Cysteamine Bitartrate Delayed-Release for the Treatment of NAFLD in Children (CyNCh)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT01529268
First received: January 18, 2012
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

CyNCh is a multi-center, placebo-controlled clinical trial of children ages 8 to 17 years with biopsy-confirmed moderate to severe nonalcoholic fatty liver disease (NAFLD). The primary objective is to evaluate whether 52 weeks of treatment with cysteamine bitartrate delayed-release capsules will result in improvement in liver disease severity.


Condition Intervention Phase
Nonalcoholic Fatty Liver Disease (NAFLD)
Drug: DR cysteamine bitartrate capsule
Other: DR cysteamine bitartrate placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Cysteamine Bitartrate Delayed-Release for the Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) in Children (CyNCh)

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Improvement in NAFLD [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Centrally scored and masked assessment of histologic improvement in NAFLD between the baseline liver biopsy and follow-up biopsy after 52 weeks of treatment, where improvement is defined as: (1) decrease in NAS of 2 or more and (2) no worsening of fibrosis.


Secondary Outcome Measures:
  • Reduction in serum aminotransferase and gamma-glutamyl transpeptidase [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Reduction in MRI-determined hepatic fat fraction [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Changes to markers of oxidation and anti-oxidant status: malondialdehyde, F2alpha-isoprostane, total antioxidant capacity, oxidized LDL [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Changes in fasting insulin and glucose [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Changes in weight, height, BMI, and waist circumference [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Changes in the Pediatric Quality of Life score [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Changes to any symptoms the patient may have experienced [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Proportion with a change from a histological diagnosis of definite NASH or indeterminate for NASH to not NASH at end of treatment [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Individual histological characteristics at end of treatment compared to baseline such as steatosis, lobular inflammation, portal chronic inflammation, ballooning, fibrosis score and stage 1a vs 1b fibrosis [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change in mean NAFLD Activity Score (NAS) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: June 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: DR cysteamine bitartrate capsule
Active DR cysteamine bitartrate capsule
Drug: DR cysteamine bitartrate capsule
  • 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline
  • 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline
  • 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
Other Name: cysteamine bitartrate delayed-release
Placebo Comparator: DR cysteamine bitartrate placebo
Placebo DR cysteamine bitartrate capsule
Other: DR cysteamine bitartrate placebo
  • 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline
  • 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline
  • 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

  Eligibility

Ages Eligible for Study:   8 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Children age 8-17 years
  • Liver biopsy obtained within 90 days of screening visit and not more than 120 days before randomization
  • Clinical history consistent with NAFLD
  • Definite NAFLD based upon liver histology
  • No evidence of any other liver disease by clinical history or histological evaluation
  • A histological severity of: NAFLD Activity Score (NAS) ≥ 4.
  • Sexually active female participants of childbearing potential (i.e., not surgically sterile [defined as tubal ligation, hysterectomy, or bilateral oophorectomy]) must agree to utilize the same two acceptable forms of contraception from screening through completion of the study and to complete a serum pregnancy test at each study visit. The acceptable forms of contraception for this study include hormonal contraceptives (oral, implant, transdermal patch, or injection) at a stable dose for at least 3 months prior to screening, and barrier (condom with spermicide, diaphragm with spermicide). Sexual activity will be ascertained at each study visit for post-menarchal females and if sexually active, subject must verify use of the same 2 acceptable forms of contraception. For pre-pubescent children, a documented attestation of abstinence from their parent or guardian will be acceptable.
  • Participants must be able to swallow DR Cysteamine tablets with the tablet intact
  • Written informed consent from parent or legal guardian
  • Written informed assent from the child

Exclusion Criteria:

  • There will be no exclusion criteria based on race, ethnicity or gender.
  • Participants with a current history of the following conditions or any other health issues that make it unsafe for them to participate in the opinion of the Investigators:

    • Inflammatory bowel disease (if currently active) or prior resection of small intestine
    • Heart disease (e.g., myocardial infarction, heart failure, unstable arrhythmias)
    • Seizure disorder
    • Active coagulopathy
    • Gastrointestinal ulcers/bleeding
    • Renal dysfunction with a creatinine clearance < 90 mL/min/m2
    • History of active malignant disease requiring chemotherapy within the past 12 months prior to randomization
    • History of significant alcohol intake (AUDIT questionnaire) or inability to quantify alcohol consumption
    • Chronic use (more than 2 consecutive weeks) of medications known to cause hepatic steatosis or steatohepatitis (systemic glucocorticoids, tetracycline, anabolic steroids, valproic acid, salicylates, tamoxifen) in the past year.
    • The use of other known hepatotoxins within 90 days of liver biopsy or within 120 days of randomization
    • Initiation of medications with the intent to treat NAFLD/NASH in the time period following liver biopsy and prior to randomization
    • History of total parenteral nutrition (TPN) use in year prior to screening
    • History of bariatric surgery or planning to undergo bariatric surgery during study duration
    • Clinically significant depression (patients hospitalized for suicidal ideations or suicide attempts within the past 12 months)
    • Any female nursing, planning a pregnancy, known or suspected to be pregnant, or who has a positive serum pregnancy screen.
  • Non-compensated liver disease with any one of the following hematologic, biochemical, and serological criteria on entry into protocol:

    • Hemoglobin < 10 g/dL;
    • White blood cell (WBC) < 3,500 cells/mm3 of blood;
    • Neutrophil count < 1,500 cells/mm3 of blood;
    • Platelets < 130,000 cells/mm3 of blood;
    • Direct bilirubin > 1.0 mg/dL
    • Total bilirubin >3 mg/dL
    • Albumin < 3.2 g/dL
    • International normalized ratio (INR) > 1.4
  • Poorly controlled diabetes mellitus (hemoglobin A1c (HbA1c) > 9%)
  • Evidence of other chronic liver disease:

    • 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 ZZ or SZ
    • Wilson's disease
  • Children who are currently enrolled in a clinical trial or who received an investigational study drug within 180 days of screening or liver biopsy.
  • Subjects who are not able or willing to comply with the protocol or have any other condition that would impede compliance or hinder completion of the study, in the opinion of the investigator.
  • Failure to give informed consent
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01529268

Locations
United States, California
University of California, San Diego
San Diego, California, United States, 92103
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago (NWU)
Chicago, Illinois, United States, 60611-2605
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Missouri
St. Louis University
St. Louis, Missouri, United States, 63104
United States, New York
Columbia University
New York, New York, United States, 10032
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Washington
University of Washington, Seattle Children's Hospital
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Investigators
Study Director: Edward Doo, MD National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT01529268     History of Changes
Other Study ID Numbers: NASH-CyNCh
Study First Received: January 18, 2012
Last Updated: February 4, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Nonalcoholic Fatty Liver Disease (NAFLD)
Cysteamine bitartrate delayed release
Children

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases
Cysteamine
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014