Clinical trial NCT06152991: Clinical Trial Assessing Godex Carnitine Orotate Complex in Nonalcoholic Fatty Liver Disease Patients for Efficacy
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter, Prospective Comparative, Investigator-initiated Clinical Trial to Evaluate the Efficacy of Carnitine Orotate Complex _Godex® in Patients With Nonalcoholic Fatty Liver Disease
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Non-Alcoholic Fatty Liver Disease
Keywords: NAFLD
Non-Alcoholic Fatty Liver Diease
GODEX
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Celltrion Pharm, Inc.
First posted: 2023-12-01
Enrollment: 196
Sex: ALL
Minimum age (years): 19
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-Blindle
Primary purpose: TREATMENT

Brief summary: the purpose of this clinical trial is to assess the efficacy and safety of Orotic Acid Carnitine Complex Capsules (Godex®) in comparison to a placebo control group in patients with Non-Alcoholic Fatty Liver Disease (NAFLD).

Detailed description: the purpose of this clinical trial is to assess the efficacy and safety of Orotic Acid Carnitine Complex Capsules (Godex®) in comparison to a placebo control group in patients with Non-Alcoholic Fatty Liver Disease (NAFLD).

Godex® is being investigated for its potential to contribute to a reduction in liver fat content and improvement in liver fibrosis when administered over an extended period in patients with NAFLD. Additionally, this study aims to confirm the normalization of HbA1c and ALT, as observed in previous research, and to verify the reduction in intrahepatic fat content through MRI-PDFF analysis and improvement in liver fibrosis via MRE assessment. This investigation is motivated by the insufficient preliminary research on the long-term prescription of Godex® for NAFLD.

Eligibility criteria: Inclusion Criteria:

1. Adults aged 19 to under 75, both male and female.
2. Patients with elevated liver enzymes (AST or ALT ≥ 60 or sustained AST or ALT ≥ 40 to 59 for 3 months or more).
3. For diabetic patients, those with an HbA1c level of less than 8.5% and no changes in the type and dosage of antidiabetic medications in the past 12 weeks.
4. Patients with an MRI-PDFF ≥ 7% indicating evidence of intrahepatic fat deposition, suspected of having non-alcoholic fatty liver disease.
5. Patients who voluntarily consent to participate in this clinical trial and sign the informed consent form.

Exclusion Criteria:

1. Individuals who have experienced a weight fluctuation of over 10% of their prior weight within the past 6 months.
2. Those with AST or ALT levels exceeding 10 times the upper normal limit.
3. Individuals actively involved in dieting or undergoing intense exercise therapy for weight management purposes.
4. Participants with a history of surgical weight loss procedures (e.g., bariatric surgery) or those scheduled for medical or surgical interventions for weight loss during the study period.
5. Individuals with endocrine disorders that may affect body weight (e.g., hypothyroidism, Cushing's syndrome) or those with TSH levels below 0.1uU/ml or above 10.0uU/ml in screening tests.
6. Individuals presenting evidence of chronic hepatitis, including B or C hepatitis (For B or C hepatitis, individuals with positive HBsAg or positive HCV Ab in screening tests and positive HCV RNA are included).
7. Those with a history of alcohol consumption exceeding 210 grams per week for males or 140 grams per week for females within the past year.
8. Individuals who have undergone liver transplantation.
9. Those undergoing renal dialysis or with creatinine levels exceeding twice the upper limit of normal.
10. Individuals in a medically unstable condition to the extent that they cannot participate in the clinical trial based on physical examinations across various organ systems, encompassing cardiovascular, respiratory, gastrointestinal, hepatic-biliary, metabolic, endocrine, renal-urinary, nervous, psychiatric, and other systems.
11. Individuals diagnosed with and treated for malignant tumors within the past 5 years (excluding basal cell carcinoma or squamous cell carcinoma of the skin, provided it has been determined as "cured" after surgery or treatment at the investigator's discretion).
12. Pregnant or lactating women or fertile women who do not consent to using effective contraceptive methods during the study period (oral contraceptives are not considered an effective contraceptive method).
13. Patients currently receiving levodopa.
14. Individuals with genetic conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
15. Individuals with a history of significant alcohol or substance misuse within the past year.
16. hose who have taken medications containing UDCA (Ursodeoxycholic acid), dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethendixoybiphenyl-2,2'-dicarboxylate (DDB), or silymarin components within 4 weeks before the first dose.
17. Those who have taken vitamin E (≥ 800 IU/day), received pioglitazone therapy, or used drugs approved for NASH treatment within 12 weeks before the first dose (exceptions granted if a stable dosage has been maintained for the past 24 weeks).
18. Those who have taken medications affecting body weight within 12 weeks before the first dose, including obesity treatments (absorption inhibitors and appetite suppressants), antidepressants, contraceptives, oral steroids, amphetamines, phentermine, sibutramine, female hormones, thyroid hormones, etc. (exceptions granted if a stable dosage has been maintained for the past 24 weeks).
19. Other individuals deemed unsuitable by the Principal Investigator
20. Those who have taken investigational drugs for other clinical trials within the last 6 months.

