Clinical trial NCT02611089: Muscle Connective Tissue in Limb Development and Disease
Official title: Muscle Connective Tissue in Limb Development and Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Radial Dysplasia
Keywords: Muscle connective tissue
Small leucine-rich proteoglycans
Limb development
Lead sponsor: King's College London
Sponsor class: OTHER
Collaborators: name: Great Ormond Street Hospital for Children NHS Foundation Trust
name: Royal Free Hospital NHS Foundation Trust
name: Chelsea and Westminster NHS Foundation Trust
First posted: 2015-11-20
Enrollment: 45
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cases - Any patient attending Great Ormond Street Hospital for reconstructive hand surgery for radial dysplasia.

Controls - Any patient attending Oxford University Hospitals, Chelsea and Westminster or the Royal Free Hospital for reconstructive hand surgery.

Brief summary: The objective of this work is to understand how the disruption of the muscle connective tissue contributes to the limb soft-tissue defects in radial dysplasia. In parallel, the researchers will investigate the role of muscle connective tissue in normal limb development.

Detailed description: The objective of this work is to understand the origins of the soft tissue defects in a disabling, disfiguring limb anomaly called radial dysplasia, and what mechanisms of normal limb development have been disrupted in these patients to produce their phenotype. The investigators aim to use this knowledge to improve their treatment. Currently, despite sophisticated surgical treatment, the limb malformation the child is born with typically recurs as they grow: it is thus an 'unsolved problem'.

The investigators have previously shown, in an experimental mouse model of radial dysplasia, the underlying soft tissue problem is a change in the muscle connective tissue and its derivatives, causing abnormal soft-tissue patterning. The investigators wish to expand this work into the investigators' patient population by comparing samples of post-natal muscle connective tissue derivatives from radial dysplasia patients with control samples.

The investigators will ask patients undergoing corrective hand surgery to let the investigators take small tissue samples during their planned operations. The investigators will also ask patients having other forms of hand surgery, such as surgery for hand injuries, to let the investigators take similar samples for comparison. In either case, their scar and peri-operative treatment will be unchanged. The investigators will examine the tissue samples in the investigators' laboratory to look for changes in tissue architecture, cellular composition, cell signalling, and how they behave when grown in culture. The investigators will also make attempts to derive cell lines from biopsy samples to use in further studies, exploring cellular phenotype and functional capacity.

Simultaneously, the investigators will look at the long-term surgical outcomes and the range of genetic changes in the investigators' patient population. Eligible patients will be referred for consideration in the (separate) 100,000 genome project; this should further expand the investigators' knowledge of the genetic changes underlying limb anomalies. The ability to combine data on genotype, long-term phenotype and soft tissue changes will give a comprehensive overview of the condition. The investigators expect this to lead to a better understanding of patient subgroups, and to provide a rational basis for improved treatment approaches.

Eligibility criteria: Cases

Inclusion Criteria:

* Patients with a clinical diagnosis of radial dysplasia, requiring reconstructive surgery
* Either sex
* Informed (parental) consent to participate

Exclusion Criteria:

* Patients with a clinical diagnosis of radial dysplasia, but not requiring reconstructive surgery
* Patients with a diagnosis other than radial dysplasia
* Patients with extensive previous scarring to their forearm and hand.
* Patients with a significant pathological skin or soft tissue lesion at the donor site.

Controls

Inclusion Criteria:

* Patients with an injury requiring reconstructive surgery
* Either sex
* Informed (parental) consent to participate

Exclusion Criteria:

* Patients with extensive previous scarring to their forearm and hand.
* Patients with a significant pathological skin or soft tissue lesion at the donor site.

Primary outcomes:
measure: Characterisation of muscle connective tissue derivatives - structure
timeFrame: 3 years
measure: Characterisation of muscle connective tissue derivatives - function
timeFrame: 3 years
Secondary outcomes:
measure: Identification of biomarker(s).
timeFrame: 3 years
measure: Identification of muscle connective tissue progenitor-cell pool.
timeFrame: 3 years
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals
state: Oxfordshire
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Foundation Trust
Study officials:
affiliation: King's College London
name: Malcolm Logan, PhD
role: STUDY_CHAIR
affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust
name: Bran Sivakumar, FRCS(Plast)
role: PRINCIPAL_INVESTIGATOR
affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust
name: Gill Smith, FRCS(Plast)
role: PRINCIPAL_INVESTIGATOR
affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust
name: George Murphy, MA, MRCS
role: PRINCIPAL_INVESTIGATOR
affiliation: Oxford University Hospitals
name: Lucy Cogswell, MA, BMBCh, FRCS Plast
role: PRINCIPAL_INVESTIGATOR
References: