AchondroplasiaNCT01541306
C-Type Natriuretic Peptide and Achondroplasia
An observational study of Achondroplasia and Hypochondroplasia, run by Nemours Children's Clinic at 1 site in United States.
Trial summary
Achondroplasia and hypochondroplasia are the most common forms of dwarfism. Recent studies have shown that a small hormone called C-type natriuretic peptide (CNP) is an important regulator of linear growth. Read more about this study
- Who is it for?
- Ages 3 months and older
- Conditions the study is for
- Achondroplasia, Hypochondroplasia
- How many people
- 91 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2012to Dec 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 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Children and adults with achondroplasia or hypochondroplasia
Who may be able to join
- a diagnosis of achondroplasia or hypochondroplasia
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Alfred I. duPont Hospital for Children
Wilmington, Delaware, 19803
About this study
Achondroplasia and hypochondroplasia are the most common forms of dwarfism. Recent studies have shown that a small hormone called C-type natriuretic peptide (CNP) is an important regulator of linear growth. The investigators believe that genetic abnormality that causes achondroplasia and hypochondroplasia also disrupts CNP signaling, which may contribute to the growth problem. The investigators propose to look at levels of this and other closely related hormones in children and adults with achondroplasia or hypochondroplasia to see if they are different from levels in healthy people. The investigators hypothesis is that CNP levels are elevated in children with achondroplasia or hypochondroplasia, compared the healthy population. Another hypothesis is that CNP levels are not elevated in adults with achondroplasia or hypochondroplasia, since adults have no growth-plate cartilage. By studying the potential role of the CNP system in achondroplasia and hypochondroplasia, not only will the investigators provide further insight into the pathophysiology of these common syndromes, the investigators will also provide greater insight into the regulation of normal linear growth.
Read the detailed description
Achondroplasia is the most common form of dwarfism and is characterized by short limbs with the thighs and upper arms being the most affected. Achondroplasia is also associated with a narrowing of the foramen magnum and spinal stenosis. Hypochondroplasia is a related, but less severe form of dwarfism that does not have the neurologic problems. Achondroplasia and hypochondroplasia are caused by mutations in the fibroblast growth factor receptor-3 (FGFR-3) gene that causes constitutive activation of the receptor. FGFR-3 signals primarily through the MAP kinase pathway, which is overactivated in growth plate chondrocytes in achondroplasia. C-type natriuretic peptide (CNP) is a hormone that is produced and acts in the growth plate as a potent positive regulator of linear growth. CNP signals through natriuretic peptide receptor-B (NPR-B), generating cGMP. Studies in mice show that activation of the MAP kinase pathway inhibits signaling through NPR-B. Hence the achondroplasia phenotype may be due in part to inhibition of CNP signaling. Conversely, CNP intracellular signaling inhibits the MAP kinase pathway and CNP analogs are being studied as a potential specific therapy for achondroplasia. The objective of this project is to define the state of the CNP system in children and adults with achondroplasia or hypochondroplasia. Our hypotheses are 1) blood levels of CNP and its aminoterminal propeptide (NTproCNP) are elevated and blood levels of cGMP are reduced in children with achondroplasia or hypochondroplasia, due to inhibition of NPR-B; 2) CNP and NTproCNP levels are normal in adults with achondroplasia and hypochondroplasia, due to their lack of growth plate cartilage; and 3) as in healthy children, NTproCNP levels predict height velocity in children with achondroplasia or hypochondroplasia. These hypotheses will be addressed with two specific aims. Specific aim 1 is to determine plasma levels of CNP, NTproCNP, and cGMP in children and adults with achondroplasia or hypochondroplasia. Specific aim 2 is to determine if NTproCNP levels correlate with height velocity in children with achondroplasia or hypochondroplasia.
The study is an observational, cross-sectional/partially longitudinal study of children and adults with achondroplasia or hypochondroplasia. Children will be seen as part of routine clinic visits. Children seen more than once during the study period will provide longitudinal data. Adult subjects with achondroplasia or hypochondroplasia will be studied a single time. Data collected will include anthropometrics, information on neurologic complications of achondroplasia, and blood levels of CNP, NTproCNP, and cGMP. We anticipate 100 subjects will be recruited, with about 20 being studied as many as three times during the course of the study.
By studying the potential role of the CNP system in achondroplasia and hypochondroplasia, not only will we provide further insight into the pathophysiology of these common syndromes, we will also provide greater insight into the regulation of normal linear growth.
- Conditions
- Achondroplasia, Hypochondroplasia
- Keywords
- C-type natriuretic peptide, dwarfism, growth, achondroplasia, hypochondroplasia, biomarker
- Medical subject headings
- Achondroplasia, Hypochondroplasia, Dwarfism
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 |
|---|---|---|
| achondroplasia or hypochondroplasia | Children or adults with achondroplasia or hypochondroplasia |
What is being measured
The primary outcome is the main question the study is designed to answer.
NTproCNP level in plasma
Aminoterminal propeptide of CNP (NTproCNP) is measured in plasma by RIA and compared to an existing sex- and age- based reference range.
Measured: one time point
Secondary outcomes (3)
CNP level in plasma
C-type natriuretic peptide is measured in plasma by RIA and compared to an existing sex- and age- based reference range.
Measured: one time point
cGMP level in plasma
Cyclic GMP levels are measured in plasma by RIA and compared to existing age- and sex- matched control samples.
Measured: one time point
Correlation between NTproCNP level and height velocity in children
NTproCNP levels at baseline will be correlated with hieght velocity determined at subsequent visits. Measurements for determination of height velocity will be at least 6 months apart, but no more than 2 years apart. For subjects with multiple subsequent visits, the visit closest to 1 year after the baseline visit will be used for height velocity determination.
Measured: Every six months over a period of a minumum of six months to a maximum of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2012 (estimated)
- Study startFeb 2012
- Primary completionDec 2013
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AchondroplasiaStudies 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nemours Children's Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Alfred I. duPont Hospital for Children, University of Otago
- Responsible party
- Principal investigator, Rob Olney, Nemours Children's Clinic
- Investigators
- Robert Olney, MD, Principal investigator, Nemours Children's ClinicMichael Bober, MD, PhD, Principal investigator, Alfred I. duPont Hospital for Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01541306
- Sponsor's protocol ID
- Nemours FL IRB 302926
- Status last verified
- Apr 2015
- First submitted
- 13 Feb 2012
- Last updated
- 14 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Olney RC, Prickett TC, Espiner EA, Mackenzie WG, Duker AL, Ditro C, Zabel B, Hasegawa T, Kitoh H, Aylsworth AS, Bober MB. C-type natriuretic peptide plasma levels are elevated in subjects with achondroplasia, hypochondroplasia, and thanatophoric dysplasia. J Clin Endocrinol Metab. 2015 Feb;100(2):E355-9. doi: 10.1210/jc.2014-2814. Epub 2014 Nov 11.
PubMed 25387261
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- C-Type Natriuretic Peptide and Achondroplasia
- ClinicalTrials.gov ID
- NCT01541306
- Acronym / sponsor ID
- Nemours FL IRB 302926
- Conditions
- Achondroplasia, Hypochondroplasia
- Keywords
- C-type natriuretic peptide, dwarfism, growth, achondroplasia, hypochondroplasia, biomarker
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- Nemours Children's ClinicUniversity, hospital or other
- Collaborators
- Alfred I. duPont Hospital for Children, University of Otago
- Study start
- Feb 2012
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 29 Feb 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.
Achondroplasia and hypochondroplasia are the most common forms of dwarfism. Recent studies have shown that a small hormone called C-type natriuretic peptide (CNP) is an important regulator of linear growth. The investigators believe that genetic abnormality that causes achondroplasia and hypochondroplasia also disrupts CNP signaling, which may contribute to the growth problem. The investigators propose to look at levels of this and other closely related hormones in children and adults with achondroplasia or hypochondroplasia to see if they are different from levels in healthy people. The investigators hypothesis is that CNP levels are elevated in children with achondroplasia or hypochondroplasia, compared the healthy population. Another hypothesis is that CNP levels are not elevated in adults with achondroplasia or hypochondroplasia, since adults have no growth-plate cartilage. By studying the potential role of the CNP system in achondroplasia and hypochondroplasia, not only will the investigators provide further insight into the pathophysiology of these common syndromes, the investigators will also provide greater insight into the regulation of normal linear growth.