Primary outcomes:
measure: Change in intrahepatic fat content measured by MRI-PDFF
timeFrame: 48-week time point compared to baseline.
Secondary outcomes:
measure: Changes in hepatic fibrosis measured by MRE at 96 weeks compared to baseline.
timeFrame: 96-week time point compared to baseline.
measure: Changes in hepatic fat content measured by MRI-PDFF at 96 weeks compared to baseline.
timeFrame: 96-week time point compared to baseline.
measure: Proportion of subjects with a reduction in hepatic fat content measured by MRI-PDFF at 48 and 96 weeks of 20% or more compared to baseline.
timeFrame: 96-week time point compared to baseline.
measure: Proportion of subjects with an improvement in hepatic fibrosis measured by MRE at 96 weeks of 20% or more compared to baseline.
timeFrame: 48-week and 96-week time points compared to baseline.
measure: Changes in CAP measured by Fibroscan at 48 and 96 weeks compared to baseline.
timeFrame: 96-week time point compared to baseline.
measure: Changes in LSM measured by Fibroscan at 48 and 96 weeks compared to baseline.
timeFrame: 96-week time point compared to baseline.
measure: Changes in body weight at 48 and 96 weeks compared to baseline.
timeFrame: 48-week and 96-week time points compared to baseline.
measure: Changes in waist circumference at 48 and 96 weeks compared to baseline.
timeFrame: 48-week and 96-week time points compared to baseline.
measure: Changes in AST, ALT, r-GTP, and normalization rates at 48 and 96 weeks compared to baseline.
timeFrame: 48-week and 96-week time points compared to baseline.
measure: Changes in HOMA-IR ≥2.0 at 48 and 96 weeks compared to baseline
timeFrame: 48-week and 96-week time points compared to baseline.
measure: Changes in glycated hemoglobin (HbA1c) at 48 and 96 weeks compared to baseline
timeFrame: 48-week and 96-week time points compared to baseline.
measure: Changes in fasting blood glucose at 48 and 96 weeks compared to baseline
timeFrame: 48-week and 96-week time points compared to baseline.
measure: Changes in lipid profiles (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides) at 48 and 96 weeks compared to baseline.
timeFrame: 48-week and 96-week time points compared to baseline.
measure: Incidence of NAFLD risk factor diseases (hypertension, diabetes, dyslipidemia, etc.) at 48 and 96 weeks compared to baseline.
timeFrame: 48-week and 96-week time points compared to baseline.
measure: Rate of medication discontinuation due to adverse events.
timeFrame: during the intervention
Other outcomes:
measure: Adverse events
timeFrame: immediately after the intervention
measure: Proportion of subjects with abnormal Laboratory Tests
timeFrame: immediately after the intervention
measure: Proportion of subjects with abnormal vital signs
timeFrame: immediately after the intervention
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: YoonJun Kim, MD.PhD
role: PRINCIPAL_INVESTIGATOR
References: