R01DK142666

REAL WORLD USE OF ANTI-OBESITY MEDICATIONS TO TREAT ADOLESCENT OBESITY: MOVING BEYOND THE CLINICAL TRIAL - PROJECT SUMMARY/ABSTRACT ONE IN FIVE US ADOLESCENTS HAVE OBESITY, MAKING PEDIATRIC OBESITY A SIGNIFICANT PUBLIC HEALTH PROBLEM. SAFE AND EFFECTIVE TREATMENT OPTIONS EXIST FOR ADOLESCENTS WITH OBESITY INCLUDING MOTIVATIONAL INTERVIEWING, INTENSIVE HEALTH BEHAVIOR AND LIFESTYLE THERAPY, PHARMACOTHERAPY, AND METABOLIC AND BARIATRIC SURGERY. RECENTLY, SEVERAL ANTI- OBESITY MEDICATIONS (AOMS) HAVE BEEN APPROVED FOR USE IN ADOLESCENTS, SHOWING GREAT PROMISE FOR REDUCING OBESITY. HOWEVER, TO DATE, THESE AOMS HAVE ONLY BEEN STUDIED IN TIGHTLY CONTROLLED CLINICAL TRIALS. WHILE CLINICAL TRIALS HAVE HIGH INTERNAL VALIDITY AND PROVIDE EVIDENCE FOR EFFICACY OF PHARMACOLOGICAL APPROACHES, THEY ARE LIMITED IN THEIR EXTERNAL VALIDITY AND REAL-WORLD GENERALIZABILITY. THIS HAS LEAD TO GAPS IN OUR UNDERSTANDING OF ADOLESCENT AOM USE INCLUDING KNOWLEDGE OF THE REACH OF AOMS IN YOUTH, EFFECTIVENESS WITHIN REAL-WORLD CLINICAL SETTINGS, AND POSSIBLE UNINTENDED CONSEQUENCES OF AOM USE. IT IS IMPERATIVE THAT THESE GAPS ARE ADDRESSED TO ENSURE THAT ADOLESCENTS RECEIVE SAFE AND EFFECTIVE CLINICAL CARE. THEREFORE, THE OBJECTIVE OF THIS PROJECT IS TO COLLECT REAL- WORLD EVIDENCE THAT CAN BE USED TO INFORM CLINICAL PRACTICE, IMPROVE HEALTH OUTCOMES, AND ENSURE PATIENT SAFETY AMONG ADOLESCENTS USING AOMS. THE PROPOSED PROJECT WILL RECRUIT A COHORT OF ADOLESCENTS USING AOMS (12-17Y; N=200) FROM TWO PEDIATRIC OBESITY TREATMENT CLINICS. IN AIM 1, WE WILL CHARACTERIZE THE POPULATION OF YOUTH USING AOMS BY EXAMINING DEMOGRAPHIC CHARACTERISTICS FROM THE ELECTRONIC HEALTH RECORD OF COHORT YOUTH COMPARED TO THOSE WHO ARE ELIGIBLE, BUT NEVER PRESCRIBED AOMS. IN AIMS 2 & 3, COHORT PARTICIPANTS WILL BE FOLLOWED FOR 18- MONTHS, COMPLETING FOUR STUDY VISITS THAT WILL INCLUDE MEASURE OF BODY COMPOSITION, DIET, PHYSICAL ACTIVITY, MENTAL HEALTH AND QUALITY OF LIFE. A SUBSET OF PATIENTS WILL COMPLETE DXA SCANS TO FURTHER ASSESS CHANGES IN BODY COMPOSITION AND SEMI-STRUCTURED INTERVIEWS TO YIELD RICHER CONTEXTUAL INFORMATION. DATA WILL ALSO BE OBTAINED FROM THE ELECTRONIC HEALTH RECORD AND ASSESSMENTS OF ADHERENCE THROUGHOUT THE DURATION OF COHORT PARTICIPATION. IN AIM 2, EFFECTIVENESS OF AOMS WILL BE EVALUATED BY EXAMINING CHANGE IN RELATIVE BMI AMONG COHORT YOUTH COMPARED TO THE YOUTH NOT UTILIZING AOMS FROM AIM 1 USING PROPENSITY WEIGHTING APPROACHES. ADDITIONAL ANALYSES WILL EXAMINE THE RELATIONSHIP BETWEEN CHANGES IN DIET, PHYSICAL ACTIVITY AND STUDY OUTCOMES AS WELL DESCRIBE ADHERENCE TO AOM TREATMENT PROTOCOLS INCLUDING MEDICATION SWITCHING AND DISCONTINUATION. IN AIM 3, WE WILL CONSIDER THE UNINTENDED CONSEQUENCES OF AOM USE INCLUDING LONGITUDINAL CHANGES IN MENTAL HEALTH, DEVELOPMENT OF DISORDERED EATING BEHAVIOR, AND CHANGES IN DXA MEASURED BODY COMPOSITION AND BONE MINERAL DENSITY. OVERALL, THIS PROJECT WILL PROVIDE VALUABLE CLINICAL EVIDENCE AROUND AOM USE IN ADOLESCENTS BY ADDRESSING KEY GAPS IN OUR KNOWLEDGE OF ACCESS, EFFECTIVENESS AND FACTORS THAT INFLUENCE EFFECTIVENESS, AND POTENTIAL UNINTENDED CONSEQUENCES. SUCCESSFUL COMPLETION OF THIS PROJECT WILL INFORM CLINICAL RECOMMENDATIONS AROUND ADOLESCENT AOM USE AND HAS BROADER IMPLICATIONS FOR IMPLEMENTATION OF AOMS AMONG SPECIALIZED OBESITY TREATMENT CENTERS AND GENERAL PEDIATRIC CLINICS.

