Muscle Connective Tissue in Limb Development and Disease

NCT ID: NCT02611089

Last Updated: 2025-08-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

150 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-02-20

Study Completion Date

2036-08-31

Brief Summary

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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

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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.

Conditions

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Radial Dysplasia

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Radial dysplasia patients

Recruited participants will have 2-3 small tissue biopsy samples taken during 1-2 of their planned reconstructive surgical procedures for radial dysplasia, whilst under general anaesthesia in the operating theatre. Samples will be taken by scalpel or scissors, by the operating surgeon, from within the surgical site in the forearm and hand. The skin incision and deep dissection will have to be made as part of the normal course of reconstructive surgery, regardless of participation in this study.

Tissue biopsy

Intervention Type PROCEDURE

Sampling of tissue as described.

Control patients

Recruited participants will have 2-3 small tissue biopsy samples taken during their planned reconstructive surgery for hand trauma, whilst under general anaesthesia in the operating theatre. Samples will be taken by scalpel or scissors, by the operating surgeon, from within the surgical site in the forearm and hand. The skin incision and deep dissection will have to be made as part of the normal course of reconstructive surgery, regardless of participation in this study.

Tissue biopsy

Intervention Type PROCEDURE

Sampling of tissue as described.

Interventions

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Tissue biopsy

Sampling of tissue as described.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

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


* Patients with an injury 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


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

ALL

Accepts Healthy Volunteers

No

Sponsors

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Great Ormond Street Hospital for Children NHS Foundation Trust

OTHER

Sponsor Role collaborator

Royal Free Hospital NHS Foundation Trust

OTHER

Sponsor Role collaborator

Chelsea and Westminster NHS Foundation Trust

OTHER

Sponsor Role collaborator

King's College London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Malcolm Logan, PhD

Role: STUDY_CHAIR

King's College London

Branavan Sivakumar, FRCS(Plast)

Role: PRINCIPAL_INVESTIGATOR

Great Ormond Street Hospital for Children NHS Foundation Trust

Gill Smith, FRCS(Plast)

Role: PRINCIPAL_INVESTIGATOR

Great Ormond Street Hospital for Children NHS Foundation Trust

George Murphy, PhD FRCS

Role: PRINCIPAL_INVESTIGATOR

Great Ormond Street Hospital for Children NHS Foundation Trust

Lucy Cogswell, FRCS(Plas)

Role: PRINCIPAL_INVESTIGATOR

Oxford University Hospitals

Locations

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Oxford University Hospitals

Oxford, Oxfordshire, United Kingdom

Site Status RECRUITING

Royal Free Hospital

London, , United Kingdom

Site Status RECRUITING

Guy's and St Thomas' Hospital

London, , United Kingdom

Site Status RECRUITING

Chelsea and Westminster Hospital NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

Great Ormond Street Hospital for Children NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Malcolm Logan, BSc PhD

Role: CONTACT

02078486886

George Murphy, PhD FRCS

Role: CONTACT

Facility Contacts

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Lucy Cogswell, FRCS Plast

Role: primary

0300 304 7777

George Murphy, FRCS

Role: backup

Bran Sivakumar

Role: primary

02074059200 ext. 5222

George RF Murphy, MA

Role: primary

Gill Smith

Role: primary

Branavan Sivakumar

Role: primary

02074059200 ext. 5222

Gill Smith

Role: backup

02074059200 ext. 5222

Provided Documents

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Document Type: Study Protocol

View Document

Related Links

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http://congenitalhand.net/

Study website - for version control \& distribution of patient information leaflets / consent forms.

Other Identifiers

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15/LO/2085

Identifier Type: OTHER

Identifier Source: secondary_id

14SG01

Identifier Type: -

Identifier Source: org_study_id

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