[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT04320264":3,"trial-entities:NCT04320264":132,"trial-summary:NCT04320264":136},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":6,"overall_status":7,"completion_date":8,"status_verified_date":9,"last_update_date":10,"start_date":11,"sponsor_name":12,"lead_sponsor_class":13,"has_dmc":14,"brief_summary":15,"detailed_description":16,"conditions":17,"keywords":19,"study_type":22,"primary_purpose":23,"phases":24,"enrollment_info":25,"interventions":28,"primary_outcomes":35,"secondary_outcomes":55,"sex":62,"minimum_age":63,"maximum_age":64,"healthy_volunteers":14,"eligibility_criteria":65,"std_ages":86,"locations":88,"central_contacts":107,"overall_officials":110,"references":114,"see_also_links":131},"NCT04320264","UMCIRB 19-000914","Metabolic Inflexibility is Related to Elevated Muscle Anaerobic Glycolysis","RECRUITING","2025-12","2025-08","2025-08-07","2020-03-03","East Carolina University","OTHER",false,"The focus of this proposal is on overweight (25\\>BMI\\\u003C30 kg\u002Fm2) subjects, as these individuals exhibit a high risk of becoming obese and\u002For developing metabolic diseases. We hypothesize that in some overweight individuals there is a \"metabolic program\" in skeletal muscle which predisposes them to the development of obesity. Findings may lead to clinical screening tools for determining risk for obesity in non-obese individuals and targeting this group for prevention.","Our overall hypothesis is that increased reliance on anaerobic glycolysis in muscle shifts fasting metabolism from fat towards carbohydrate utilization, which results in metabolic inflexibility and subsequent metabolic disease (i.e. obesity). To test our hypothesis, overweight subjects (BMI 25 to 30 kg\u002Fm2) will be recruited and screened for reliance on anaerobic glycolysis (resting\u002Ffasting plasma lactate concentrations). Subjects with high (top quartile) and low (bottom quartile) resting\u002Ffasting plasma lactate will be chosen. The premise of this screening is that subjects with low lactate will have high muscle aerobic substrate oxidation, while those with elevated lactate will have low muscle oxidative metabolism. Severely obese subjects will be studied as a comparator group. In aim 1 in vivo muscle lactate release and respiratory exchange ratio (RER) will be determined to investigate if subjects with high reliance on anaerobic glycolysis exhibit a shift towards carbohydrate utilization at the whole-body level. Aim 2 will test whether subjects with elevated reliance on anaerobic glycolysis in muscle are metabolically inflexible. To establish causality, aim 3 is designed to follow subjects after an intervention that shifts skeletal muscle metabolism from carbohydrate to fat utilization. Our preliminary findings indicate that bariatric surgery normalizes muscle lactate production; therefore, severely obese subjects will be studied before and after gastric bypass surgery (aim 3).\n\nThe study (MetFlex) will enroll 74 adults; (Group 1) 60 overweight (BMI 25 to 30 kg\u002Fm2) males and females ages 18-50 years old and (Group 2) 14 severely obese (BMI 40 to 50 kg\u002Fm2) adult females who are scheduled for bariatric surgery.\n\nEndpoints to be investigated in the 3 specific aims.