Pituitary DwarfismNCT01504802
Pharmacodynamics of CNP During Growth Hormone Treatment
An observational study of Pituitary Dwarfism and Idiopathic Short Stature, run by Nemours Children's Clinic at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Pituitary Dwarfism, Idiopathic Short Stature
- How many people
- 22 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2010to Sep 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Children with short stature
Who may be able to join
- Age greater than 3 years
- Prepubertal
- Height SD score less than -2.25
- Had a growth hormone stimulation test
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Nemours Children Clinic
Jacksonville, Florida, 32207
Children's Hospital Los Angeles
Los Angeles, California, 90027
About this study
Official title: 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.
Read the 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.
- Conditions
- Pituitary Dwarfism, Idiopathic Short Stature
- Keywords
- Growth hormone, C-type natriuretic peptide, amino-terminal propeptide of C-type natriuretic peptide, insulin-like growth factor-I, bone specific alkaline phosphatase, leptin, deoxypyridinoline, growth velocity, pharmacodynamic, biomarker
- Medical subject headings
- Dwarfism, Pituitary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
Determine the time after starting rhGH that NTproCNP level reaches 95% of its peak level
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.
Measured: One year
Secondary outcomes (2)
Correlate NTproCNP levels at the time it reaches 95% of its peak with six-month and one year growth velocity on rhGH treatment
Measured: 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
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2012 (estimated)
- Study startNov 2010
- Primary completionMar 2013
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pituitary DwarfismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nemours Children's Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital Los Angeles, Novo Nordisk A/S
- Responsible party
- Principal investigator, Rob Olney, Nemours Children's Clinic
- Investigators
- Robert Olney, MD, Principal investigator, Nemours Children's Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01504802
- Sponsor's protocol ID
- NCC 167624
- Status last verified
- Sep 2014
- First submitted
- 20 Jul 2011
- Last updated
- 2 Oct 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacodynamics of C-Type Natriuretic Peptide During Growth Hormone Treatment in Children: A Potential Biomarker of Efficacy
- ClinicalTrials.gov ID
- NCT01504802
- Acronym / sponsor ID
- NCC 167624
- Conditions
- Pituitary Dwarfism, Idiopathic Short Stature
- Keywords
- Growth hormone, C-type natriuretic peptide, amino-terminal propeptide of C-type natriuretic peptide, insulin-like growth factor-I, bone specific alkaline phosphatase, leptin, deoxypyridinoline, growth velocity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Nemours Children's ClinicUniversity, hospital or other
- Collaborators
- Children's Hospital Los Angeles, Novo Nordisk A/S
- Study start
- Nov 2010
- Primary completion
- Mar 2013 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 5 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Children with short stature
Key inclusion criteria (4 listed)
- Age greater than 3 years
- Prepubertal
- Height SD score less than -2.25
- Had a growth hormone stimulation test
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
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.
2 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2014.
- Nemours Children's ClinicLink provided by the sponsor.
- Childrens Hospital Los AngelesLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Olney, MD principal investigator
Nemours Children's Clinic
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pituitary Dwarfism and Idiopathic Short Stature, run by Nemours Children's Clinic at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the time after starting rhGH that NTproCNP level reaches 95% of its peak level (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2014.