Duke University

(1) TO PROMOTE EXTRAMURAL BASIC AND CLINICAL BIOMEDICAL RESEARCH THAT IMPROVES THE UNDERSTANDING OF THE MECHANISMS UNDERLYING DISEASE AND LEADS TO IMPROVED PREVENTIONS, DIAGNOSIS, AND TREATMENT OF DIABETES, DIGESTIVE, AND KIDNEY DISEASES. PROGRAMMATIC AREAS WITHIN THE NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES INCLUDE DIABETES, DIGESTIVE, ENDOCRINE, HEMATOLOGIC, LIVER, METABOLIC, NEPHROLOGIC, NUTRITION, OBESITY, AND UROLOGIC DISEASES. SPECIFIC PROGRAMS AREAS OF INTEREST INCLUDE THE FOLLOWING: (A) FOR DIABETES, ENDOCRINE, AND METABOLIC DISEASES AREAS: FUNDAMENTAL AND CLINICAL STUDIES INCLUDING THE ETIOLOGY, PATHOGENESIS, PREVENTION, DIAGNOSIS, TREATMENT AND CURE OF DIABETES MELLITUS AND ITS COMPLICATIONS, NORMAL AND ABNORMAL FUNCTION OF THE PITUITARY, THYROID, PARATHYROID, ADRENAL, AND OTHER HORMONE SECRETING GLANDS, HORMONAL REGULATION OF BONE, ADIPOSE TISSUE, AND LIVER, ON FUNDAMENTAL ASPECTS OF SIGNAL TRANSDUCTION, INCLUDING THE ACTION OF HORMONES, COREGULATORS, AND CHROMATIN REMODELING PROTEINS, HORMONE BIOSYNTHESIS, SECRETION, METABOLISM, AND BINDING, AND ON HORMONAL REGULATION OF GENE EXPRESSION AND THE ROLE(S) OF SELECTIVE RECEPTOR MODULATORS AS PARTIAL AGONISTS OR ANTAGONISTS OF HORMONE ACTION, AND FUNDAMENTAL STUDIES RELEVANT TO METABOLIC DISORDERS INCLUDING MEMBRANE STRUCTURE, FUNCTION, AND TRANSPORT PHENOMENA AND ENZYME BIOSYNTHESIS, AND BASIC AND CLINICAL STUDIES ON THE ETIOLOGY, PATHOGENESIS, PREVENTION, AND TREATMENT OF INHERITED METABOLIC DISORDERS (SUCH AS CYSTIC FIBROSIS). (B) FOR DIGESTIVE DISEASE AND NUTRITION AREAS: GENETICS AND GENOMICS OF THE GI TRACT AND ITS DISEASES, GENETICS AND GENOMICS OF LIVER/PANCREAS AND DISEASES, GENETICS AND GENOMICS OF NUTRITION, GENETICS AND GENOMICS OF OBESITY, BARIATRIC SURGERY, CLINICAL NUTRITION RESEARCH, CLINICAL OBESITY RESEARCH, COMPLICATIONS OF CHRONIC LIVER DISEASE, FATTY LIVER DISEASE, GENETIC LIVER DISEASE, HIV AND LIVER, CELL INJURY, REPAIR, FIBROSIS AND INFLAMMATION IN THE LIVER, LIVER CANCER, LIVER TRANSPLANTATION, PEDIATRIC LIVER DISEASE, VIRAL HEPATITIS AND INFECTIOUS DISEASES, GASTROINTESTINAL AND NUTRITION EFFECTS OF AIDS, GASTROINTESTINAL MUCOSAL AND IMMUNOLOGY, GASTROINTESTINAL MOTILITY, BASIC NEUROGASTROENTEROLOGY, GASTROINTESTINAL DEVELOPMENT, GASTROINTESTINAL EPITHELIAL BIOLOGY, GASTROINTESTINAL INFLAMMATION, DIGESTIVE DISEASES EPIDEMIOLOGY AND DATA SYSTEMS, NUTRITIONAL EPIDEMIOLOGY AND DATA SYSTEMS, AUTOIMMUNE LIVER DISEASE, BILE, BILIRUBIN AND CHOLESTASIS, BIOENGINEERING AND BIOTECHNOLOGY RELATED TO DIGESTIVE DISEASES, LIVER, NUTRITION AND OBESITY, CELL AND MOLECULAR BIOLOGY OF THE LIVER, DEVELOPMENTAL BIOLOGY AND REGENERATION, DRUG-INDUCED LIVER DISEASE, GALLBLADDER DISEASE AND BILIARY DISEASES, EXOCRINE PANCREAS BIOLOGY AND DISEASES, GASTROINTESTINAL NEUROENDOCRINOLOGY, GASTROINTESTINAL TRANSPORT AND ABSORPTION, NUTRIENT METABOLISM, PEDIATRIC CLINICAL OBESITY, CLINICAL TRIALS IN DIGESTIVE DISEASES, LIVER CLINICAL TRIALS, OBESITY PREVENTION AND TREATMENT, AND OBESITY AND EATING DISORDERS. (C) FOR KIDNEY, UROLOGIC AND HEMATOLOGIC DISEASES AREAS: STUDIES OF THE DEVELOPMENT, PHYSIOLOGY, AND CELL BIOLOGY OF THE KIDNEY, PATHOPHYSIOLOGY OF THE KIDNEY, GENETICS OF KIDNEY DISORDERS, IMMUNE MECHANISMS OF KIDNEY DISEASE, KIDNEY DISEASE AS A COMPLICATION OF DIABETES, EFFECTS OF DRUGS, NEPHROTOXINS AND ENVIRONMENTAL TOXINS ON THE KIDNEY, MECHANISMS OF KIDNEY INJURY REPAIR, IMPROVED DIAGNOSIS, PREVENTION AND TREATMENT OF CHRONIC KIDNEY DISEASE AND END-STAGE RENAL DISEASE, IMPROVED APPROACHES TO MAINTENANCE DIALYSIS THERAPIES, BASIC STUDIES OF LOWER URINARY TRACT CELL BIOLOGY, DEVELOPMENT, PHYSIOLOGY, AND PATHOPHYSIOLOGY, CLINICAL STUDIES OF BLADDER DYSFUNCTION, INCONTINENCE, PYELONEPHRITIS, INTERSTITIAL CYSTITIS, BENIGN PROSTATIC HYPERPLASIA, UROLITHIASIS, AND VESICOURETERAL REFLUX, DEVELOPMENT OF NOVEL DIAGNOSTIC TOOLS AND IMPROVED THERAPIES, INCLUDING TISSUE ENGINEERING STRATEGIES, FOR UROLOGIC DISORDERS,RESEARCH ON HEMATOPOIETIC CELL DIFFERENTIATION, METABOLISM OF IRON OVERLOAD AND DEFICIENCY, STRUCTURE, BIOSYNTHESIS AND GENETIC REGULATION OF HEMOGLOBIN, AS WELL AS RESEARCH ON THE ETIOLOGY, PATHOGENESIS, AND THERAPEUTIC MODALITIES FOR THE ANEMIA OF INFLAMMATION AND CHRONIC DISEASES. (2) TO ENCOURAGE BASIC AND CLINICAL RESEARCH TRAINING AND CAREER DEVELOPMENT OF SCIENTISTS DURING THE EARLY STAGES OF THEIR CAREERS. THE RUTH L. KIRSCHSTEIN NATIONAL RESEARCH SERVICE AWARD (NRSA) FUNDS BASIC AND CLINICAL RESEARCH TRAINING, SUPPORT FOR CAREER DEVELOPMENT, AND THE TRANSITION FROM POSTDOCTORAL BIOMEDICAL RESEARCH TRAINING TO INDEPENDENT RESEARCH RELATED TO DIABETES, DIGESTIVE, ENDOCRINE, HEMATOLOGIC, LIVER, METABOLIC, NEPHROLOGIC, NUTRITION, OBESITY, AND UROLOGIC DISEASES. (3) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM. THE SBIR PROGRAM AIMS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO ENHANCE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. (4) TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM. THE STTR PROGRAM INTENDS TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.847 - Diabetes, Digestive, and Kidney Diseases Extramural Research

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [HHS - NIH]

North Carolina United States

State-Wide

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)