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MCDS-Therapy

  • Research type

    Research Study

  • Full title

    An open label phase I/IIa trial repurposing carbamazepine (CBZ) for the treatment of skeletal dysplasia in children.

  • IRAS ID

    244715

  • Contact name

    Michael Wright

  • Contact email

    Michael.Wright19@nhs.net

  • Sponsor organisation

    The Newcastle upon Tyne Hospitals NHS Foundation Trust

  • Eudract number

    2018-002633-38

  • Duration of Study in the UK

    4 years, 0 months, 30 days

  • Research summary

    The aim of the MCDS therapy study is to evaluate the effect of carbamazepine on children with a diagnosis of Metaphyseal Chrondrodysplasia Schmid Type (MCDS) with confirmed COL10A1 pathogenic mutation. There is currently no specific treatment for patients with MCDS, and patient care is based only on the management of symptoms.

    The study is based on the results of preclinical studies, which support the efficacy of carbamazepine on cells and on mice with a COL10A1 mutation, both at a molecular level on the pathogenic mechanism reducing ER stress, and on growth and bone alignment in mice.

    Carbamazepine (CBZ) is a well-established drug, which has been widely marketed throughout Europe since the 1960s and is routinely used in paediatric care for the treatment of epilepsy and neuropathic pain. It has a well-known safety profile. There is no clinical reason to expect a different safety profile of CBZ in patients with MCDS compared to patients of similar ages treated with CBZ for epilepsy. Its effects on patients with MCDS have never been investigated.

    The study involves children with MCDS, as to evaluate the effect of CBZ on growth and bone alignment it is necessary to evaluate this on patients who have not reached bone maturity. The study aims to recruit 40 patients

    This is a multicentre international clinical trial. All clinical centres are regional or national referral centres for the diagnosis and management of patients with Genetic Skeletal Diseases including MCDS.

    The two-stage study will last a total of 60 months and will be comprised of an initial dose determination stage in a cohort of 12 patients (12 months)followed by long-term assessment of efficacy and safety at the chosen dose in a cohort of 28 patients (24 months).

  • REC name

    Yorkshire & The Humber - Sheffield Research Ethics Committee

  • REC reference

    18/YH/0428

  • Date of REC Opinion

    19 Nov 2018

  • REC opinion

    Favourable Opinion