Curcumin for Pediatric Nonalcoholic Fatty Liver Disease

Columbia University

Status and phase: Withdrawn; Phase 2

Conditions: NAFLD - Nonalcoholic Fatty Liver Disease; NASH - Nonalcoholic Steatohepatitis

Treatments: Drug: phosphatidylcholine-curcumin complex supplement; Drug: Placebo curcumin capsule

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04109742

AAAS6731

Details and patient eligibility

About

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 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.

Sex: All

Ages: 8 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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0 participants in 3 patient groups, including a placebo group

Curcumin 500mg capsules

Active Comparator group

Description:

Dose will be 500mg daily phosphatidylcholine-curcumin complex supplement, orally for 24 weeks

Treatment:

Drug: phosphatidylcholine-curcumin complex supplement

Curcumin 1000mg capsules

Active Comparator group

Description:

Dose will be1g daily of phosphatidylcholine-curcumin complex supplement, orally for 24 weeks

Treatment:

Drug: phosphatidylcholine-curcumin complex supplement

Placebo curcumin capsules

Placebo Comparator group

Description:

Dose will be matching placebo capsules daily, orally for 24 weeks

Treatment:

Drug: Placebo curcumin capsule