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Nonalcoholic Fatty Liver Disease (NAFLD)Phase 2/3CyNChNCT01529268

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

A Phase 2/3 study testing DR cysteamine bitartrate capsule in people with Nonalcoholic Fatty Liver Disease (NAFLD), run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 10 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 8 to 17 years
Conditions the study is for
Nonalcoholic Fatty Liver Disease (NAFLD)
What is being tested?
DR cysteamine bitartrate capsule
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
169 participants
Where
10 sitesUnited States
Study dates
Jun 2012to Sep 2015
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 8 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • Emory University

    Atlanta, Georgia, 30322

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

    Chicago, Illinois, 60611-2605

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3039

  • Texas Children's Hospital

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • Columbia University

    New York, New York, 10032

  • University of California, San Diego

    San Diego, California, 92103

  • University of California, San Francisco

    San Francisco, California, 94143

  • University of Washington, Seattle Children's Hospital

    Seattle, Washington, 98105

  • St. Louis University

    St Louis, Missouri, 63104

Other trials in United States

About this study

Official title: Cysteamine Bitartrate Delayed-Release for the Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) in Children (CyNCh)

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.

Being tested
DR cysteamine bitartrate capsule, DR cysteamine bitartrate placebo
Keywords
Nonalcoholic Fatty Liver Disease (NAFLD), Cysteamine bitartrate delayed release, Children
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DR cysteamine bitartrate capsuleDrug

    Also called cysteamine bitartrate delayed-release

    • 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 placeboOther

    • 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
Study groups in NCT01529268
Study groupRoleWhat they receive
DR cysteamine bitartrate capsuleActive comparatorActive DR cysteamine bitartrate capsule
Receives: Drug: DR cysteamine bitartrate capsule
DR cysteamine bitartrate placeboPlacebo comparatorPlacebo DR cysteamine bitartrate capsule
Receives: Other: DR cysteamine bitartrate placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 52 weeks

Secondary outcomes (24)

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

    Change from baseline in the NAFLD Activity Score (NAS), which is a composite score equal to the sum of the steatosis grade (0-3), lobular inflammation grade (0-3), and hepatocellular ballooning grade (0-2), from centralized pathologist scoring of liver biopsies. The overall scale of the NAS is 0-8, with higher scores indicating more severe disease. The outcome measure, change from baseline in NAFLD Activity Score (NAS), has a possible range from -8 to +8, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome. Components of the NAS are scored as follows: Steatosis grade 0=<5% steatosis, 1=5-33% steatosis, 2=34-66% steatosis, 3=>66% steatosis. Lobular inflammation grade=amount of lobular inflammation (combines mononuclear, fat granulomas, and polymorphonuclear (pmn) foci): 0=0, 1=<2 under 20x magnification, 2=2-4 under 20x magnification, 3=>4 under 20x magnification. Hepatocellular ballooning 0=none, 1=mild, 2=more than mild.

    Measured: 52 weeks

  2. Steatosis: Patients With Improvement

    Improvement in steatosis defined as any decrease in steatosis grade comparing 52-week biopsy to baseline.

    Measured: 52 weeks

  3. Steatosis: Change in Score

    Change from baseline in steatosis score. Steatosis score is based on central pathologist grading of liver biopsies: 0=<5% steatosis; 1=5-33% steatosis, 2=34-66% steatosis, 3=>66% steatosis. Change in steatosis score has a possible range of -3 to +3, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome (no improvement).

    Measured: 52 weeks

  4. Lobular Inflammation: Patients With Improvement

    Improvement in lobular inflammation defined as any decrease in lobular inflammation grade comparing 52-week biopsy to baseline.

    Measured: 52 weeks

  5. Lobular Inflammation: Change in Score

    Change from baseline in lobular inflammation score. The amount of lobular inflammation is based on central pathologist grading of liver biopsies, and combines mononuclear, fat granulomas, and polymorphonuclear (pmn) foci: 0=none; 1=<2 under 20x magnification, 2=2-4 under 20x magnification, 3=>4 under 20x magnification. Change in lobular inflammation score has a possible range of -3 to +3, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome (no improvement).

    Measured: 52 weeks

  6. Hepatocellular Ballooning: Patients With Improvement

    Improvement in hepatocellular ballooning defined as any decrease in hepatocellular ballooning score comparing 52-week biopsy to baseline.

