课题基金 / 基金详情

Long term efficacy and safety of orlistat for type 1 hyperlipoproteinemia: a randomized, double-blind, placebo-controlled trial

Long term efficacy and safety of orlistat for type 1 hyperlipoproteinemia: a randomized, double-blind, placebo-controlled trial
奥利司他治疗 1 型高脂蛋白血症的长期疗效和安全性:一项随机、双盲、安慰剂对照试验
批准号:
10570530
负责人:
Abhimanyu Garg
金额:
$55.06万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
已结题
起止时间:
2023-06-01 至 2024-05-31
关键词:
9 year oldAdmission activityAdultApolipoproteinsAtherosclerosisBody WeightChemistryChildCirrhosisClinicalClinical ResearchClinical TrialsConsumptionCoronary heart diseaseCross-Over StudiesCross-Over TrialsDataDependovirusDevelopmentDiabetes MellitusDiagnosisDietary FatsDiseaseDocosahexaenoic AcidsDouble-Blind MethodEicosapentaenoic AcidEnrollmentEquilibriumEvaluationExcretory functionFamilial HypercholesterolemiaFamilial Lipoprotein Lipase DeficiencyFastingFat-Restricted DietFat-Soluble VitaminFatty acid glycerol estersFibratesFish OilsHepaticHepatosplenomegalyHourHyperlipoproteinemiaHypertriglyceridemiaInpatientsIntestinesLifeLipaseLipoproteinsLiverLongitudinal StudiesLoss of HeterozygosityLow-Density LipoproteinsMarketingMeasuresMetabolic DiseasesMineralsModelingMorbidity - disease rateNephrolithiasisNicotinic AcidsOmega-3 Fatty AcidsOutcomeOxalatesPancreasPatientsPharmaceutical PreparationsPhasePlacebo ControlPlacebosPlasmapheresisPrevalenceProceduresProteinsQuality of lifeQuestionnairesRandomizedRecurrenceReportingResearch DesignResearch PersonnelRiskSafetySerumSpleenSteatorrheaStomachSyndromeTestingThrombocytopeniaTimeToxic effectTriglyceridesUnited States Food and Drug AdministrationUrineVariantXanthomasabsorptionacute pancreatitisapolipoprotein B-48autosomechronic pancreatitisdiacylglycerol O-acyltransferasedietarydouble-blind placebo controlled trialearly childhoodeffective therapyfecal microbiotagastrointestinalgastrointestinal symptomgene therapyinfancyinhibitorlipoprotein lipaseloss of functionmalemanmicrosomal triglyceride transfer proteinmortalitynovel therapeuticsolder womenopen labelorlistatpreventprimary endpointscreeningsecondary endpointside effecttrial design

项目摘要

项目成果

Abhimanyu Garg的其他基金

相关文献

中文摘要
翻译
摘要
英文摘要
Abstract Type I hyperlipoproteinemia (T1HLP, also known as familial chylomicronemia syndrome or FCS) is a rare, autosomal recessive metabolic disorder characterized by extreme hypertriglyceridemia due to a deficiency of lipoprotein lipase or related proteins. Treatment of these patients is challenging as conventional triglyceride- lowering medications, such as fibrates and fish oil, are ineffective. An extremely low fat diet is helpful, however, despite good dietary compliance, some patients continue to have severe hypertriglyceridemia and recurrent pancreatitis which can be life threatening. There is a pressing need for developing novel therapeutic options for these patients, as currently, there is no FDA approved medication. Our recent preliminary data from a randomized, open-label, clinical trial of orlistat (an inhibitor of intestinal lipase) with a four-period, two- sequence (“orlistat” and “off orlistat” for 3 months), crossover study design in two young males (11 and 9 years old) with T1HLP revealed more than 50% reduction in fasting serum triglycerides with only minimal side effects. However, the long-term efficacy and safety of orlistat therapy for children and adults with T1HLP remains unknown. Potential complications of long-term orlistat use include deficiencies in fat soluble vitamins, steatorrhea, hyperoxaluric nephrolithiasis, and alteration in fecal microbiota. Therefore, we wish to study the long-term efficacy and safety of orlistat for reducing serum triglyceride levels in patients with T1HLP. We plan to enroll 28 patients with T1HLP (fasting serum triglycerides ≥ 1,000 mg/dL) in a randomized, double-blind, placebo-controlled, cross-over trial with an open-label extension. After a screening evaluation, the subjects will be advised to consume an extremely low fat diet (≤15% of total energy from fat) for the entire duration of the study. After the baseline period of 8 weeks, they will be randomly assigned to placebo or orlistat for the duration of 24 weeks (Phase 1). After Phase 1, all patients will enter an open-label extension (Phase 2) and receive orlistat for a period of 24 weeks for a total duration of 48 weeks. During the last week of Baseline Period, Phase 1, and at 24 weeks of Phase 2, patients will be admitted to the in-patient Clinical Research Unit for 4 days to measure serum lipoproteins and chemistry panel for 3 consecutive days, fat-soluble vitamin levels, 24 hour urine oxalate and stone risk profile, mineral balance, 72 hour fecal fat, fecal microbiota, hepatic triglyceride, liver and spleen volume, and will complete gastrointestinal and quality of life questionnaires. The primary endpoint will be fasting serum triglycerides. The secondary endpoint variables will be apolipoprotein B-48 levels, liver fat content and volume. Safety will be assessed by measuring fat soluble vitamins levels, body weight, quality of life, gastrointestinal symptoms, oxalic aciduria, fecal fat excretion and fecal microbiota. Generalized linear mixed models will be used for statistical comparisons. Our data will determine long-term safety and efficacy of orlistat therapy for patients with T1HLP and orlistat may become the first line therapy as an adjunct to extremely low fat diet in these patients.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Genetic and Metabolic Basis of Familial Lipodystrophies
  • 批准号:
    10119702
  • 项目类别:
  • 资助金额:
    $68.84万
  • 财政年份:
    2015
  • 负责人:
    Abhimanyu Garg
  • 依托单位:
Genetic and Metabolic Basis of Familial Lipodystrophies
  • 批准号:
    9054839
  • 项目类别:
  • 资助金额:
    $56.1万
  • 财政年份:
    2015
  • 负责人:
    Abhimanyu Garg
  • 依托单位:
Genetic and Metabolic Basis of Familial Lipodystrophies
  • 批准号:
    9237269
  • 项目类别:
  • 资助金额:
    $55.44万
  • 财政年份:
    2015
  • 负责人:
    Abhimanyu Garg
  • 依托单位:
Genetic and Metabolic Basis of Familial Lipodystrophies
  • 批准号:
    10264148
  • 项目类别:
  • 资助金额:
    $69.05万
  • 财政年份:
    2015
  • 负责人:
    Abhimanyu Garg
  • 依托单位: