Increlex Treatment of Children With Chronic Liver Disease and Short Stature

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01314508
Recruitment Status : Withdrawn (The sponsor has notified us that they are not funding the study)
First Posted : March 14, 2011
Last Update Posted : July 14, 2016
Information provided by:
University of California, Los Angeles

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Growth Failure Chronic Liver Disease Drug: Increlex Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Increlex Treatment of Children With Chronic Liver Disease and Short Stature
Study Start Date : June 2011
Actual Primary Completion Date : October 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Mecasermin

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Growth velocity is the primary outcome. Improved height SDS [ Time Frame: One year of therapy ]
    Improved growth velocity with improved height standard deviation scores (SDS) is the primary expected result.

Secondary Outcome Measures :
  1. Improved BMI [ Time Frame: 12 months ]
    An improved body mass index is a secondary expected result of this study.

  2. Improved quality of life [ Time Frame: 12 months ]
    An improved quality of life as assessed by the Pediatric Quality of Life Inventory forms is another expected result.

Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Responsible Party: Anna Haddal, M.D., UCLA Department of Pediatrics, Division of Pediatric Endocrinology Identifier: NCT01314508     History of Changes
Other Study ID Numbers: 07-03-018
First Posted: March 14, 2011    Key Record Dates
Last Update Posted: July 14, 2016
Last Verified: July 2016

Keywords provided by University of California, Los Angeles:
pre-pubertal children
not treated with growth hormone for at least 3 months

Additional relevant MeSH terms:
Liver Diseases
Failure to Thrive
Digestive System Diseases
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Endocrine System Diseases
Signs and Symptoms
Growth Substances
Physiological Effects of Drugs