Regeneration in Cervical Degenerative Myelopathy

NCT04631471 | Recruiting Phase 3 DMC

• 3 other identifiers: CCTU01782017-004856-41213009
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

Degenerative (wear and tear arthritis of the spine) Cervical (concerning the neck) Myelopathy (injury to the spinal cord), DCM, is the most common spinal cord disorder of adulthood. In DCM, arthritis of the spine causes compression of the spinal cord. The symptoms of DCM are often mistaken for natural consequences of ageing, including numb and clumsy hands, loss of coordination, imbalance, bladder and bowel problems. The weakness can progress to severe paralysis. Every year approximately 4 individuals in 100,000 undergo surgery for DCM; however, many more individuals are thought to suffer from DCM. The main treatment for DCM is surgery. The aim of surgery is to create space and remove the compression of the spinal cord. This is known to prevent further injury. Unfortunately, the post-operative improvements are often incomplete and many patients remain severely disabled. Improving outcome after surgery represents an important unmet clinical need. Clinical and preclinical findings indicate that the drug Ibudilast can stimulate neuroprotective and regenerative processes in the spinal cord. Ibudilast is well-tolerated and used to treat asthma and post-stroke dizziness in Japan and is currently being investigated for use in treating other neurological diseases. This study will investigate whether daily oral administration of Ibudilast for a maximum of 34 weeks can improve hand function, strength, balance, urinary problems and reduce pain. The study will initially be conducted at three sites in the UK, with more sites added as necessary. Individuals between 18-80 years old, diagnosed with DCM and scheduled for an operation for the first time will be invited to participate in the trial. The study will entail patient questionnaires and clinical assessments before surgery, shortly after surgery and 3, 6, and 12 months after surgery. Moreover, patients will undergo MRI scans pre-operatively and at 6-months postoperatively to determine whether the treatment was successful.

Conditions

Myelopathy; Spinal Cord Diseases

Keywords

Degenerative; Cervical; Myelopathy

Outcome Measures

Primary Outcomes (2)

• Change in modified Japanese Orthopaedic Association (mJOA) scale

  The mJOA is an 18-point clinician administered scale (0 worst to 18 best), which evaluates motor dysfunction in upper and lower extremities, loss of sensation and sphincter dysfunction.

  From baseline to 6 months follow-up

• Change in Visual Analogue Scale (VAS) neck pain

  VAS Neck pain is a 10cm horizontal line, on which a patient indicates their level of neck pain from 0 (no pain) to 10 (worst pain).

  From baseline to 6 months follow-up

Secondary Outcomes (2)

• PCS-SF36

  From baseline to 6 months follow-up

• MCS-SF36

  From baseline to 6 months follow-up

Study Arms (2)

Ibudilast

ACTIVE COMPARATOR

Increasing dose of Ibudilast up to 100mg/day for up to 10 weeks prior to cervical decompressive surgery and up to 24 weeks after cervical decompressive surgery

Drug: Ibudilast; Procedure: Cervical decompressive surgery

Placebo

PLACEBO COMPARATOR

Increasing dose of matched placebo containing mannitol instead of ibudilast up to 10 pills/day for up to 10 weeks prior to cervical decompressive surgery and up to 24 weeks after cervical decompressive surgery

Procedure: Cervical decompressive surgery; Drug: Matching placebo

Interventions

Ibudilast DRUG

Increasing dose of ibudilast from 60mg/6 capsules per day to 100mg/10 capsules per day to be started up to 10 weeks prior to surgery. Treatment will continue up to 24 weeks after surgery. Maximum treatment period will be of 34 weeks.

Ibudilast

Cervical decompressive surgery PROCEDURE

Surgical decompression of degenerate cervical myelopathy

Ibudilast; Placebo

Matching placebo DRUG

Increasing dose of matching placebo from 6 capsules per day to 10 capsules per day to be started up to 10 weeks prior to surgery. Treatment will continue up to 24 weeks after surgery. Maximum treatment period will be of 34 weeks.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients suffering from degenerative cervical myelopathy as per established criteria who have granted informed consent to participate in the trial
• Have a preoperative mJOA score ≥8 and ≤14
• Scheduled for first surgical decompression as part of usual NHS clinical practice

You may not qualify if:

• 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
• 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 study 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 study 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 study drug
• Unable to converse, read or write English at primary school level

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead

Study Sites (1)

Addenbrooke's Hospital

Cambridge, CB20QQ, United Kingdom

RECRUITING

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MeSH Terms

Conditions

Spinal Cord Diseases

Interventions

ibudilast

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Benjamin Davies, MD

  Cambridge University Hospital, Department of Neurosurgery

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark R Kotter, PhD

CONTACT

+44 1223 747476; mrk25@cam.ac.uk

Paula Kareclas, PhD

CONTACT

01223254684; paula.kareclas@addenbrookes.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Investigator

Model Details: Placebo controlled trial

Study Record Dates

• First Submitted: July 9, 2020
• First Posted: November 17, 2020
• Study Start: December 22, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: January 13, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)