Detailed description
Achondroplasia is the most common form of dwarfism and is characterized by short limbs with the thighs and upper arms being the most affected. Achondroplasia is also associated with a narrowing of the foramen magnum and spinal stenosis. Hypochondroplasia is a related, but less severe form of dwarfism that does not have the neurologic problems. Achondroplasia and hypochondroplasia are caused by mutations in the fibroblast growth factor receptor-3 (FGFR-3) gene that causes constitutive activation of the receptor. FGFR-3 signals primarily through the MAP kinase pathway, which is overactivated in growth plate chondrocytes in achondroplasia. C-type natriuretic peptide (CNP) is a hormone that is produced and acts in the growth plate as a potent positive regulator of linear growth. CNP signals through natriuretic peptide receptor-B (NPR-B), generating cGMP. Studies in mice show that activation of the MAP kinase pathway inhibits signaling through NPR-B. Hence the achondroplasia phenotype may be due in part to inhibition of CNP signaling. Conversely, CNP intracellular signaling inhibits the MAP kinase pathway and CNP analogs are being studied as a potential specific therapy for achondroplasia. The objective of this project is to define the state of the CNP system in children and adults with achondroplasia or hypochondroplasia. Our hypotheses are 1) blood levels of CNP and its aminoterminal propeptide (NTproCNP) are elevated and blood levels of cGMP are reduced in children with achondroplasia or hypochondroplasia, due to inhibition of NPR-B; 2) CNP and NTproCNP levels are normal in adults with achondroplasia and hypochondroplasia, due to their lack of growth plate cartilage; and 3) as in healthy children, NTproCNP levels predict height velocity in children with achondroplasia or hypochondroplasia. These hypotheses will be addressed with two specific aims. Specific aim 1 is to determine plasma levels of CNP, NTproCNP, and cGMP in children and adults with achondroplasia or hypochondroplasia. Specific aim 2 is to determine if NTproCNP levels correlate with height velocity in children with achondroplasia or hypochondroplasia.
The study is an observational, cross-sectional/partially longitudinal study of children and adults with achondroplasia or hypochondroplasia. Children will be seen as part of routine clinic visits. Children seen more than once during the study period will provide longitudinal data. Adult subjects with achondroplasia or hypochondroplasia will be studied a single time. Data collected will include anthropometrics, information on neurologic complications of achondroplasia, and blood levels of CNP, NTproCNP, and cGMP. We anticipate 100 subjects will be recruited, with about 20 being studied as many as three times during the course of the study.
By studying the potential role of the CNP system in achondroplasia and hypochondroplasia, not only will we provide further insight into the pathophysiology of these common syndromes, we will also provide greater insight into the regulation of normal linear growth.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| achondroplasia or hypochondroplasia | – | –Children or adults with achondroplasia or hypochondroplasia |
Who may qualify
- Ages
- 3 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Children and adults with achondroplasia or hypochondroplasia
Key inclusion criteria (1 listed)
- a diagnosis of achondroplasia or hypochondroplasia
Key exclusion criteria (0 listed)
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
NTproCNP level in plasma
Time frame: one time point
Aminoterminal propeptide of CNP (NTproCNP) is measured in plasma by RIA and compared to an existing sex- and age- based reference range.
3 secondary outcomes
CNP level in plasma
Time frame: one time point
cGMP level in plasma
Time frame: one time point
Correlation between NTproCNP level and height velocity in children
Time frame: Every six months over a period of a minumum of six months to a maximum of 2 years
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 14 Apr 2015.
- Derived from this study: PubMed 25387261Olney RC, Prickett TC, Espiner EA, Mackenzie WG, Duker AL, Ditro C, Zabel B, Hasegawa T, Kitoh H, Aylsworth AS, Bober MB. C-type natriuretic peptide plasma levels are elevated in subjects with achondroplasia, hypochondroplasia, and thanatophoric dysplasia. J Clin Endocrinol Metab. 2015 Feb;100(2):E355-9. doi: 10.1210/jc.2014-2814. Epub 2014 Nov 11.
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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
Michael Bober, MD, PhD principal investigator
Alfred I. duPont Hospital for Children
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Achondroplasia and Hypochondroplasia, run by Nemours Children's Clinic at 1 site 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 1 inclusion and 0 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 14 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
NTproCNP level in plasma (time frame: one time point). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01541306, which also lists 1 linked publication.
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 14 Apr 2015.