Clinical trial NCT04109742: Curcumin for Pediatric Nonalcoholic Fatty Liver Disease
Official title: Curcumin for Pediatric Nonalcoholic Fatty Liver Disease: A Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: NAFLD - Nonalcoholic Fatty Liver Disease
NASH - Nonalcoholic Steatohepatitis
Keywords: Pediatric
NAFLD - nonalcoholic fatty liver disease
Curcumin
Fatty liver
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Thorne HealthTech, Inc
First posted: 2019-09-30
Enrollment: 0
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The comparison of two different doses (500mg/qd and 1g/qd) of a phosphatidylcholine-curcumin complex supplement, to matching placebo
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in serum alanine aminotransferase (ALT) from baseline.
timeFrame: 24 weeks
Secondary outcomes:
measure: Relative change in ALT compared to baseline ALT
timeFrame: 24 weeks
measure: Proportion of patients achieving normalization of ALT
timeFrame: 24 weeks
measure: Change in serum aspartate aminotransferase (AST)
timeFrame: 24 weeks
measure: Change in serum gamma-glutamyl transpeptidase (GGT)
timeFrame: 24 weeks
measure: Change in ALT at 12 weeks compared to baseline ALT
timeFrame: 12 weeks
measure: Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) compared to baseline
timeFrame: 24 weeks
measure: Change in Weight
timeFrame: 24 weeks
measure: Change in Waist circumference
timeFrame: 24 weeks
measure: Change in Waist to Hip ratio
timeFrame: 24 weeks
measure: Change in Body-mass Index Z- Score
timeFrame: 24 weeks
measure: Change in serum lipids compared to baseline
timeFrame: 24 weeks
measure: Change in High Sensitivity C-Reactive Protein (hsCRP) compared to baseline
timeFrame: 24 weeks
measure: Change in Pediatric Quality of Life Inventory (PedsQL) Score scores compared to baseline
timeFrame: 24 weeks
measure: Change in Intrahepatic fat content and liver stiffness
timeFrame: 24 weeks
measure: Change in frequency of adverse events compared to baseline
timeFrame: 24 weeks
Other outcomes:
measure: Plasma concentrations of curcumin and active metabolites from baseline to 24 weeks.
timeFrame: Day 0 pre-dose and 1, 2, 4, 6, 8 hours post-dose; Day 14; Day 28; Day 84 and Day 168
measure: Change in interleukin 6 (IL-6)
timeFrame: 24 weeks
measure: Change in interleukin 8 (IL-8)
timeFrame: 24 weeks
measure: Change in (TNF-a) Tumor Necrosis Factor alpha
timeFrame: 24 weeks
measure: Change in Plasminogen Activator Inhibitor (PAI-1)
timeFrame: 24 weeks
measure: Change in adiponectin
timeFrame: 24 weeks
Locations:
Study officials:
affiliation: Columbia University
name: Joel E Lavine, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: