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

General Description

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, was assessed as the primary outcome measure. Secondary outcome measures, assessed at 52 weeks, included 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 self-reported quality of life.

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.