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

NCT01529268 | Completed Phase 2 Results DMC FDA Drug

• 10 other identifiers: NASH-CyNChU01DK061718U01DK061728U01DK061731U01DK061732U01DK061734U01DK061737U01DK061738U01DK061730U01DK061713
• Study Type: interventional
• Target: 169
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Nonalcoholic Fatty Liver Disease (NAFLD)

Keywords

Nonalcoholic Fatty Liver Disease (NAFLD); Cysteamine bitartrate delayed release; Children

Outcome Measures

Primary Outcomes (1)

• Improvement in Nonalcoholic Fatty Liver Disease (NAFLD)

  Centrally scored and masked assessment of histologic improvement in Nonalcholic Fatty Liver Disease (NAFLD) between the baseline liver biopsy and follow-up biopsy after 52 weeks of treatment, where improvement is defined as: (1) decrease in the NAFLD Activity Score (NAS) of 2 or more and (2) no worsening of fibrosis.

  52 weeks

Secondary Outcomes (24)

• Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)

  52 weeks

• Steatosis: Patients With Improvement

  52 weeks

• Steatosis: Change in Score

  52 weeks

• Lobular Inflammation: Patients With Improvement

  52 weeks

• Lobular Inflammation: Change in Score

  52 weeks

Study Arms (2)

DR cysteamine bitartrate capsule

ACTIVE COMPARATOR

Active DR cysteamine bitartrate capsule

Drug: DR cysteamine bitartrate capsule

DR cysteamine bitartrate placebo

PLACEBO COMPARATOR

Placebo DR cysteamine bitartrate capsule

Other: DR cysteamine bitartrate placebo

Interventions

DR cysteamine bitartrate capsule DRUG

* 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

Also known as: cysteamine bitartrate delayed-release

DR cysteamine bitartrate capsule

DR cysteamine bitartrate placebo OTHER

* 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

DR cysteamine bitartrate placebo

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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 nonalcoholic fatty liver disease (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

You may not qualify if:

• 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)

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• National Center for Advancing Translational Sciences (NCATS): collaborator
• National Cancer Institute (NCI): collaborator
• Raptor Pharmaceuticals: collaborator

Study Sites (10)

University of California, San Diego

San Diego, California, 92103, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago (NWU)

Chicago, Illinois, 60611-2605, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

St. Louis University

St Louis, Missouri, 63104, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Washington, Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (2)

• Jain AK, Buchannan P, Yates KP, Belt P, Schwimmer JB, Rosenthal P, Murray KF, Molleston JP, Scheimann A, Xanthakos SA, Behling CA, Hertel P, Nilson J, Neuschwander-Tetri BA, Tonascia J, Vos MB; Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Nutrition assessment and MASH severity in children using the Healthy Eating Index. Hepatol Commun. 2023 Dec 7;7(12):e0320. doi: 10.1097/HC9.0000000000000320. eCollection 2023 Dec 1.

  PMID: 38055641 DERIVED

• Schwimmer JB, Lavine JE, Wilson LA, Neuschwander-Tetri BA, Xanthakos SA, Kohli R, Barlow SE, Vos MB, Karpen SJ, Molleston JP, Whitington PF, Rosenthal P, Jain AK, Murray KF, Brunt EM, Kleiner DE, Van Natta ML, Clark JM, Tonascia J, Doo E; NASH CRN. In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores. Gastroenterology. 2016 Dec;151(6):1141-1154.e9. doi: 10.1053/j.gastro.2016.08.027. Epub 2016 Aug 26.

  PMID: 27569726 DERIVED

Related Links

• Nonalcoholic Steatohepatitis Clinical Research Network Centers
• The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Laura Wilson
• Organization: Johns Hopkins Data Coordinating Center

lwilson9@jhu.edu

410-955-0719

Study Officials

• Edward Doo, MD

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2012
• First Posted: February 8, 2012
• Study Start: June 1, 2012
• Primary Completion: March 1, 2015
• Study Completion: September 1, 2015
• Last Updated: June 10, 2021
• Results First Posted: September 5, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: Currently available
• Access Criteria: Apply through the NIDDK Central Repository: https://www.niddkrepository.org/home/

Locations

US (10)