Increlex Treatment of Children With Chronic Liver Disease and Short Stature

Study Overview
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Brief Summary
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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.

Official Title
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Increlex Treatment of Children With Chronic Liver Disease and Short Stature

Conditions
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Growth Failure, Chronic Liver Disease

Intervention / Treatment
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* Drug: Increlex


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: All patients will be treated with IGF-1 factors<br>Patients will serve as their own control. | Drug: Increlex<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pre-pubertal children, pre-transplant, not treated with growth hormone for at least 3 months