Ignite Creation Date:
2024-05-06 @ 3:26 PM
Last Modification Date:
2024-10-26 @ 1:49 PM
Study NCT ID:
NCT04631471
Status:
RECRUITING
Last Update Posted:
2022-01-13
First Post:
2020-07-09
Brief Title:
Regeneration in Cervical Degenerative Myelopathy
Sponsor:
Cambridge University Hospitals NHS Foundation Trust
Organization:
Cambridge University Hospitals NHS Foundation Trust
Study Overview
Official Title:
Regeneration in Cervical Degenerative Myelopathy - a Multi-centre Double-blind Randomised Placebo Controlled Trial Assessing the Efficacy of Ibudilast as an Adjuvant Treatment to Decompressive Surgery for Degenerative Cervical Myelopathy
Status:
RECRUITING
Status Verified Date:
2021-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RECEDE
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 100000 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
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 100000 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
Detailed Description:
DCM is a common disabling disease It is also a major cause of gait disturbance and imbalance in the elderly As a consequence DCM contributes to reduced mobility and frailty NHS England recognises 1 reducing premature mortality and 2 enhancing quality of life for people with long-term conditions as important DCM patients are at risk of recurrent falls which is a major concern In fact a study investigating patients with hip fractures demonstrated that 25 of patients suffered from undiagnosed DCM Surgical decompression is the only form of treatment at present It is shown to stop disease progression However neurological recovery after surgery is often disappointing There are no approved drug treatments for DCM Alleviating the long-term disability caused by DCM represents an unmet clinical need Recovery of leg and arm function as well as an improvement in pain are the patient recovery priorities
In DCM mechanical pressure on the spinal cord causes progressive loss of nerve cells and their processes as well as loss of myelin sheaths the insulating layers of neurons formed by oligodendrocytes Surgical decompression can halt disease progression but there is limited natural spinal cord repair Preclinical studies demonstrated that inhibition of PDE4 is able to stimulate a regenerative response which is likely to benefit DCM remyelination and axonal plasticity Clinical studies using Ibudilast a phosphodiesterase 4 inhibitor have demonstrated beneficial effects in multiple sclerosis The observed beneficial effects are likely to reflect regeneration-inducing and neuroprotective effects of Ibudilast in the human CNS
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 The research questions have been designed to
Assess safety and tolerability of Ibudilast in patients undergoing surgery for DCM
Assess efficacy of Ibudilast treatment in patients undergoing surgery for DCM
Investigate disease mechanisms using
Advanced imaging techniques including MRI
Gait analysis
Explore the role of novel clinical outcome measures for studies investigating DCM
Clinical scales
Inform the design of future drug trials for use in DCM
Investigate the impact of DCM on carers
The following hypothesis will be addressed Ibudilast improves recovery following surgical decompression of degenerative cervical myelopathy
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 involving up to 10 UK sites A total of 362 participants will be recruited
Each participant will be on trial for approximately 15 months 21 days There is a maximum 1 week interval from screening to randomisation and a maximum 1 week interval from randomisation to treatment commencement Ibudilast treatment will start within 10 weeks prior to surgery and will continue for up to 24 weeks after surgery Treatment will be halted 5 days prior to surgery and resumed at the previous maximum dose as soon as possible after two days since the operation Participants will be taking Ibudilast for a maximum of 34 weeks in case surgery is delayed beyond 10 weeks post-surgery treatment will be shortened accordingly to keep the 34 weeks maximum treatment period Participants will be followed up for a maximum of 12 months after surgery
