Curcumin for Pediatric Nonalcoholic Fatty Liver Disease

Overview

This is a single-center, randomized, double-blinded, placebo-controlled, parallel treatment groups phase 2a study of curcumin for pediatric nonalcoholic fatty liver disease (NAFLD).

Full Title of Study: “Curcumin for Pediatric Nonalcoholic Fatty Liver Disease: A Pilot Randomized Controlled Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: April 22, 2020

Detailed Description

30 subjects ages 8-17y, with biopsy-proven NASH/NAFLD (≤ 730 days prior to registration and a NAFLD Activity Score (NAS) of ≥3) and serum ALT at screening ≥ 50 IU/L at enrollment. Eligible participants will receive curcumin 500 mg, 1.0 g or placebo for 24 weeks, randomized 1:1:1. The primary outcome of the study will determine whether 24 weeks of curcumin supplementation compared to matching placebo improves measures of nonalcoholic fatty liver disease (NAFLD) as determined by relative improvement in serum ALT from baseline. The hypothesis is that curcumin will significantly decrease ALT relative to placebo in children with NAFLD.

Interventions

  • Drug: phosphatidylcholine-curcumin complex supplement
    • a dietary curcumin supplement given at two different doses
  • Drug: Placebo curcumin capsule
    • matching placebo to active curcumin capsules

Arms, Groups and Cohorts

  • Active Comparator: Curcumin 500mg capsules
    • Dose will be 500mg daily phosphatidylcholine-curcumin complex supplement, orally for 24 weeks
  • Active Comparator: Curcumin 1000mg capsules
    • Dose will be1g daily of phosphatidylcholine-curcumin complex supplement, orally for 24 weeks
  • Placebo Comparator: Placebo curcumin capsules
    • Dose will be matching placebo capsules daily, orally for 24 weeks

Clinical Trial Outcome Measures

Primary Measures

  • Change in serum alanine aminotransferase (ALT) from baseline.
    • Time Frame: 24 weeks
    • ALT value in U/L

Secondary Measures

  • Relative change in ALT compared to baseline ALT
    • Time Frame: 24 weeks
    • ALT value in U/L
  • Proportion of patients achieving normalization of ALT
    • Time Frame: 24 weeks
    • ALT value in U/L
  • Change in serum aspartate aminotransferase (AST)
    • Time Frame: 24 weeks
    • AST value in U/L
  • Change in serum gamma-glutamyl transpeptidase (GGT)
    • Time Frame: 24 weeks
    • GGT value in U/L
  • Change in ALT at 12 weeks compared to baseline ALT
    • Time Frame: 12 weeks
    • ALT value in U/L
  • Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) compared to baseline
    • Time Frame: 24 weeks
    • is an equation which indicates the degree of insulin resistance, where higher scores equate to greater insulin resistance. HOMA-IR is calculated as fasting (Glucose (mmol/L) x insulin (pmol/L))/22.5. A HOMA-IR value >2.0 in prepubertal children and >2.6 in pubertal children, may be considered a warning sign for pediatricians to further investigate insulin resistance
  • Change in Weight
    • Time Frame: 24 weeks
    • kilograms (kg)
  • Change in Waist circumference
    • Time Frame: 24 weeks
    • centimeters (cm)
  • Change in Waist to Hip ratio
    • Time Frame: 24 weeks
    • ratio of the circumference of the waist to that of the hips. This is calculated as waist measurement divided by hip measurement (W ÷ H).
  • Change in Body-mass Index Z- Score
    • Time Frame: 24 weeks
    • Body mass index z-scores is calculated using age, gender, height and weight and calculated using 2000 CDC Growth Charts for norms.
  • Change in serum lipids compared to baseline
    • Time Frame: 24 weeks
    • lipid profiles
  • Change in High Sensitivity C-Reactive Protein (hsCRP) compared to baseline
    • Time Frame: 24 weeks
    • serum marker of inflammation (mg/L)
  • Change in Pediatric Quality of Life Inventory (PedsQL) Score scores compared to baseline
    • Time Frame: 24 weeks
    • Pediatric Quality of Life Inventory (PedsQL) version 4.0 is completed by both the child and parent/caregiver, and is composed of 23 items comprising 4 dimensions: Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. Scores are transformed on a scale from 0 to 100, with higher scores indicating better health-related quality of life. Physical Health Summary Score =Physical Functioning Scale Score. Psychosocial Health Summary Score = Sum of items over the number of items answered in the Emotional, Social, and School Functioning Scales.
  • Change in Intrahepatic fat content and liver stiffness
    • Time Frame: 24 weeks
    • Hepatic fat content and liver stiffness will be measured by CAP and VCTE (Fibroscan®)
  • Change in frequency of adverse events compared to baseline
    • Time Frame: 24 weeks
    • Numbers of adverse events reported

Participating in This Clinical Trial

Inclusion Criteria

  • Age 8-17 years at initial screening interview – Histological evidence of NAFLD with or without fibrosis and a NAFLD activity score (NAS) of ≥3, on a liver biopsy obtained no more than 730 days prior to enrollment – Serum ALT at screening ≥ 50 IU/L Exclusion Criteria:

  • Significant alcohol consumption or inability to reliably quantify alcohol intake – Use of drugs historically associated with NAFLD (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, other known hepatotoxins) for more than 2 consecutive weeks in the past year prior to randomization – New treatment with vitamin E or metformin started in the past 90 days or plans to alter the dose or stop over the next the 24 weeks. A stable dose is acceptable. – Prior or planned bariatric surgery – Uncontrolled diabetes (HbA1c 9.5% or higher within 30 days prior to enrollment) – Presence of cirrhosis on liver biopsy – Stage 2 Hypertension or >140 systolic or >90 diastolic at screening – Current daily use of nonsteroidal anti-inflammatory drugs (NSAIDs) – Platelet counts below 100,000 /mm3 – Clinical evidence of hepatic decompensation (serum albumin < 3.2 g/dL, international normalized ratio (INR) >1.3, direct bilirubin >1.3 mg/dL, history of esophageal varices, ascites, or hepatic encephalopathy) – Evidence of chronic liver disease other than NAFLD: – Biopsy consistent with histological evidence of autoimmune hepatitis – Serum hepatitis B surface antigen (HBsAg) positive. – Serum hepatitis C antibody (anti-HCV) positive. – Iron/total iron binding capacity (TIBC) ratio (transferrin saturation) > 45% with histological evidence of iron overload – Alpha-1-antitrypsin (A1AT) phenotype/genotype ZZ or SZ – Wilson's disease – History of biliary diversion – History of kidney disease and/or estimated glomerular filtration rate (eGFR) < than 60 mL/min/1.73 m2 using Schwartz Bedside GFR Calculator for Children isotope dilution mass spectroscopy (IDMS)-traceable – Known Human Immunodeficiency Virus (HIV) infection – Active, serious medical disease with life expectancy less than 5 years – Active substance abuse including inhaled or injected drugs, in the year prior to screening – Pregnancy, planned pregnancy, potential for pregnancy and unwillingness to use effective birth control during the trial, breast feeding – Participation in any clinical/investigational trial within the prior 150 days and during the study. – Any other condition which, in the opinion of the investigator, would impede compliance or hinder completion of the study – Inability to swallow capsules – Known allergy to curcumin or any of its components – Failure of parent or legal guardian to give informed consent or subject to give informed assent

Gender Eligibility: All

Minimum Age: 8 Years

Maximum Age: 17 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Columbia University
  • Collaborator
    • Thorne HealthTech, Inc
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Joel E Lavine, MD, PhD, Principal Investigator, Columbia University

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