSONS

TAKE-IT TOO: TEEN ADHERENCE IN KIDNEY TRANSPLANT IMPROVING TRACKING TO OPTIMIZE OUTCOMES

WIRELESS MICROSENSOR TO CONTINUOUSLY MONITOR COMPARTMENT PRESSURE IN TRAUMA VICTIMS

MOLECULAR AND GENETIC EPIDEMIOLOGY OF LP(A)-MEDIATED CALCIFIC AORTIC VALVE DISEASE

PRECISION NUTRITION INCREASES EFFICACY OF DNA-DAMAGING THERAPIES IN PROSTATE CANCER

A GENOMICS APPROACH TO STUDY MOLECULAR HETEROGENEITY IN THE PATHOGENESIS OF TYPE 2 DIABETES AND ITS COMPLICATIONS

IDENTIFYING DRIVERS OF THERAPY RESISTANCE WITHIN THE TUMOR MICROENVIRONMENT OF ESOPHAGEAL ADENOCARCINOMA

DEVELOPMENT OF NEW THERAPEUTICS TARGETING BIOFILM FORMATION BY THE OPPORTUNISTIC PULMONARY PATHOGENS PSEUDOMONAS AERUGINOSA AND ASPERGILLUS FUMIGATUS

IDENTIFICATION OF PROSTATE CANCER PROGNOSTIC MARKERS

ROLE OF BENZODIAZEPINE RECEPTOR IN LEYDIG CELL FUNCTION

DEVELOPMENT OF CD109 AS A NOVEL TGF-BETA ANTAGONIST AND ANTI-FIBROTIC AGENT FOR THE TREATMENT OF SCLERODERMA

USP19 AS A NOVEL THERAPEUTIC TARGET FOR IMPEDING PROPAGATION AND SECRETION OF TAU IN PARKINSON'S DISEASE

REMOVING BARRIERS TO FULL RECOVERY

PARATHYROID HORMONE-RELATED PEPTIDE (PTHRP) AS A NEW TARGET FOR METASTATIC BREAST CANCER: EVALUATION IN PRECLINICAL MODELS

STAT6-DEPENDENT BRIDGING OF INNATE AND TH2 ADAPTIVE IMMUNITY IN THE LUNG

NETWORK FOR RARE TUMORS OF THE OVARY (NRTO)

FETAL ORIGIN OF MALE REPRODUCTIVE DISORDERS

PROTECTIVE EFFECT OF FENRETINIDE AGAINST SPINAL CONTUSION INJURY

DISCREET AND WEARABLE MICROWAVE SENSING FOR CONTINUOUS REAL-TIME BLADDER MONITORING

THE ROLE OF OSR1 IN BLADDER DYSFUNCTION FROM SPINAL CORD INJURY

BUILDING A RAPID DRUG DISCOVERY PIPELINE SPECIFIC FOR PEDIATRIC ACUTE MYELOGENOUS LEUKEMIA WITH MACHINE LEARNING/IN VITRO FEEDBACK LOOPS

STAT6-DEPENDENT BRIDGING OF INNATE AND TH2 ADAPTIVE IMMUNITY IN THE LUNG

EXPLORE THE IMPACT OF MICROBIOME IN THE RESPONSE OF THE COMBINATION OF RADIATION WITH IMMUNE CHECKPOINT BLOCKADE IN MUSCLE-INVASIVE BLADDER CANCER

ALLEVIATING CARBOHYDRATE COUNTING IN ADULTS WITH TYPE 1 DIABETES WITH?WEEKLY SEMAGLUTIDE INJECTIONS ADDED TO?AN?AUTOMATED INSULIN DELIVERY WITH LYUMJEV - PROJECT SUMMARY/ABSTRACT ONE OF THE MAIN CHALLENGES IN MAINTAINING TIGHT GLUCOSE CONTROL IN INDIVIDUALS WITH TYPE 1 DIABETES (T1D) OCCURS AT MEALTIMES. CURRENT INTENSIVE INSULIN THERAPY IN T1D INVOLVES PRANDIAL INSULIN BOLUSES DEPENDENT ON THE CARBOHYDRATE CONTENT OF THE INGESTED MEAL. HOWEVER, ACCURATE CARBOHYDRATE COUNTING IS A CHALLENGING AND BURDENSOME TASK FOR MANY INDIVIDUALS WITH T1D. IN THIS PROPOSAL, WE AIM TO SIMPLIFY MEALTIME DIABETES MANAGEMENT WITH A COMBINATION OF GLUCOSE- LOWERING DRUGS AND OUR AUTOMATED INSULIN DELIVERY (AID) SYSTEM USING LYUMJEV. GLUCAGON-LIKE-PEPTIDE-1 IS A HORMONE RELEASED BY GUT ENDOCRINE CELLS IN RESPONSE TO GLUCOSE CONSUMPTION. EXOGENOUS GLP-1 RECEPTOR AGONISTS (GLP-1 RAS) HAVE BEEN DEVELOPED TO DECREASE FASTING AND POSTPRANDIAL BLOOD GLUCOSE BY (I) INCREASING INSULIN SECRETION, (II) DECREASING GLUCAGON SECRETION, (III) SLOWING GASTRIC EMPTYING, AND (IV) REDUCING APPETITE BY STIMULATING SATIETY BRAIN CENTERS. RANDOMIZED CONTROLLED TRIALS IN TYPE 2 DIABETES HAVE SHOWN THAT GLP-1 RAS IMPROVE GLUCOSE CONTROL WITHOUT INCREASING HYPOGLYCEMIA, AND RECENT DATA IN TYPE 1 DIABETES HAVE ALSO SHOWN PROMISING RESULTS. LYUMJEV IS A NOVEL ULTRA-RAPID INSULIN LISPRO FORMULATION WITH A FASTER ONSET OF INSULIN ACTION COMPARED TO THE CONVENTIONAL INSULIN LISPRO – HUMALOG. DELIVERING LYUMJEV AT MEALTIMES SIGNIFICANTLY LOWERS POSTPRANDIAL GLUCOSE LEVELS AND REDUCES POST-MEAL INCREMENTAL AREA UNDER THE CURVE COMPARED TO HUMALOG. WE AIM TO CONDUCT A 2 × 2 FACTORIAL, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND, CROSSOVER TRIAL TO ASSESS IF THE ADDITION OF SEMAGLUTIDE TO AN AID SYSTEM WITH LYUMJEV CAN ALLEVIATE THE BURDEN OF CARBOHYDRATE COUNTING, WITHOUT DEGRADING DAYTIME GLUCOSE CONTROL IN 26 ADULTS WITH T1D. THE STUDY WILL CONSIST OF 4 INTERVENTIONS, EACH 4-WEEKS IN LENGTH, TESTING SEMAGLUTIDE-PLUS-LYUMJEV WITH (I) A SYSTEM THAT REQUIRES CARB COUNTING (AID-COUNT) AND (II) A SYSTEM THAT REQUIRES MEAL ANNOUNCEMENT ONLY (AID-ANNOUNCE), AS WELL AS PLACEBO-PLUS-LYUMJEV WITH (III) AID-COUNT AND (IV) AID-ANNOUNCE. THE ORDER OF THE OF THE DRUG SEQUENCE (SEMAGLUTIDE VS PLACEBO) WILL BE RANDOMIZED 1:1. WITHIN EACH DRUG SEQUENCE, THE ORDER OF THE AID CONFIGURATION WILL ALSO BE RANDOMIZED 1:1. AT THE START OF EACH DRUG SEQUENCE, 12-WEEK DOSE TITRATION PERIOD WILL BE INITIATED. A 2-WEEK WASHOUT PERIOD WILL BE APPLIED BETWEEN THE DRUG SEQUENCES. THE PRIMARY OUTCOME IS THE DAYTIME (6:00-24:00) PERCENTAGE OF TIME SPENT IN THE TARGET GLUCOSE RANGE (TIR), DEFINED AS 70-180MG/DL, OVER 4 WEEKS BETWEEN SEMA-PLUS-LYUMJEV-AID-ANNOUNCE AND PLACEBO-PLUS- LYUMJEV-AID-COUNT (CONTROL ARM). WE HYPOTHESIZE THAT SEMA-PLUS-LYUMJEV-AID-ANNOUNCE WILL ACHIEVE NON-INFERIOR DAYTIME TIR COMPARED TO THE CONTROL ARM. PAGE 1 OF 1

DEVELOPING NEXT GENERATION OF PROGNOSTIC TOOLS FOR LOCALIZED CLEAR CELL RENAL CELL CARCINOMA THROUGH INTEGRATION OF GENOMIC, CLINICAL, AND PATHOLOGICAL FEATURES

ESTABLISHING THE FOUNDATION FOR COMMUNICATION BETWEEN THE OOCYTE AND ITS FOLLICULAR MICROENVIRONMENT: A NEW DYNAMIC MODEL

NOVEL AMINOGLYCOSIDE THERAPY OF NONSENSE MUTATIONS IN POLYCYSTIC KIDNEY DISEASE

PREVENTION AND TREATMENT OF FOOD ALLERGY THROUGH STAT6-IP MEDIATED IMMUNOMODULATION

FECAL BIOMARKERS IN CLOSTRIDIUM DIFFICILE INFECTION

CONTRIBUTION OF THE HEPATIC CYTOPLASMIC LIPID DROPLET TO THE DEVELOPMENT OF DIABETES MELLITUS TYPE 2

BACTERIA DERIVED SMALL MOLECULES AS NOVEL ANTIMICROBIAL ADJUVANTS FOR THE TREATMENT OF NOSOCOMIAL AND DRUG-RESISTANT BACTERIAL INFECTIONS

BRAIN MATURATION TRAJECTORIES IN INFANTS FOLLOWING AND OPEN HEART SURGERY

POLLUTION, EPIGENETICS, AND SEROLOGIC MARKERS OF RHEUMATOID ARTHRITIS

CANCER RISK: ADVANCING KNOWLEDGE IN SYSTEMIC RHEUMATIC DISEASE

PHONOMYOGRAPHY AS A NONINVASIVE CONTINUOUS MONITORING TECHNIQUE FOR ACUTE COMPARTMENT SYNDROME IN MILITARY TRAUMA PATIENTS

SOY-RICH DIET FOR PREVENTING CHRONIC POST BREAST CANCER SURGERY PAIN

CANCER RISK IN PEDIATRIC-ONSET RHEUMATIC DISEASE