The current study is designed to collect viable growth plate tissue of tall statured individuals that undergo percutaneous epiphysiodesis (PE). With this collected biomaterial we will be able to characterize dynamic changes in growth plate…
ID
Source
Brief title
Condition
- Endocrine and glandular disorders NEC
- Tendon, ligament and cartilage disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Can we harvest viable growth plate tissue from patients undergoing routine
percutaneous epiphysiodesis?
2. Can we use these growth plate biopsies to make ex vivo explant cultures,
perform histology, characterize molecular processes from RNA and DNA of
different cell types of the human growth plate?
3. Can we perform functional studies with in vitro and ex vivo cells/explants
to test the effects of current growth-promoting or -inhibiting compounds such
as GH, GH-receptor antagonists and C-natriuretic peptide?
To our knowledge this study would provide the first collection of biospecimen
to systematically study pharmaceutical effects directly at the level of the
human growth plate.
The ultimate goal of this study is to form a multidisciplinary research line
that will develop human growth plate models and apply molecular epidemiology
such as proteomics, metabolomics, and molecular profiling (genome,
transcriptome, and epigenome). This will open the way for novel models to study
determinants of growth plate function and eventually medical therapies in
growth disorders and several paediatric orthopaedic conditions.
Secondary outcome
N/A
Background summary
Human growth plate tissue would be extremely valuable to elucidate underlying
mechanisms of severe short stature and the degenerative joint disease
osteoarthritis (OA). Furthermore in the field of articular cartilage
regeneration a knowledge gap of cell fate decisions towards articular
chondrocytes precludes deposition of high quality neo-cartilage. Studying
dynamic changes in growth plate chondrocyte signalling will provide critical
insight into functional determinants of both growth plate and articular
chondrocytes.
Study objective
The current study is designed to collect viable growth plate tissue of tall
statured individuals that undergo percutaneous epiphysiodesis (PE). With this
collected biomaterial we will be able to characterize dynamic changes in growth
plate chondrocyte signalling during endochondral ossification and maturation
and set up a human ex vivo growth plate model. Such a model could greatly
enhance our ability to study underlying mechanisms of growth-related problems,
osteoarthritis and apply regenerative medicine while providing a tailored human
disease model to test effects of current and novel compounds e.g. GH,
GH-receptor antagonists and C-natriuretic peptides.
The following objectives are formulated:
1. Harvest viable growth plate tissue from paediatric patients undergoing
routine orthopaedic removal of their growth plates.
2. Isolate viable growth plate cells at different stages of maturation.
3. Characterize, at the molecular level, growth plate cells at different stages
of maturation.
4. Set up a human ex vivo explant model of growth plate tissue.
Study design
In this observational study we aim to establish a collection of growth plate
tissues from 100 patients with tall stature undergoing routine PE.
Growth plate tissue will be collected (and not discarded) by the surgeon during
surgery in containers with a study number. Within 4 hours after collection
containers will be transferred to the department of Biomedical Data Sciences,
section Molecular Epidemiology. Here biomaterials will be processed and stored
according to a previously established protocol. The biomaterial will be used to
answer the main study objectives as outlined above. In case future (new)
research questions on the collected material are developed, an amendment to
this protocol, will be submitted to the CME LUMC for approval.
We propose to divide the study into two phases. The first phase will consist of
the sequential inclusion of 10 patients, to test the usefulness and feasibility
of our proposed in vitro research model. If we are able to preserve viable
chondrocytes in the majority of these first 10 patients, we will automatically
proceed to the second phase of the study, which is the sequential inclusion of
approximately 100 patients for further in vitro analysis.
Study burden and risks
Percutaneous epiphysiodesis (PE) is deemed a routine orthopedic procedure with
a low complication rate in general. The risk of post-operative complications as
a result of the study is extremely low as no additional surgical techniques
need to be employed. The caliber of the biopsy needle (8 Gauge) is smaller or
similar to generally used drills and curettes. Orthopedic biopsy has been
proven to be safe in the hands of an experienced orthopedic surgeon. The
trajectory of the biopsy needle is the same as the trajectory used for the
drill in a standard epiphysiodesis
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
Male or female pediatric patients (< 18 years of age) with idiopathic or
familiar tall stature with a predicted adult height > 205 cm (boys) or > 185 cm
(girls), and/or evidence of syndromic condition with predisposition for tall
stature.
Male or female pediatric patients undergoing PE because of idiopathic or
post-traumatic limb length discrepancy or transgender patients (male to female)
who have a predicted adult height in the normal male range but choose to
undergo epiphysiodesis to prevent female tall stature.
Exclusion criteria
General or other standard contra-indications for PE surgery.
Inability to read Dutch and/or verbalize understanding of the study information
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL71533.058.19 |