Clinical trial NCT06477146: Milk Thistle Clinical Trial in Pediatric NAFLD
Official title: Pilot Study of Milk Thistle for the Treatment of Pediatric Non-Alcoholic Fatty Liver Disease (NAFLD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-Alcoholic Fatty Liver Disease (NAFLD)
Keywords: Silymarin
Fatty Liver
Lead sponsor: University Hospitals Cleveland Medical Center
Sponsor class: OTHER
First posted: 2024-06-27
Enrollment: 20
Sex: ALL
Minimum age (years): 9
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Pediatric Fatty Liver disease is a growing problem in the United States and is expected to be the leading cause of Liver Transplantation in Adults in 20 years. Following lifestyle changes such as diet restrictions and exercise may be difficult to consistently maintain. The purpose of this study is to investigate alternative medical therapy with an herbal supplement called Milk Thistle (MT) which may improve fatty liver disease and would be easier to follow than diet and exercise.


Eligibility criteria: Inclusion Criteria:

Subjects between the age of 9 to 22 years old diagnosed with non-Alcoholic Fatty Liver Disease (NAFLD) based on current North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Guidelines:

* a. Elevated ALT levels greater than 2 times the sex specific upper limit of normal at baseline; (for boys ALT greater than 50 U/L, and girls ALT greater than 44 U/L) i. AND either overweight (with risk factors as noted below) or obese children:

  * 1. In children, obesity is defined as BMI greater than or equal to 95th percentile in weight and overweight is defined as greater than or equal to the 85th percentile to less than the 95th percentile.
  * 2. Risk factors associated with overweight child that warrant screening and inclusion are:

    a. Central obesity, Family history of NAFLD/non-alcoholic steatohepatitis(NASH), pre-diabetic or diabetic, dyslipidemia, sleep apnea)
  * 3. For participants 18 years or older: Obesity is defined as BMI greater than or equal to 30 kg/m2; overweight is defined as BMI greater than or equal to 25 kg/m2 and less than 30 kg/m2.
* b. Evidence of Sonographic presence of hepatic steatosis with greater than 5% steatosis on Ultrasound or FibroScan \[with a controlled attenuation parameter (CAP) score of 238 or greater)\] prior to start of trial starting.
* c. (Or) previous findings on Liver Biopsy consistent with NAFLD including hepatic macro-vesicular steatosis, ballooning degeneration or Mallory Denk Bodies

Contraception Requirements for Enrollment of adult population:

1. Female participants are eligible if the participant is of reproductive potential and have a negative -serum pregnancy test (beta human chorionic gonadotropin), are not breastfeeding, and do not plan to become pregnant during the study and agree to use two highly effective birth control methods during the study OR if the participant is not of child-bearing potential (i.e., surgically \[bilateral oophorectomy, hysterectomy, or tubal ligation\] or naturally sterile \[\> 12 consecutive months without menses\]).

   Highly effective birth control methods include condoms with spermicide, diaphragm with spermicide, hormonal and nonhormonal intrauterine device, hormonal contraception (estrogens stable ≥ 3 months), a vasectomized male partner, or sexual abstinence (defined as refraining from heterosexual intercourse), from screening, throughout the study, and for at least 30 days after the last dose of study drug administration. Reliance on abstinence from heterosexual intercourse is acceptable only if it is the patient's habitual practice.
2. Male patients who are sexually active with a partner of child-bearing potential must either be sterile (vasectomy with history of a negative sperm count at least 90 days following the procedure); practice total abstinence from sexual intercourse as the preferred lifestyle (periodic abstinence is not acceptable); use a male condom with any sexual activity; or agree to use a birth control method considered to be appropriate by the Investigator (such as one of the methods identified above for female patients of childbearing potential) from the time of screening until 30 days after the last dose of study drug administration. Male patients must agree not to donate sperm for a period of 30 days after the last dose of study drug administration.

Exclusion Criteria:

1. Patients with cardiovascular disorders (such as history of myocardial infarction, stroke, DVT)
2. Medical conditions including history of malignancy, transplantation, immunologic diseases (rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, autoimmune thyroiditis, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, severe psoriasis, rheumatoid arthritis etc.), poorly controlled thyroid disease, uncontrolled hypertension.
3. Patients with cirrhosis and hepatic decompensation will be excluded from the study. Hepatic biomarker parameters will be excluded:

   * ALT greater than 200 U/L
   * AST greater than 200 U/L
   * Total bilirubin greater than 2.0 mg/dL
   * ALP greater than 500 U/L
   * INR greater than 1.4
   * GGT greater than 200 U/L
4. Subjects with history or other evidence of severe illness or any other conditions that would make the subject, in the opinion of the investigator, unsuitable for participation in the trial (such as poorly controlled psychiatric illness).
5. Subjects with unstable diabetes, or HbA1c \>9% will be excluded from the study.
6. Subjects who report binge drinking will be excluded from this study.
7. Subjects who partake or state consumption history of tobacco use, vaping, marijuana use, or illicit drug abuse will be excluded from the study.
8. Subjects with severe hepatic dysfunction and synthetic dysfunction with hypoalbuminemia (Albumin \< 3.0 g/dL), thrombocytopenia (platelet count \<140,000/ml3), or coagulopathy (INR \>1.4) will be excluded from the study.
9. Exclude subjects with abnormal renal function characterized as serum creatinine greater than the upper limit of normal range (based on the University of Iowa, Department of Pathology Lab Services Handbook):

   Pediatric Age Group Premature 0.3 - 1.0 mg/dL Neonates 0.2 - 0.9 mg/dL 2-12 months 0.2 - 0.4 mg/dL 1-2 years 0.2 - 0.5 mg/dL 3-4 years 0.3 - 0.7 mg/dL 5-6 years 0.3 - 0.7 mg/dL 7-8 years 0.2 - 0.6 mg/dL 9-10 years 0.3 - 0.7 mg/dL 11-12 years 0.3 - 0.9 mg/dL 13-15 years 0.4 - 0.9 mg/dL

   Males 16 years and older 0.6 - 1.2 mg/dL Females 16 years and older 0.5 - 1.0 mg/dL
10. Breast feeding women will be excluded from this clinical trial.
11. Subjects who are participating in other drug trials will be excluded from participating.
12. Subjects with a reported or known history of allergy or anaphylactic reaction to Ragweed will be excluded from this study.

Primary outcomes:
measure: Hepatic biomarker alanine aminotransferase (ALT) as measured by blood test.
timeFrame: Up to 12 weeks
measure: Hepatic Stiffness (kilopascal, kPa) as measured by FibroScan.
timeFrame: Up to 12 weeks
measure: Percent of Hepatic Steatosis as measured by FibroScan.
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: Number of adverse events as measured by patient report.
timeFrame: Up to 12 weeks
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
Study officials:
affiliation: University Hospitals
name: Thomas Sferra, MD
role: PRINCIPAL_INVESTIGATOR
References: