Clinical Trial: Pharmacodynamics of CNP During Growth Hormone Treatment

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Pharmacodynamics of C-Type Natriuretic Peptide During Growth Hormone Treatment in Children: A Potential Biomarker of Efficacy

Brief Summary:

It is now widespread practice to treat children with short stature with growth hormone. However, how an individual child will respond to growth hormone treatment is unpredictable and highly variable. Some children will not respond to growth hormone treatment at all. Currently, the only way to determine how well growth hormone therapy is working is to wait until they have been treated for six months and to compare the pre-treatment growth velocity with the growth velocity on treatment. It would be helpful to have a blood test that could be done shortly after starting growth hormone that could predict whether how well a child is responding to treatment. Such a blood test would allow endocrinologists to adjust the growth hormone dose (or possibly stop it altogether, if it is not working) long before the six months it currently takes.

C-type natriuretic peptide (CNP) and its partner amino-terminal propeptide of CNP (NTproCNP) are proteins that play a critical role in regulating growth. The investigators have previously shown that blood levels of these proteins increase in children being treated with growth hormone. The investigators believe that a blood test for these proteins will be useful in predicting a child's response to growth hormone treatment.

The purpose of this study is to determine when after starting growth hormone, the blood levels of CNP and NTproCNP start to increase.


Detailed Summary:

Treatment of children with short stature with recombinant human growth hormone is widespread practice. However, the growth response to growth hormone treatment is highly variable, particularly for those children who do not have classic growth hormone deficiency. The availability of a biomarker of efficacy that can be measured early in treatment would be beneficial.

C-type natriuretic peptide (CNP) plays a critical role in linear growth. CNP is produced in the growth plate and signals through a paracrine mechanism. Its bioinactive amino-terminal propeptide (NTproCNP) is easily measurable in plasma and levels reflect rate of CNP biosynthesis. Previous studies in lambs and children have shown that the plasma concentration of NTproCNP correlates with linear growth velocity and the investigators have also shown that levels are increased during growth hormone therapy. The investigators have proposed that NTproCNP is a biomarker for linear growth and consider it the first "growth plate function test." Such a growth biomarker is likely to reflect efficacy of growth hormone therapy soon after starting growth hormone, possibly as soon as a few days. Before the clinical utility of this can be determined, the investigators need to ascertain the pharmacodynamics of CNP and NTproCNP in response to growth hormone.

The goal of this study is to describe the pharmacodynamics of the CNP response to the initiation of growth hormone in two sets of children with short stature, those with growth hormone deficiency and those in whom normal growth hormone secretion (idiopathic short stature) and to compare these data to the pharmacodynamics of other peptides previously identified as potential biomarkers. The investigators hypothesize that plasma NTproCNP levels will increase within four days of starting growth hormone therapy and that th
Sponsor: Nemours Children's Clinic

Current Primary Outcome: Determine the time after starting rhGH that NTproCNP level reaches 95% of its peak level [ Time Frame: One year ]

NTproCNP will be modeled over time for each individual subject and the time it reaches 95% of its peak value determined. This value will then be averaged for the cohort.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Correlate NTproCNP levels at the time it reaches 95% of its peak with six-month and one year growth velocity on rhGH treatment [ Time Frame: one year ]
  • Compare NTproCNP levels with other biomarkers of growth (serum IGF-I, bone-specific alkaline phosphatase, and leptin, and urine deoxypyridinoline) during rhGH treatment [ Time Frame: One year ]


Original Secondary Outcome: Same as current

Information By: Nemours Children's Clinic

Dates:
Date Received: July 20, 2011
Date Started: November 2010
Date Completion:
Last Updated: September 30, 2014
Last Verified: September 2014