Pharmacodynamics of CNP During Growth Hormone Treatment

September 30, 2014 updated by: Rob Olney, Nemours Children's Clinic

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

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.

Study Overview

Status

Completed

Conditions

Detailed Description

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 the response in children with growth hormone deficiency will be more prompt and greater than those with idiopathic short stature. The investigators second hypothesis is that the increase in NTproCNP in response to growth hormone will correlate with the increase in growth velocity after six and twelve months of treatment.

The study is a prospective observational study of children with growth hormone deficiency (n=10) and with idiopathic short stature (n=10) being started on rhGH therapy. The study consists of frequent monitoring of analyte levels over one year of treatment.

This is a two site study, Nemours Children's Clinic, Jacksonville, Florida and Children's Hospital Los Angeles.

Study Type

Observational

Enrollment (Actual)

22

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Nemours Children Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Children with short stature

Description

Inclusion Criteria:

  • Age greater than 3 years
  • Prepubertal
  • Height SD score less than -2.25
  • Had a growth hormone stimulation test

Exclusion Criteria:

  • History of any other disease or drug treatment that might interfere with linear growth, including amphetamine derivatives for treatment of ADD or ADHD
  • Previous treatment with any growth-promoting medication, including growth hormone
  • Any contraindication to growth hormone therapy
  • Minor acute illness (upper respiratory infections, strep throat, gastroenteritis, urinary tract infection, etc.) less than one month prior to starting growth hormone
  • Major acute illness (pneumonia, meningitis, pyelonephritis, any illness requiring hospitalization, etc.), any surgery, or bone fracture less than six months prior to starting growth hormone
  • Weight less than 13 kg (NCC-J) or 15 kg (CHLA), due to blood volume being drawn.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Growth hormone deficient
Children with short stature, a peak growth hormone response on stimulation testing of less than 7 ng/ml, and no other identifiable cause of short stature
Idiopathic short stature
Children with short stature, a peak growth hormone response on stimulation testing of greater than or equal to 7 ng/ml, and no identifiable cause for the short stature

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
One year

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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
One year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nemours Children's Clinic

Collaborators

Novo Nordisk A/S
Children's Hospital Los Angeles

Investigators

  • Principal Investigator: Robert Olney, MD, Nemours Children's Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2010

Primary Completion (Actual)

March 1, 2013

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

July 20, 2011

First Submitted That Met QC Criteria

January 3, 2012

First Posted (Estimate)

January 5, 2012

Study Record Updates

Last Update Posted (Estimate)

October 2, 2014

Last Update Submitted That Met QC Criteria

September 30, 2014

Last Verified

September 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCC 167624

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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