Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000796785p
Ethics application status
Submitted, not yet approved
Date submitted
17/04/2022
Date registered
7/06/2022
Date last updated
7/06/2022
Date data sharing statement initially provided
7/06/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The Conceal Trial - Targeted Muscle Re-innervation (TMR) in the treatment of chronic neuropathic and phantom limb pain following a major lower limb amputation
Scientific title
The Conceal Trial - Targeted Muscle Re-innervation (TMR) in the treatment of chronic neuropathic and phantom limb pain following a major lower limb amputation
Secondary ID [1] 306953 0
Nil known
Universal Trial Number (UTN)
Nil known
Trial acronym
None
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Chronic neuropathic pain 326066 0
Phantom limb pain 326067 0
Lower limb amputation 326068 0
Targeted Muscle Re-innervation 326069 0
Condition category
Condition code
Surgery 323377 323377 0 0
Surgical techniques

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Targeted Muscle re-innervation (TMR):
- In this technique, the neuroma is excised and the distal end of the newly freshened nerve in the amputated stump is coapted to nearby motor nerves that now innervate redundant muscle
- The neuroma is identified using Tinel's sign
- The motor nerve branches in the target muscle are located via a hand held nerve stimulator
- This operation takes approximately 1.5 - 2 hours
- It is performed by a plastic surgeon who is already trained in this technique
- Importantly, patients in the treatment group (and control group) will not be permitted to undergo use of paralytic agents or nerve blocks peri-operatively or use of a torniquet intra-operatively
- Patients will have a drain inserted into the stump prior to closure
- The stump will be closed and dressed
Intervention code [1] 323399 0
Treatment: Surgery
Comparator / control treatment
The control group will also undergo surgery to isolate the neuroma responsible for the chronic neuropathic pain but will not undergo any specific intervention or treatment for the neuroma specifically.
Control group
Placebo

Outcomes
Primary outcome [1] 331113 0
Pain - this will be assessed via the Numerical rating scale
Timepoint [1] 331113 0
Pre-operatively

Post-operatively at 1, 3, 6, 12 months
Primary outcome [2] 331516 0
PROMIS pain scale
Timepoint [2] 331516 0
Pre-opertaively

Post-operatively at 1, 3, 6, 12 months
Primary outcome [3] 331517 0
Neuro-QOL - lower extremity function
Timepoint [3] 331517 0
Pre-operatively

Post-operatively at 1, 3, 6, 12 months
Secondary outcome [1] 408797 0
Functional brain MRI
Timepoint [1] 408797 0
Pre-operatively

Post- operatively at 12 months
Secondary outcome [2] 410145 0
Structural brain MRI
Timepoint [2] 410145 0
Pre-operatively

Post-operatively at 12 months

Eligibility
Key inclusion criteria
Patients who have undergone a major lower limb amputation in the last 5 years and currently diagnosed with chronic neuropathic and phantom limb pain, but who have not undergone previous surgical intervention to treat their neuropathic and phantom limb pain
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with cognitive impairment
Patients with a mental health disorder
Patients unable to proceed with a brain MRI
Patients unsafe to cease their antiplatelet or anticoagulant medication
Patients with previous medication abuse or IV drug use

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be recruited into the study by the Clinical Principle Investigator. At the time of recruitment, the Clinical Principle Investigator will be unaware to which group (control or treatment) the subject will be allocated to. Allocation will be determined at a later date in theatre, immediately following anaesthetic induction.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
Statistician statement:

Sample size:
The planned sample size for the trial is 30 patients (15 per group). Due to the exploratory nature of this study, effect sizes will be reported in terms of standard deviations of the outcome variable. With 15 subjects per group this study will have an 80% power to detect a difference in continuous variables equivalent to 1.06 standard deviation units with a 2-sided p-value of 0.05. A difference of this magnitude is perceived to be of clinical importance.

Randomisation method:
A computer generated list of random treatment allocations (a randomisation schedule) will be used to assign patients to treatment in a 1:1 ratio.

Paul Eldho, PhD
Research Fellow
Monash Centre for Health Research and Implementation - MCHRI
School of Public Health and Preventive Medicine
Monash University
Level 1, Monash Health Research Precinct
43-51 Kanooka Grove
Monash Medical Centre
Clayton VIC 3168

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2022
Actual
Date of last participant enrolment
Anticipated
1/12/2022
Actual
Date of last data collection
Anticipated
1/12/2023
Actual
Sample size
Target
25
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 311271 0
Self funded/Unfunded
Name [1] 311271 0
Country [1] 311271 0
Primary sponsor type
Hospital
Name
Monash Health
Address
246 Clayton Road, Clayton, Victoria, 3168
Country
Australia
Secondary sponsor category [1] 312630 0
None
Name [1] 312630 0
Address [1] 312630 0
Country [1] 312630 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 310779 0
Monash Health
Ethics committee address [1] 310779 0
246 Clayton Road, Clayton, Victoria 3168
Ethics committee country [1] 310779 0
Australia
Date submitted for ethics approval [1] 310779 0
29/05/2022
Approval date [1] 310779 0
Ethics approval number [1] 310779 0