\n\nCarbohydrate\u002Ffat oxidation (RER) in the fasting condition. High lactate vs low lactate groups (aim 1). Pre-surgery vs post-surgery (aim 3)\n\nMuscle oxygen consumption (substrate oxidation) in the fasting condition. High lactate vs low lactate groups (aim 1). Pre-surgery vs post-surgery (aim 3)\n\nMuscle lactate release in the fasting condition. High lactate vs low lactate groups (aim 1). Pre-surgery vs post-surgery (aim 3)\n\nEndogenous glucose production in the fasting condition. High lactate vs low lactate groups (aim 1). Pre-surgery vs post-surgery (aim 3)\n\nInsulin sensitivity (clamp M value). High lactate vs low lactate groups (aim 1)\n\nChange in Carbohydrate\u002Ffat oxidation (RER) in response to glucose + insulin (metabolic flexibility). High lactate vs low lactate groups (aim 2)\n\nChange in muscle fat oxidation in response to high fat feeding (metabolic flexibility). High lactate vs low lactate groups (aim 2)\n\nChange in muscle oxygen consumption (substrate oxidation) in response to high fat feeding (metabolic flexibility). High lactate vs low lactate groups (aim 2)\n\nOur basic premise is that elevated fasting plasma lactate causes glucose production to be increased and that a \"Vicious Cori cycle\" is the underlying cause of the metabolic syndrome.",[18],"Metabolic Inflexibility",[18,20,21],"Obesity","Anaerobic glycolysis","OBSERVATIONAL",null,[],{"count":26,"type":27},100,"ESTIMATED",[29],{"type":30,"name":31,"description":32,"armGroupLabels":33},"PROCEDURE","Weight loss surgery","Severely obese women (BMI \\>40) undergo sleeve gastrectomy",[34],"Obese",[36,40,43,46,49,52],{"measure":37,"description":38,"timeFrame":39},"Carbohydrate\u002Ffat oxidation (RER) in the fasting condition.","RER will be measured from indirect calorimetry","Years 1-5",{"measure":41,"description":42,"timeFrame":39},"Muscle oxygen consumption (substrate oxidation) in the fasting condition.","Muscle oxygen consumption will be measured by near-infrared spectroscopy (NIRS)",{"measure":44,"description":45,"timeFrame":39},"Muscle lactate release in the fasting condition.","Muscle lactate release will be measured by microdialysis",{"measure":47,"description":48,"timeFrame":39},"Change in Carbohydrate\u002Ffat oxidation (RER) in response to glucose + insulin (metabolic flexibility)","Indirect calorimetry during glucose clamp",{"measure":50,"description":51,"timeFrame":39},"Change in muscle fat oxidation in response to high fat feeding (metabolic flexibility).","Oxidation of fatty acid in muscle homogenate.",{"measure":53,"description":54,"timeFrame":39},"Change in muscle oxygen consumption (substrate oxidation) in response to high fat feeding (metabolic flexibility).","Oxygen consumption measured by near-infrared spectroscopy (NIRS)",[56,59],{"measure":57,"description":58,"timeFrame":39},"Insulin sensitivity (clamp M value).","Measured during glucose clamp.",{"measure":60,"description":61,"timeFrame":39},"Endogenous glucose production in the fasting condition.","Measured with isotopically labeled glucose","ALL","18 Years","50 Years",{"inclusion":66,"exclusion":71,"raw_text":85},[67,68,69,70],"18-50 years old","BMI of 25 - 30 kg\u002Fm2","BMI \\> 40kg\u002Fm2","Lactate levels in top and lower 25%",[72,73,74,75,76,77,78,79,80,81,82,83,84],"Pregnant women","Mentally disabled","Prisoners","Smokers","Subjects with heart disease","Type 1 and 2 diabetes","Endocrine disease","Hypertension","Musculoskeletal disease","Peripheral occlusion","Hepatic disease","Have had weight fluctuations exceeding + 3% in the previous 12 months","On medications which alter carbohydrate metabolism will not be studied","Inclusion Criteria:\n\n* 18-50 years old\n* BMI of 25 - 30 kg\u002Fm2\n* BMI \\> 40kg\u002Fm2\n* Lactate levels in top and lower 25%\n\nExclusion Criteria:\n\n* Pregnant women\n* Mentally disabled\n* Prisoners\n* Smokers\n* Subjects with heart disease\n* Type 1 and 2 diabetes\n* Endocrine disease\n* Hypertension\n* Musculoskeletal disease\n* Peripheral occlusion\n* Hepatic disease\n* Have had weight fluctuations exceeding + 3% in the previous 12 months\n* On medications which alter