RECEDE – Myelopathy

REgeneration in CErvical DEgenerative Myelopathy

Research summary

Degenerative Cervical Myelopathy (DCM) is a crippling disease with severe impact on quality of life. It is caused by compression of the cervical spinal cord from wear and tear changes in the surrounding spinal structures. Chronic compression of the spinal cord can result in progressive neurological deficits and paralysis. Typically, individuals with DCM present with numb and clumsy hands, imbalance, frequent falls, loss of mobility, urinary incontinence and pain. The initial symptoms of DCM are often mistaken for a natural consequence of ageing, but as they progress patients can end up paralysed.

The proposed trial is the first regenerative treatment for DCM, and potentially the first drug-based regenerative treatment for neurosurgical disease. It will mark an important milestone with regard to translation of preclinical findings into a clinical setting. RECEDE-Myelopathy is a multi-centre, double blind, phase III randomised, placebo controlled trial assessing the use of Ibudilast as an adjuvant treatment to decompressive surgery for DCM. It will commence with a pilot to assess trial feasibility (Stage 1), which will be followed by the substantive trial (Stage 2) if the progression criteria are met.

clinicaltrials.gov

Main inclusion criteria

To be included in the trial the patient must fulfil the following criteria:

  • Male or female, between 18 and 80 years old

  • Diagnosis of symptomatic degenerative cervical myelopathy (at least one feature from each of the three categories below):

  1. Clinical symptoms

    • Numb hands

    • Clumsy hands

    • Bilateral Arm Paraesthesia

    • Gait impairment

    • Lhermitte’s Phenomenon

    • Weakness

  2. Neurological signs

    • Pyramidal weakness

    • Hyperreflexia

    • Positive Hoffman sign

    • Upgoing Plantar Response

    • Atrophy of intrinsic hand muscles

    • Spasticity/Clonus

    • Broad based, unstable gait

  3. MRI Indicators

    • Effacement of CSF and deformation of cord

    • T1 or T2 Cord Signal Change

    • Segmentation of T2 Signal Change

    • Reduction in transverse area of cord

    • Scheduled for first surgical decompression as part of usual clinical practice

    • Preoperative mJOA score ≥8 and ≤14

Main exclusion criteria

The presence of any of the following will preclude patient inclusion:

  • Previous surgery for DCM

  • DCM symptoms due to cervical trauma (at the discretion of the investigator)

  • Hypersensitivity to Ibudilast or any of the formulation components

  • Evidence of acute hepatitis, clinically significant chronic hepatitis, or evidence of clinically significant impaired hepatic function through clinical and laboratory evaluation including ALP> 1.5x ULN; ALT or AST > 2x ULN; GGT > 3x ULN

  • Evidence of thrombocytopenia at screening through laboratory evaluation including platelet count <5000

  • Active malignancy defined as history of invasive malignancy, except if the patient has received treatment and displayed no clinical signs and symptoms for at least five years

  • Recent history (less than 3 years) of chemical substance dependency or significant psychosocial disturbance that may impact the outcome or trial participation

  • Female patients with child bearing potential who are unwilling or unable to use reliable methods of contraception

  • Female patients who are pregnant, lactating or planning pregnancy during the course of the trial

  • Inability to comply with trial procedures, IMP regime or follow-up schedule

  • Unable to take a gelatin based product

  • Participation in another CTIMP or device within the past 30 days from the time of recruitment

  • Functional disability from a commitment neurological disease that would mask the symptoms of DCM (at the discretion of the investigator). Including but not limited to stroke with residual disability, cerebellar ataxia, Parkinson’s disease, symptomatic lumbar stenosis and multiple sclerosis

  • Resting pulse < 50 bpm, SA or AV block, uncontrolled hypertension, or QTcF > 450 ms

  • History of stomach or intestinal surgery or any other condition that could interfere with or is judged by the Investigator to interfere with absorption, distribution, metabolism, or excretion of IMP

  • Unable to converse, read or write English

Chief investigator

Dr Mark Kotter

Contact details

Clinical Trials Coordinator: Paula Turnbull

Telephone: 01223 596473 | Email: [email protected]