Summary
Brief summary
This blinded, randomised controlled trial aims to test if the intervention of TMR, targeted muscle re-innervation, a technique involving excision of the neuroma and coaptation of the freshened nerve end to nearby motor nerves in the stump denervated muscle, is effective in the treatment of chronic residual neuropathic and phantom limb pain in patients following a major lower limb amputation. Patients in the control group will undergo surgery to isolate the neuroma without TMR surgery. Patients in the treatment group will undergo surgery to isolate the neuroma plus TMR surgery. Patients in both groups will undergo pre-operative and post-operative pain and function questionnaires as well as functional and structural brain MRI to determine the effects of TMR on chronic neuropathic and phantom limb pain.
Trial website
Trial related presentations / publications
Public notes
Following a major limb amputation, the necessary cutting of nerves can cause faulty nerve regeneration resulting in the formation of structures called neuromas which are essentially nerves encased in a scar. These neuromas can cause pain in the remaining stump (residual neuropathic pain) or perceived discomfort in the involved limb (phantom pain). Several surgical treatment strategies developed to treat these neuromas have been described in the literature however they have largely been unsuccessful in preventing the re-formation of neuromas and the recurrence of symptoms. This is because these techniques, which usually involve excising the neuroma and burying it into one of a number of environments (muscle, bone, nerves) does not allow the nerve to regenerate appropriately or for another neuroma to develop. One technique that has shown promising results in the literature is a technique called targeted muscle re-innervation (TMR). This technique has shown to be promising in treating neuropathic and phantom limb pain as it does not simply result in excision of the neuroma and burying of the nerve end but channeling the nerve end towards nerve receptors in denervated muscle following limb amputation. Since its description in 2002, there has been only one randomised controlled trial in the world attempting to test the efficacy of TMR however this was a poorly designed trial with two different surgical techniques being tested in the trial without appropriate control groups. The conceal trial will be the first appropriately designed blinded, randomised controlled trial in the world to test the efficacy of TMR with an appropriate control and treatment groups. The conceal trial will involve two groups of patients. One group will be the control group who will undergo surgery to isolate the neuroma without TMR. The second group will be the treatment group who will undergo surgery to isolate the neuroma plus TMR. Patients will be randomised to their allocated group immediately after anaesthetic induction in theatre and will remain blinded to their allocated group for the life of the trial, which is expected to be in the order of 12 months. Over the next 12 months, patients will complete pain and function questionnaires at 3 monthly intervals to subjectively indicate any improvement in their level of pain and function as well any reduction in their medication usage. For the first time in the world, patients in both the control and treatment groups will undergo functional and structural brain MRI pre-operatively and post-operatively (at 12 months) to objectively measure any improvement in their chronic neuropathic and phantom limb pain. This neuroimaging has the potential to provide not only important information about how chronic neuropathic and phantom limb pain are processed in the central nervous system in patients following a major limb amputation in the context of TMR but also help to determine which patients are likely to benefit from this procedure in the future with the added possibility of tailoring the TMR technique to the individual patient. At the completion of the trial, patients in the control group will also have the opportunity to undergo the TMR procedure if the results of the trial indicate that TMR significantly improves chronic neuropathic residual limb pain and phantom limb pain. The results of this high quality randomised controlled trial with appropriate control groups will enable surgeons to practice evidence based medicine rather than depend on the currently inadequate prospective and retrospective studies which must be interpreted with caution given the inherent lack of controls groups.

Contacts
Principal investigator
Name 118834 0
Dr Mitra Rahmatzadeh
Address 118834 0
Department of Vascular Surgery
Monash Health
246 Clayton Road, Clayton, Victoria 3168
Country 118834 0
Australia
Phone 118834 0
+61 405141456
Fax 118834 0
Email 118834 0
mitra.rahmatzadeh@monashhealth.org
Contact person for public queries
Name 118835 0
Dr Mitra Rahmatzadeh
Address 118835 0
Department of Vascular Surgery
Monash Health
246 Clayton Road, Clayton, Victoria 3168
Country 118835 0
Australia
Phone 118835 0
+61 405141456
Fax 118835 0
Email 118835 0
mitra.rahmatzadeh@monashhealth.org
Contact person for scientific queries
Name 118836 0
Dr Mitra Rahmatzadeh
Address 118836 0
Department of Vascular Surgery
Monash Health
246 Clayton Road, Clayton, Victoria 3168
Country 118836 0
Australia
Phone 118836 0
+61 405141456
Fax 118836 0
Email 118836 0
mitra.rahmatzadeh@monashhealth.org

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Intellectual property ownership


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.