    Measured: 52 weeks

  7. Hepatocellular Ballooning: Change in Score

    Change from baseline in hepatocellular ballooning score. The amount of hepatocellular ballooning is based on central pathologist grading of liver biopsies: 0=none; 1=few ballooned hepatocytes, 2=many ballooned hepatocytes. Change in hepatocellular ballooning score has a possible range of -2 to +2, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome (no improvement).

    Measured: 52 weeks

  8. Portal Inflammation: Patients With Improvement

    Improvement in portal inflammation defined as any decrease in portal inflammation score comparing 52-week biopsy to baseline.

    Measured: 52 weeks

  9. Portal Inflammation: Change in Score

    Change from baseline in portal inflammation score. The amount of portal inflammation is based on central pathologist grading of liver biopsies: 0=none; 1=mild, 2=more than mild. Change in portal inflammation score has a possible range of -2 to +2, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome (no improvement).

    Measured: 52 weeks

  10. Fibrosis: Patients With Improvement

    Improvement in fibrosis stage defined as any decrease in fibrosis stage comparing 52-week biopsy to baseline.

    Measured: 52 weeks

  11. Fibrosis: Change in Stage

    Change from baseline in fibrosis stage. The amount of fibrosis is based on central pathologist grading of liver biopsies: 0=none; 1a=mild, zone 3 perisinusoidal, 1b=moderate, zone 3, perisinusoidal, 1c=portal/periportal only, 2=zone 3 and periportal, any combination, 3=bridging, 4=cirrhosis. Fibrosis stages 1a, 1b, 1c recoded as 1, so the possible range of values for fibrosis stage was 0-4. Change in fibrosis stage has a possible range of -4 to +4, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome (no improvement).

    Measured: 52 weeks

  12. Resolution of NASH

    Patients with a change from a histological diagnosis of definite NASH or indeterminate for NASH to not NASH at end of treatment

    Measured: 52 weeks

  13. Change in Serum Aminotransferase and Gamma-glutamyl Transpeptidase

    Measured: 52 weeks

  14. Change in Weight (kg)

    Measured: 52 weeks

  15. Change in Body-mass Index

    Measured: 52 weeks

  16. Change in Body-mass Index Z-score

    Measured: 52 weeks

  17. Change in Waist Circumference

    Measured: 52 weeks

  18. Change in Fasting Serum Glucose

    Measured: 52 weeks

  19. Change in Fasting Insulin

    Measured: 52 weeks

  20. Change in HOMA-IR

    (Glucose (mmol/L) x insulin (pmol/L))/22.5

    Measured: 52 weeks

  21. Change in Systolic Blood Pressure

    Measured: 52 weeks

  22. Change in Diastolic Blood Pressure

    Measured: 52 weeks

  23. Change in Pediatric Quality of Life Inventory (PedsQL) Score

    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.

    Measured: 52 weeks

  24. Reduction in MRI-determined Hepatic Fat Fraction

    Change from baseline in MRI Proton Density Fat Fraction (PDFF) (%).

    Measured: 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2012 (estimated)
  2. Study startJun 2012
  3. Primary completionMar 2015
  4. Study completionSep 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
169 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01529268
Sponsor's protocol ID
NASH-CyNCh
Other IDs
U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730
Acronym
CyNCh
Status last verified
Aug 2017
First submitted
18 Jan 2012
Last updated
10 Jun 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Public use database deposited with the NIDDK Central Repository

Publications

  • Hakim A, Lin KH, Schwantes-An TH, Abreu M, Tan J, Guo X, Yates KP, Lotta L, Verweij N, Loomba R, Kleiner DE, Schwimmer JB, Rotter JI, Chalasani NP. A comprehensive evaluation of candidate genetic polymorphisms in a large histologically characterized MASLD cohort using a novel framework. Hepatol Commun. 2025 May 29;9(6):e0728. doi: 10.1097/HC9.0000000000000728. eCollection 2025 Jun 1.

    PubMed 40434633

  • 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.

    PubMed 38055641

  • 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.

    PubMed 27569726

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing DR cysteamine bitartrate capsule in people with Nonalcoholic Fatty Liver Disease (NAFLD), run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) (time frame: 52 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01529268, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2021.

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