Increlex Treatment of Children With Chronic Liver Disease and Short Stature

A major consequence of chronic liver disease in childhood is growth failure. This is because a chemical essential for growth called growth factor is created in the liver. Lack of response to growth hormone in people with chronic liver disease is characterized by high levels of growth hormone and low levels of growth factors. This growth hormone resistance is reflected in a variety of factors including insulin resistance and low nutritional intake. Unfortunately, growth hormone therapy has no effect for children with liver disease. In addition, failure of normal growth or malnutrition makes liver disease even worse in children, and growth hormone therapy is not likely to reverse this. A lack of proper nutrition is associated with hospitalizations and frequent complications. Poor growth is a predictor of poor outcomes after liver transplantation. Thus the management of children with liver disease remains a challenge. Children who have successful orthotopic liver transplants (OLT) show much improvement in some aspects of growth, including skin fold thickness, mid-arm circumference, and normalization of growth factor levels. However, some studies have recently reported that the growth of 15-20% of children remains poor even after a liver transplant. This can be explained by persistent abnormalities in growth factors after transplant.

Growth factor was found to be a good tool for prognosis in patients with chronic liver disease. Studies showed that patients with liver cirrhosis and growth factor levels below normal values showed lower long-term survival rates compared with patients who had above normal values. This suggests that growth factor can be a good predictor of survival and early marker of poor liver function. In this case, aggressive feeding may modestly improve growth factor levels leading to improved growth but it is unlikely that effects will be optimal. The investigators propose that growth factor administration may have a positive effect that leads to better growth which is a major predictor of good outcome. To date, no reports study the use of growth factor in children with chronic liver disease. This study proposes to examine the effect of growth factor therapy in childhood chronic liver disease.

Study Overview

• Status: Withdrawn
• Conditions: Growth Failure; Chronic Liver Disease
• Intervention / Treatment: Drug: Increlex

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Pre liver transplant patients with:

• Chronic liver disease
• Short stature (< 5%)
• Low IGF-1 (<-1SDS for age)
• Chronologic age 4-18 and bone age < 14 for boys and < 12 for girls (pre-pubertal)

Exclusion Criteria:

• Status post transplant
• Evidence of malignancy
• Diabetes mellitus
• Participation in other clinical trials involving investigational products
• Treatment with growth hormone within 3 months
• Pregnancy
• Significant abnormality in clinical results
• Hypoglycemic at baseline
• Allergic to benzyl alcohol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: All patients will be treated with IGF-1 factors; Patients will serve as their own control.	Drug: Increlex; Increlex therapy will begin at 40 micrograms/kg/day twice a day. The dose will be escalated by 20 mcg twice a day every other week up to 100mcg/kg/week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Growth velocity is the primary outcome. Improved height SDS	Improved growth velocity with improved height standard deviation scores (SDS) is the primary expected result.	One year of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improved BMI	An improved body mass index is a secondary expected result of this study.	12 months
Improved quality of life	An improved quality of life as assessed by the Pediatric Quality of Life Inventory forms is another expected result.	12 months

Collaborators and Investigators

• Sponsor: University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: March 8, 2011
• First Submitted That Met QC Criteria: March 11, 2011
• First Posted (Estimated): March 14, 2011

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: pre-pubertal children; pre-transplant; not treated with growth hormone for at least 3 months
• Additional Relevant MeSH Terms: Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Failure to Thrive; Physiological Effects of Drugs; Growth Substances; mecasermin
• Other Study ID Numbers: 07-03-018