[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100649789":3},{"organization":4,"outcomesModule":7,"designInfo":64,"detailedDescription":75,"studyPopulation":63,"armGroups":76,"interventions":87,"overallOfficials":97,"centralContacts":101,"locations":111,"responsibleParty":126,"collaborators":63,"id":129,"slug":130,"hasResults":131,"nctId":132,"briefTitle":133,"officialTitle":134,"acronym":135,"eligibilityCriteria":136,"healthyVolunteers":131,"sex":137,"minAge":138,"maxAge":139,"enrollmentInfo":140,"targetDuration":63,"studyType":143,"phases":144,"briefSummary":146,"conditions":147,"keywords":157,"overallStatus":160,"whyStopped":63,"lastUpdateSubmitDate":161,"lastUpdatePostDateStruct":162,"startDateStruct":165,"completionDateStruct":167,"leadSponsor":169,"locationsCount":170},{"fullName":5,"class":6},"Tabriz University of Medical Sciences","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":19,"otherOutcomes":63},[9,13,16],{"measure":10,"description":11,"timeFrame":12},"Serum folate level","Changes in serum folate level pre and post the 3-month intervention period.","3 months",{"measure":14,"description":15,"timeFrame":12},"Serum homocysteine level","Changes in serum homocysteine level pre and post the 3-month intervention period.",{"measure":17,"description":18,"timeFrame":12},"Expression of PPARα and TNFα genes","Changes in expression of PPARα and TNFα genes pre and post the 3-month intervention period.",[20,23,26,29,33,36,39,42,45,48,51,54,57,60],{"measure":21,"description":22,"timeFrame":12},"Liver biochemical parameters (ALT (alanine aminotransferase), AST (aspartate aminotransferase), and GGT (gamma-glutamyl transferase)","Changes in ALT, AST, and GGT pre and post the 3-month intervention period.",{"measure":24,"description":25,"timeFrame":12},"The fibrosis-4 (FIB-4) index","Changes in FIB-4 index pre and post the 3-month intervention period. The Fibrosis-4 (FIB-4) index will be calculated using the following formula: FIB-4 = (Age \\[years\\] × AST \\[U\u002FL\\]) \u002F (Platelet count \\[10⁹\u002FL\\] × √ALT \\[U\u002FL\\]). FIB-4 values \\>1.3, indicate a greater likelihood of liver fibrosis.",{"measure":27,"description":28,"timeFrame":12},"Quality of life using SF-36 (36-Item Short Form Health Survey) questionnaires","Changes in quality-of-life pre and post the 3-month intervention period. Health-related quality of life will be assessed using the validated 36-Item Short Form Health Survey (SF-36). The questionnaire evaluates eight health domains: physical functioning, role limitations due to physical health, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health. Scores for each domain will be transformed to a 0-100 scale according to the standard scoring algorithm, with higher scores indicating better health-related quality of life.",{"measure":30,"description":31,"timeFrame":32},"Lipid profile (triglycerides, total cholesterol, LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol))","Changes in lipid profile (triglycerides, total cholesterol, LDL-C, HDL-C) pre and post the 3-month intervention period.","3 monhs",{"measure":34,"description":35,"timeFrame":12},"Fasting blood glucose","Changes in fasting blood glucose pre and post the 3-month intervention period.",{"measure":37,"description":38,"timeFrame":12},"Fasting serum insulin","Changes in fasting serum insulin pre and post the 3-month intervention period.",{"measure":40,"description":41,"timeFrame":12},"QUICKI (quantitative insulin sensitivity check index)","Changes in QUICKI pre and post the 3-month intervention period. The quantitative insulin sensitivity check index (QUICKI) will be calculated as 1\u002F\\[log(fasting insulin \\[µU\u002FmL\\]) + log(fasting glucose \\[mg\u002FdL\\])\\], higher values indicating greater insulin sensitivity.",{"measure":43,"description":44,"timeFrame":12},"HOMA-IR (homeostatic model assessment of insulin resistance","Changes in HOMA-IR pre and post the 3-month intervention period. Insulin resistance will be assessed using the homeostatic model assessment of insulin resistance (HOMA-IR), calculated as fasting insulin (µU\u002FmL) × fasting glucose (mg\u002FdL) \u002F 405, higher values indicating greater insulin resistance.",{"measure":46,"description":47,"timeFrame":12},"Weight","Changes in weight pre and post the 3-month intervention period.",{"measure":49,"description":50,"timeFrame":12},"Body