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

General Description

Nonalcoholic Fatty Liver Disease (NAFLD) spans a range of severity from steatosis, liver disease without injury, to nonalcoholic steatohepatitis (NASH), liver disease which includes fat accumulation, inflammation, and liver injury. In some cases, NASH may progress to cirrhosis, liver failure, and liver cancer. Cysteamine, approved to treat cystinosis, has been shown in a preliminary study to reduce toxins damaging to the liver and improve enzyme activity in children with NASH. The CyNCh (Cysteamine Bitartrate Delayed-Release for the Treatment of NAFLD in Children) study is a prospective, multicenter, double-blind clinical trial designed by the NASH Clinical Research Network to determine whether treatment with cysteamine improves disease severity in children diagnosed with NAFLD.

Children between the ages of 8 and 17 years with biopsy-confirmed moderate to severe NAFLD were eligible for the CyNCh study. Participants were enrolled and randomized to treatment with either delayed-release cysteamine bitartrate capsules or placebo capsules. Improvement in NAFLD at 52 weeks, defined as a decrease in NAFLD Activity Score (NAS) of at least 2 and no worsening of fibrosis, will be assessed as the primary outcome measure. Secondary outcome measures, also to be assessed at 52 weeks, include reduction in serum aminotransferase and gamma-glytamyl transpeptidase, reduction in MRI-determined hepatic fat fraction, changes in markers of oxidation and anti-oxidant status, changes in histology and symptoms, and quality of life.

This study is ongoing.

The current data package includes analysis datasets from the primary outcome publication.

Objectives

The CyNCh trial aims to determine whether treatment with delayed-release cysteamine bitartrate capsules results in improvement in NAFLD severity in children.

Outcome Measure

The primary outcome measure is improvement in NAFLD at 52 weeks, defined as a decrease in NAFLD Activity Score (NAS) of at least 2 and no worsening of fibrosis.

Secondary outcome measures, also to be assessed at 52 weeks, include reduction in serum aminotransferase and gamma-glytamyl transpeptidase, reduction in MRI-determined hepatic fat fraction, changes in markers of oxidation and anti-oxidant status (malondialdehyde, F2alpha-isoprostane, total antioxidant capacity, oxidized LDL), changes in histology and symptoms, and quality of life.

Criteria

Children between the ages of 8 to 17 years who met the following criteria were eligible for enrollment:

• Liver biopsy obtained within 90 days of screening visit and not more than 120 days before randomization
• Clinical history and liver histology consistent with NAFLD
• No evidence of any other liver disease by clinical history or histological evaluation
• A histological severity of NAFLD Activity score ≥ 4

Exclusion criteria are documented in the study protocol.

Outcome

This study is ongoing.