The trial aims to run in parallel to standard clinical care The only difference between the trial pathway and the standard NHS pathway is the addition of a course of either Ibudilast or placebo and the additional follow upDCM is typically managed in the outpatient setting Patients are referred to a surgeon for assessment and management Patients often already have a diagnosis Sometimes an allied professional makes a diagnosis acutely and a same day emergency referral is made to the regional spinal centre On occasion such a situation predicates urgent surgery but typically in such cases an outpatient appointment is made Patients will therefore be identified from participating neurosurgical centres typically via outpatient clinics but also the emergency referrals Screening of patients to determine eligibility for participation in the trial will be undertaken by the parent neurosurgical team according to the inclusion exclusion criteria Prior to screening patients with DCM will be approached by a delegated member of the local trial team and given a patient information sheet PIS to take away and read in their own time Patients will be advised to get in touch with the local trial team in order to address any questions that they may have on the contents of the PIS If they decide to participate in the trial they will be invited for a screening visit to provide a written informed consent and assess their eligibility for the trial as per inclusionexclusion criteria described below
Once informed consent is obtained screening assessments will be performed in the same outpatient clinic visit
Screening assessments to establish eligibility will include
Age
Medical History including but not limited to
Neurological Disorders
Respiratory Disorders
Diabetes Mellitus
Psychiatric Disorders
Smoking Status
DCM characteristics
Symptoms
Length of DCM symptoms
Date of DCM diagnosis
MRI image findings and causative pathology
Medication review including allergy status
Neurological examination
mJOA assessment
Laboratory Tests FBC LFT EUC
Pregnancy test serum beta HCG - if female of childbearing potential within 2 weeks of trial treatment start
ECG
Following screening assessments trial-specific baseline assessments will be conducted preferably on the same day
Demographics weight Kg sex ethnicity date of birth
Employment status
30m walk test
VAS pain
SF-36
EQ-5DHealth Resource usage
Carer QoL for sub-study
Review of potential AEs starting from point of giving informed consent
A serum sample will be taken for PK studies Optional but highly desirable assessments
GRASSP-Cervical Myelopathy
SCIMv3
NDI
Quick-DASH
At the end of the visit the dosing diary will be issued to the patient and instructed on how to use it Participants eligibility will be confirmed on receipt of results of the laboratory tests and they will be randomised to either Ibudilast or placebo Participants will start treatment no later than 2 weeks after screening visit One week after IMP delivery or collection the local research team will make contact with the participant by telephone to ensure they have received the IMP and commenced their trial treatment Any Adverse Events which may have occurred since consent will be documented in CRFs Surgery will be performed ideally within 10 weeks after start of trial treatment
Within 21 days prior to surgery patients will have an outpatient clinic pre-operative visit and the following assessments will be performed
Laboratory Tests FBC LFT EUC TFTs
Assessment of any change to Medical or Drug history
WHO performance status
Neurological examination
mJOA
30m walk test
VAS pain
SF-36
EQ-5DHealth Resource usage
Carer QoL for sub-study
Review of AEs
IMP compliance assessment participant medication diary review and capsule count
Respiratory Physiology
MRI
Gait Lab sub-study for Addenbrookes only
A serum sample for PK studies will be taken Optional but highly desirable assessments
GRASSP-Cervical Myelopathy
SCIMv3
NDI
Quick-DASH
Intra-operative assessments
Surgery details
Operation Title
Approach Anterior Posterior or Combined
Instrumented Procedure
Levels Treated
ASA
Intra-Operative Complications
A CSF sample will be taken if possible - optional
A paired serum sample for PK studies will be taken
Post-operative assessments on discharge within 14 days after surgery
Neurological examination
VAS Pain
Adverse Events including operative complications
IMP compliance assessment participant medication diary review and capsule count
Further IMP will be dispensed
Optional but highly desirable assessments
NDI
Follow Up assessments at 3 months post-surgery 21 days
Laboratory Tests FBC LFT EUC TFTs
Neurological examination
Medication review
mJOA
30m walk test
VAS pain
SF-36
Carer QoL for sub-study
Review of AEs
IMP compliance assessment participant medication diary review and capsule count
A serum sample for PK studies will be taken Further IMP will be dispensed Optional but highly desirable assessments
GRASSP-Cervical Myelopathy
NDI
EQ-5DHealth Resource usage
Quick-DASH