Mass Index (BMI)","Changes in BMI pre and post the 3-month intervention period. Body mass index (BMI) will be calculated as weight (kg) divided by the square of height (m²) and expressed as kg\u002Fm².",{"measure":52,"description":53,"timeFrame":12},"Waist circumference","Changes in waist circumference pre and post the 3-month intervention period.",{"measure":55,"description":56,"timeFrame":12},"Waist-to-hip ratio (WHR)","Changes in WHR pre and post the 3-month intervention period. Waist-to-hip ratio (WHR) will be calculated by dividing waist circumference by hip circumference.",{"measure":58,"description":59,"timeFrame":12},"Body composition (fat-free mass)","Changes in fat-free mass (%) pre and post the 3-month intervention period. Body composition will be determined using a bioelectrical impedance analyzer.",{"measure":61,"description":62,"timeFrame":12},"Body composition (fat mass)","Changes in fat mass (%) pre and post the 3-month intervention period. Body composition will be determined using a bioelectrical impedance analyzer.",null,{"allocation":65,"interventionModel":66,"interventionModelDescription":63,"primaryPurpose":67,"observationalModel":63,"timePerspective":63,"maskingInfo":68},"RANDOMIZED","PARALLEL","TREATMENT",{"masking":69,"maskingDescription":63,"whoMasked":70},"QUADRUPLE",[71,72,73,74],"PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","OUTCOMES_ASSESSOR","Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly termed non-alcoholic fatty liver disease (NAFLD), is diagnosed via liver biopsy or imaging when steatosis is present in the absence of alcohol intake or other hepatic disorders. As the liver manifestation of metabolic syndrome, it commonly coexists with obesity, diabetes, dyslipidemia, hypertension, and related conditions. Global prevalence of MASLD continues to rise.\n\nEvidence from an earlier systematic review and meta-analysis indicated that MASLD patients had significantly lower serum folate and higher homocysteine concentrations. Folate is an essential water-soluble B vitamin that occurs in multiple chemically related forms. Food folates are mainly reduced and polyglutamated, with 5-MTHF predominating in both the diet and systemic circulation. 5-MTHF does not require reduction by DHFR and can enter the bloodstream directly for use. Reduced folates act as methyl donors in one carbon metabolism, supporting cellular proliferation, homocysteine re-methylation to methionine, nucleic acid synthesis and methylation of DNA, RNA, proteins and phospholipids.\n\nExperimental studies have demonstrated that diet-induced hyperhomocysteinemia promotes hepatic steatosis and liver injury and folate as a key regulator of homocysteine concentration, may exert hepatoprotective effects. Evidence suggests that folate may improve hepatic lipid metabolism by activating peroxisome proliferator-activated receptor alpha (PPARα) signaling and modulate the immune response and reduce inflammatory mediators. Nevertheless, no evidence on the effects of folate on PPARα and TNFα gene expression in MASLD patients exist. Moreover, PPARα gene expression is dysregulated in MASLD and related metabolic conditions; PPARα is highly expressed in the liver, skeletal muscle and brown adipose tissue, stimulates β-oxidation and suppresses fatty-acid synthesis. Although the effect of 5-MTHF supplementation on gene expression of PPARα and TNFα in MASLD patients has not been examined, evidence showed that folate can modulate PPARα and TNFα. As folate has been shown to affect lipid metabolism and inflammation, we hypothesized that 5-MTHF supplementation might regulate PPARα and TNFα expression in MASLD patients. This randomized, double-blind, placebo-controlled clinical trial will therefore be undertaken to determine the effects of 5-MTHF supplementation on serum levels of folate and homocysteine, and gene expression of PPARα and TNFα in MASLD patients.",[77,82],{"label":78,"type":79,"description":63,"interventionNames":80},"Intervention","EXPERIMENTAL",[81],"Dietary Supplement: 5-methyltetrahydrofolate (5-MTHF)",{"label":83,"type":84,"description":63,"interventionNames":85},"Placebo","PLACEBO_COMPARATOR",[86],"Dietary Supplement: placebo group",[88,93],{"type":89,"name":90,"description":91,"armGroupLabels":92,"otherNames":63},"DIETARY_SUPPLEMENT","5-methyltetrahydrofolate (5-MTHF)","Patients in this group will receive 5-methyltetrahydrofolate tablets (800 mcg) once a day for 90 days. Tablets will be manufactured by Ashbal Chemi pharmaceutical company (Qfol, Ashbal Chemi Co., Tehran, Iran).",[78],{"type":89,"name":94,"description":95,"armGroupLabels":96,"otherNames":63},"placebo group","Patients in this group will receive placebo for 90 days. The placebo is corn starch\u002F cellulose and will be consumed once a day. Placebo tablets will be manufactured by Ashbal Chemi Co. (Tehran, Iran).",[83],[98],{"name":99,"affiliation":5,"role":100},"Bahram Pourghassem Gargari","PRINCIPAL_INVESTIGATOR",[102,107],{"name":103,"role":104,"phone":105,"phoneExt":63,"email":106},"Fatemeh Tamjid, MSc, PhD student","CONTACT","+989144755462","tamjid.f@tbzmed.ac.ir",{"name":108,"role":104,"phone":109,"phoneExt":63,"email":110},"Bahram Pourghassem Gargari, PhD. Professor at TUMS","+989143165247","pourghassemb@tbzmed.ac.ir, bahrampg@yahoo.com",[112],{"facility":113,"status":63,"city":114,"state":63,"zip":63,"country":115,"countryCode":116,"cosmosGeoPoint":117,"geoPoint":122,"contacts":123},"Liver Clinic of Valiasr Hospital (Tabriz, Iran)","Tabriz","Iran","IR",{"type":118,"coordinates":119},"Point",[120,121],46.2919,38.08,{"lat":121,"lon":120},[124,125],{"name":103,"role":104,"phone":105,"phoneExt":63,"email":106},{"name":108,"role":104,"phone":109,"phoneExt":63,"email":110},{"type":100,"investigatorFullName":127,"investigatorTitle":128,"investigatorAffiliation":5,"oldNameTitle":63,"oldOrganization":63},"Fatemeh Tamjid","Principal Investigator","100649789","the-effects-of-5-methyltetrahydrofolate-supplementation-in-patients-with-metabolic-dysfunction-associated-steatotic-liver-disease-100649789",false,"NCT07740109","The Effects of 5-methyltetrahydrofolate Supplementation in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease","The Effect of 5-methyltetrahydrofolate Supplementation on Serum Folate and Homocysteine Level and PPARα and TNFα Gene Expression in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: a Double-blind, Parallel Randomized Controlled Trial Study","MASLD","Inclusion Criteria:\n\n* Adult men or women (18-50 years)\n* Diagnosis of MASLD (grade 1 or 2 of steatosis confirmed by ultrasound)\n* Body mass index (BMI) = 25-34.9 kg\u002Fm²\n* Providing written informed consent\n\nExclusion Criteria:\n\n* Pregnancy, lactation, or plans to get pregnant during the next three months.\n* Liver disease (viral hepatitis, autoimmune liver disease, cirrhosis, drug-induced hepatotoxicity, or alcoholic fatty liver disease), heart or renal failure, kidney stones, any neoplasia, inflammatory disease, hypothyroidism, hypercortisolism, or hypertension\n* Taking drugs affecting glucose or lipid metabolism, folate supplements, anti-obesity medications, weight-loss diets, or dietary supplements\n* Lifestyle factors known to impact folate status (current smoking, alcohol intake, recreational drug use)\n* Pre-existing conditions affecting folate status (malabsorptive or inflammatory bowel diseases, active celiac disease, gastric bypass surgery, atrophic gastritis, epilepsy, advanced liver disease, kidney dialysis, type 1 or 2 diabetes mellitus, or sickle cell trait\u002Fanemia)\n* Medications that interfere with B-vitamin metabolism (chloramphenicol, methotrexate, metformin, sulfasalazine, phenobarbital, phenytoin, primidone, triamterene, barbiturates)","ALL","18 Years","50 Years",{"count":141,"type":142},44,"ESTIMATED","INTERVENTIONAL",[145],"NA","To determine the effect of MTHF supplementation on serum folate and homocysteine level, metabolic, nutritional status, liver function, and PPARα and TNFα gene expression in patients with MASLD",[148,149,150,135,151,152,153,154,155,156],"Nonalcoholic Fatty Liver Disease","Nonalcoholic Fatty Liver Disease (NAFLD)","MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease","NAFLD","Metabolic Dysfunction-Associated Steatotic Liver Disease","NAFLD (Nonalcoholic Fatty Liver Disease)","NAFLD (Non-alcoholic Fatty Liver Disease)","NAFLD - Non-Alcoholic Fatty Liver Disease","NAFLD - Nonalcoholic Fatty Liver Disease",[158,159,135,151,148,152],"5-methyltetrahydrofolate","homocysteine","NOT_YET_RECRUITING","2026-07-30",{"date":163,"type":164},"2026-07-31","ACTUAL",{"date":166,"type":142},"2026-09-30",{"date":168,"type":142},"2027-08-30",{"name":5,"class":6},1]