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Curcumin for Pediatric Nonalcoholic Fatty Liver Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04109742
Recruitment Status : Recruiting
First Posted : September 30, 2019
Last Update Posted : October 9, 2019
Thorne Research Inc.
Information provided by (Responsible Party):
Elena Reynoso, Columbia University

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).

Condition or disease Intervention/treatment Phase
NAFLD - Nonalcoholic Fatty Liver Disease NASH - Nonalcoholic Steatohepatitis Drug: phosphatidylcholine-curcumin complex supplement Drug: Placebo curcumin capsule Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The comparison of two different doses (500mg/qd and 1g/qd) of a phosphatidylcholine-curcumin complex supplement, to matching placebo
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Participants, investigators, clinical staff, and data monitoring committee will not have knowledge of the interventions assigned to individual participants.
Primary Purpose: Treatment
Official Title: Curcumin for Pediatric Nonalcoholic Fatty Liver Disease: A Pilot Randomized Controlled Trial
Estimated Study Start Date : October 14, 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : December 2020

Arm Intervention/treatment
Active Comparator: Curcumin 500mg capsules
Dose will be 500mg daily phosphatidylcholine-curcumin complex supplement, orally for 24 weeks
Drug: phosphatidylcholine-curcumin complex supplement
a dietary curcumin supplement given at two different doses
Other Name: Meriva®

Active Comparator: Curcumin 1000mg capsules
Dose will be1g daily of phosphatidylcholine-curcumin complex supplement, orally for 24 weeks
Drug: phosphatidylcholine-curcumin complex supplement
a dietary curcumin supplement given at two different doses
Other Name: Meriva®

Placebo Comparator: Placebo curcumin capsules
Dose will be matching placebo capsules daily, orally for 24 weeks
Drug: Placebo curcumin capsule
matching placebo to active curcumin capsules

Primary Outcome Measures :
  1. Change in serum alanine aminotransferase (ALT) from baseline. [ Time Frame: 24 weeks ]
    ALT value in U/L

Secondary Outcome Measures :
  1. Relative change in ALT compared to baseline ALT [ Time Frame: 24 weeks ]
    ALT value in U/L

  2. Proportion of patients achieving normalization of ALT [ Time Frame: 24 weeks ]
    ALT value in U/L

  3. Change in serum aspartate aminotransferase (AST) [ Time Frame: 24 weeks ]
    AST value in U/L

  4. Change in serum gamma-glutamyl transpeptidase (GGT) [ Time Frame: 24 weeks ]
    GGT value in U/L

  5. Change in ALT at 12 weeks compared to baseline ALT [ Time Frame: 12 weeks ]
    ALT value in U/L

  6. 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

  7. Change in Weight [ Time Frame: 24 weeks ]
    kilograms (kg)

  8. Change in Waist circumference [ Time Frame: 24 weeks ]
    centimeters (cm)

  9. 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).

  10. 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.

  11. Change in serum lipids compared to baseline [ Time Frame: 24 weeks ]
    lipid profiles

  12. Change in High Sensitivity C-Reactive Protein (hsCRP) compared to baseline [ Time Frame: 24 weeks ]
    serum marker of inflammation (mg/L)

  13. 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.

  14. 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®)

  15. Change in frequency of adverse events compared to baseline [ Time Frame: 24 weeks ]
    Numbers of adverse events reported

Other Outcome Measures:
  1. Plasma concentrations of curcumin and active metabolites from baseline to 24 weeks. [ Time Frame: Day 0 pre-dose and 1, 2, 4, 6, 8 hours post-dose; Day 14; Day 28; Day 84 and Day 168 ]
    Pharmacokinetic analysis

  2. Change in interleukin 6 (IL-6) [ Time Frame: 24 weeks ]
    cytokine protein involved in the pro-inflammatory and anti-inflammatory response

  3. Change in interleukin 8 (IL-8) [ Time Frame: 24 weeks ]
    cytokine protein involved in the pro-inflammatory and anti-inflammatory response

  4. Change in (TNF-a) Tumor Necrosis Factor alpha [ Time Frame: 24 weeks ]
    cytokine protein involved in the pro-inflammatory and anti-inflammatory response

  5. Change in Plasminogen Activator Inhibitor (PAI-1) [ Time Frame: 24 weeks ]
    cytokine protein involved in the pro-inflammatory and anti-inflammatory response

  6. Change in adiponectin [ Time Frame: 24 weeks ]
    cytokine protein involved in the pro-inflammatory and anti-inflammatory response

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   8 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04109742

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Contact: Elena Reynoso, MD, MS 212-305-6274
Contact: Sivan Kinberg, MD

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United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Elena Reynoso, MD, MS    212-305-6274   
Sponsors and Collaborators
Columbia University
Thorne Research Inc.
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Principal Investigator: Joel E Lavine, MD, PhD Columbia University

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Responsible Party: Elena Reynoso, Associate Research Scientist, Columbia University Identifier: NCT04109742    
Other Study ID Numbers: AAAS6731
First Posted: September 30, 2019    Key Record Dates
Last Update Posted: October 9, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Elena Reynoso, Columbia University:
NAFLD - nonalcoholic fatty liver disease
Fatty liver
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action