Gait Lab sub-study at Addenbrookes only
Follow Up assessments at 6 months post surgery 21 days
Laboratory Tests FBC LFT EUC TFTs
Neurological examination
Medication review
mJOA
30m walk test
VAS pain
SF-36
EQ-5DHealth Resource usage
Carer QoL for sub-study
Review of AEs
IMP compliance participant medication diary review and capsule count
Respiratory physiology
MRI
Gait lab sub-study at Addenbrookes only
A serum sample for PK studies will be taken Optional but highly desirable assessments
GRASSP-Cervical Myelopathy
SCIMv3
NDI
Quick-DASH
Follow Up assessments at 12 months post surgery 21 days
Laboratory Tests FBC LFT EUC TFTs
Medication review
Neurological examination
mJOA
30m walk test
VAS pain
SF-36
EQ-5DHealth Resource usage
Carer QoL for sub-study
Review of AEs
A serum sample for PK studies will be taken Optional but highly desirable assessments
GRASSP-Cervical Myelopathy
NDI
Quick-DASH
In DCM mechanical pressure on the spinal cord causes progressive loss of nerve cells and their processes as well as loss of myelin sheaths the insulating layers of neurons formed by oligodendrocytes Surgical decompression can halt disease progression but there is limited natural spinal cord repair Preclinical studies demonstrated that inhibition of PDE4 is able to stimulate a regenerative response which is likely to benefit DCM remyelination and axonal plasticity Clinical studies using Ibudilast a phosphodiesterase 4 inhibitor have demonstrated beneficial effects in multiple sclerosis The observed beneficial effects are likely to reflect regeneration-inducing and neuroprotective effects of Ibudilast in the human CNS
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 The research questions have been designed to
Assess safety and tolerability of Ibudilast in patients undergoing surgery for DCM
Assess efficacy of Ibudilast treatment in patients undergoing surgery for DCM
Investigate disease mechanisms using
Advanced imaging techniques including MRI
Gait analysis
Explore the role of novel clinical outcome measures for studies investigating DCM
Clinical scales
Inform the design of future drug trials for use in DCM
Investigate the impact of DCM on carers
The following hypothesis will be addressed Ibudilast improves recovery following surgical decompression of degenerative cervical myelopathy
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 involving up to 10 UK sites A total of 362 participants will be recruited
Each participant will be on trial for approximately 15 months 21 days There is a maximum 1 week interval from screening to randomisation and a maximum 1 week interval from randomisation to treatment commencement Ibudilast treatment will start within 10 weeks prior to surgery and will continue for up to 24 weeks after surgery Treatment will be halted 5 days prior to surgery and resumed at the previous maximum dose as soon as possible after two days since the operation Participants will be taking Ibudilast for a maximum of 34 weeks in case surgery is delayed beyond 10 weeks post-surgery treatment will be shortened accordingly to keep the 34 weeks maximum treatment period Participants will be followed up for a maximum of 12 months after surgery
The trial aims to run in parallel to standard clinical care The only difference between the trial pathway and the standard NHS pathway is the addition of a course of either Ibudilast or placebo and the additional follow upDCM is typically managed in the outpatient setting Patients are referred to a surgeon for assessment and management Patients often already have a diagnosis Sometimes an allied professional makes a diagnosis acutely and a same day emergency referral is made to the regional spinal centre On occasion such a situation predicates urgent surgery but typically in such cases an outpatient appointment is made Patients will therefore be identified from participating neurosurgical centres typically via outpatient clinics but also the emergency referrals Screening of patients to determine eligibility for participation in the trial will be undertaken by the parent neurosurgical team according to the inclusion exclusion criteria Prior to screening patients with DCM will be approached by a delegated member of the local trial team and given a patient information sheet PIS to take away and read in their own time Patients will be advised to get in touch with the local trial team in order to address any questions that they may have on the contents of the PIS If they decide to participate in the trial they will be invited for a screening visit to provide a written informed consent and assess their eligibility for the trial as per inclusionexclusion criteria described below