carbohydrate metabolism will not be studied",[87],"ADULT",[89],{"facility":12,"status":7,"city":90,"state":91,"zip":92,"country":93,"contacts":94,"geoPoint":104},"Greenville","North Carolina","27834","United States",[95,100],{"name":96,"role":97,"phone":98,"email":99},"Terry Jones, PhD","CONTACT","2527446249","joneste@ecu.edu",{"name":101,"role":97,"phone":102,"email":103},"Nicholas Broskey, PhD","2527374684","broskeyn19@ecu.edu",{"lat":105,"lon":106},35.61266,-77.36635,[108,109],{"name":96,"role":97,"phone":98,"email":99},{"name":101,"role":97,"phone":102,"email":103},[111],{"name":112,"affiliation":12,"role":113},"Joseph Houmard, PhD","PRINCIPAL_INVESTIGATOR",[115,119,122,125,128],{"pmid":116,"type":117,"citation":118},"24951618","BACKGROUND","Ryan TE, Brophy P, Lin CT, Hickner RC, Neufer PD. Assessment of in vivo skeletal muscle mitochondrial respiratory capacity in humans by near-infrared spectroscopy: a comparison with in situ measurements. J Physiol. 2014 Aug 1;592(15):3231-41. doi: 10.1113\u002Fjphysiol.2014.274456. Epub 2014 Jun 20.",{"pmid":120,"type":117,"citation":121},"30257218","Fisher-Wellman KH, Davidson MT, Narowski TM, Lin CT, Koves TR, Muoio DM. Mitochondrial Diagnostics: A Multiplexed Assay Platform for Comprehensive Assessment of Mitochondrial Energy Fluxes. Cell Rep. 2018 Sep 25;24(13):3593-3606.e10. doi: 10.1016\u002Fj.celrep.2018.08.091.",{"pmid":123,"type":117,"citation":124},"29476613","Chondronikola M, Magkos F, Yoshino J, Okunade AL, Patterson BW, Muehlbauer MJ, Newgard CB, Klein S. Effect of Progressive Weight Loss on Lactate Metabolism: A Randomized Controlled Trial. Obesity (Silver Spring). 2018 Apr;26(4):683-688. doi: 10.1002\u002Foby.22129. Epub 2018 Feb 24.",{"pmid":126,"type":117,"citation":127},"28467922","Goodpaster BH, Sparks LM. Metabolic Flexibility in Health and Disease. Cell Metab. 2017 May 2;25(5):1027-1036. doi: 10.1016\u002Fj.cmet.2017.04.015.",{"pmid":129,"type":117,"citation":130},"18765680","Galgani JE, Moro C, Ravussin E. Metabolic flexibility and insulin resistance. Am J Physiol Endocrinol Metab. 2008 Nov;295(5):E1009-17. doi: 10.1152\u002Fajpendo.90558.2008. Epub 2008 Sep 2.",[],{"nct_id":4,"conditions":133,"biomarkers":134},[18,20],[135],"Lactate",{"nct_id":4,"found":137,"summary":138,"prompt_version":148},true,{"design":139,"status":140,"heading":141,"summary":142,"follow_up":143,"word_count":144,"commitments":145,"compensation":146,"drugs_mentioned":147},"This is an observational study planning to enroll 100 participants. It compares overweight individuals with different lactate levels and severely obese individuals.","completed","Observational Study on Metabolic Inflexibility and Obesity Risk","This observational study is looking at how your body uses energy (metabolism) and its connection to metabolic inflexibility, which might increase the risk of obesity. Researchers believe that some overweight individuals might have a \"metabolic program\" in their muscles that makes them more likely to become obese. They are studying overweight individuals (BMI 25-30 kg\u002Fm2) and severely obese women (BMI >40 kg\u002Fm2) who are undergoing weight loss surgery (sleeve gastrectomy). The study will measure how your body burns carbohydrates and fats, and how your muscles use oxygen and release lactate (a chemical produced when your body breaks down sugar for energy). The goal is to understand if relying more on sugar for energy in your muscles leads to metabolic inflexibility and obesity. This study is currently recruiting participants aged 18 to 50 years old.","Participants will be followed for measurements over 1 to 5 years.",134,"Not specified in the trial record.","Not stated in the trial record.",[31],"v2"]