Once informed consent is obtained screening assessments will be performed in the same outpatient clinic visit
Screening assessments to establish eligibility will include
Age
Medical History including but not limited to
Neurological Disorders
Respiratory Disorders
Diabetes Mellitus
Psychiatric Disorders
Smoking Status
DCM characteristics
Symptoms
Length of DCM symptoms
Date of DCM diagnosis
MRI image findings and causative pathology
Medication review including allergy status
Neurological examination
mJOA assessment
Laboratory Tests FBC LFT EUC
Pregnancy test serum beta HCG - if female of childbearing potential within 2 weeks of trial treatment start
ECG
Following screening assessments trial-specific baseline assessments will be conducted preferably on the same day
Demographics weight Kg sex ethnicity date of birth
Employment status
30m walk test
VAS pain
SF-36
EQ-5DHealth Resource usage
Carer QoL for sub-study
Review of potential AEs starting from point of giving informed consent
A serum sample will be taken for PK studies Optional but highly desirable assessments
GRASSP-Cervical Myelopathy
SCIMv3
NDI
Quick-DASH
At the end of the visit the dosing diary will be issued to the patient and instructed on how to use it Participants eligibility will be confirmed on receipt of results of the laboratory tests and they will be randomised to either Ibudilast or placebo Participants will start treatment no later than 2 weeks after screening visit One week after IMP delivery or collection the local research team will make contact with the participant by telephone to ensure they have received the IMP and commenced their trial treatment Any Adverse Events which may have occurred since consent will be documented in CRFs Surgery will be performed ideally within 10 weeks after start of trial treatment
Within 21 days prior to surgery patients will have an outpatient clinic pre-operative visit and the following assessments will be performed
Laboratory Tests FBC LFT EUC TFTs
Assessment of any change to Medical or Drug history
WHO performance status
Neurological examination
mJOA
30m walk test
VAS pain
SF-36
EQ-5DHealth Resource usage
Carer QoL for sub-study
Review of AEs
IMP compliance assessment participant medication diary review and capsule count
Respiratory Physiology
MRI
Gait Lab sub-study for Addenbrookes only
A serum sample for PK studies will be taken Optional but highly desirable assessments
GRASSP-Cervical Myelopathy
SCIMv3
NDI
Quick-DASH
Intra-operative assessments
Surgery details
Operation Title
Approach Anterior Posterior or Combined
Instrumented Procedure
Levels Treated
ASA
Intra-Operative Complications
A CSF sample will be taken if possible - optional
A paired serum sample for PK studies will be taken
Post-operative assessments on discharge within 14 days after surgery
Neurological examination
VAS Pain
Adverse Events including operative complications
IMP compliance assessment participant medication diary review and capsule count
Further IMP will be dispensed
Optional but highly desirable assessments
NDI
Follow Up assessments at 3 months post-surgery 21 days
Laboratory Tests FBC LFT EUC TFTs
Neurological examination
Medication review
mJOA
30m walk test
VAS pain
SF-36
Carer QoL for sub-study
Review of AEs
IMP compliance assessment participant medication diary review and capsule count
A serum sample for PK studies will be taken Further IMP will be dispensed Optional but highly desirable assessments
GRASSP-Cervical Myelopathy
NDI
EQ-5DHealth Resource usage
Quick-DASH
Gait Lab sub-study at Addenbrookes only
Follow Up assessments at 6 months post surgery 21 days
Laboratory Tests FBC LFT EUC TFTs
Neurological examination
Medication review
mJOA
30m walk test
VAS pain
SF-36
EQ-5DHealth Resource usage
Carer QoL for sub-study
Review of AEs
IMP compliance participant medication diary review and capsule count
Respiratory physiology
MRI
Gait lab sub-study at Addenbrookes only
A serum sample for PK studies will be taken Optional but highly desirable assessments
GRASSP-Cervical Myelopathy
SCIMv3
NDI
Quick-DASH
Follow Up assessments at 12 months post surgery 21 days
Laboratory Tests FBC LFT EUC TFTs
Medication review
Neurological examination
mJOA
30m walk test
VAS pain
SF-36
EQ-5DHealth Resource usage
Carer QoL for sub-study
Review of AEs
A serum sample for PK studies will be taken Optional but highly desirable assessments
GRASSP-Cervical Myelopathy
NDI
Quick-DASH
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2017-004856-41 | EUDRACT_NUMBER | None | None |
| 213009 | REGISTRY | IRAS | None |