Ignite Creation Date:
2024-05-06 @ 8:26 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06387914
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2024-04-29
First Post:
2024-04-09
Brief Title:
Efficacy of Pain Intervention With Deep Brain Stimulation Neuromodulation
Sponsor:
University of Oxford
Organization:
University of Oxford
Study Overview
Official Title:
Efficacy of Pain Intervention With Deep Brain Stimulation Neuromodulation
Status:
ENROLLING_BY_INVITATION
Status Verified Date:
2024-08
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:
EPIONE
Brief Summary:
The goal of this clinical trial is to learn if deep brain stimulation DBS works to treat severe pain following a stroke in adults It will also learn about the safety of deep brain stimulation The main questions it aims to answer are
Does DBS lower the pain score in these participants
What medical problems do participants have when having DBS Researchers will compare different settings to see if DBS works to treat severe post stroke pain
Participants will
Undergo baseline screening procedures and have an MRI scan
Have neurosurgery to put the DBS system in
Have follow up for 10 months
Visit the clinic at least 5 times in the study for check-ups and tests
Fill in questionnaires about pain and mood and have check ups remotely
Does DBS lower the pain score in these participants
What medical problems do participants have when having DBS Researchers will compare different settings to see if DBS works to treat severe post stroke pain
Participants will
Undergo baseline screening procedures and have an MRI scan
Have neurosurgery to put the DBS system in
Have follow up for 10 months
Visit the clinic at least 5 times in the study for check-ups and tests
Fill in questionnaires about pain and mood and have check ups remotely
Detailed Description:
The EPIONE trial is a double blind randomised controlled crossover trial Comparing DBS stimulation with Pseudo-ON stimulation in participants who have central post stroke pain refractory to best medicalnon-medical therapy All participants will have the device on with different stimulation parameters depending on the phase during the trial Blinding refers to knowledge of stimulation parameters Following the randomised crossover periods stimulation is further honed refined for an additional period of 6 months called the optimisation period This may include making use of circadian and motion sensing features of the Picostim DyNeuMo-1 device for example to increase stimulation during sleep or movement as appropriate to the individuals symptoms
Existing evidence for the efficacy of DBS for chronic post stroke pain
Modern DBS efficacy trials often include a single- or double-blind design with a sham stimulation or crossover phase Strict case ascertainment criteria are also typically used Unlike these modern trials most pain DBS trials are uncontrolled case series or case reports with non-standardised recruitment criteria and considerable heterogeneity between cases hence the need for trials of DBS for pain that meets current scientific standards
A number of open-labelled studies have demonstrated moderate efficacy of DBS for chronic pain including CPSP A meta-analysis published in 2005 described the results of 424 cases pooled from 6 studies Sites of stimulation included the periaqueductalperiventricular grey PAGPVG the sensory thalamus and the internal capsule IC The authors noted that techniques used to assess pain severity were too heterogeneous to compare between studies The meta-analysis showed that trial stimulation was successful in 50 of patients with central pain ie CPSP and in the patients with successful trial stimulation who went on to implantation 58 reported ongoing pain relief Thus according to this meta-analysis the overall percentage of patients with CPSP who benefitted from DBS was 31 but the proportion receiving benefit was much higher in those with a positive response to test stimulation 58 This meta-analysis highlights the importance of being able to pre-select patients most likely to have successful trial stimulation which the investigators hope to address in the present trial
A subsequent trial reported the results of a series of 56 patients who received DBS for chronic pain of whom 11 had central post-stroke pain Only 211 had successful test stimulation but the two who had DBS implanted reported ongoing pain relief Another open label single centre trial reported early improvements in 696 of patients with chronic post-stroke pain who underwent DBS and of patients who retained their DBS stimulators at 1 year there was a significant improvement in pain VAS score p 0001 A case series of 4 patients with intractable pharmacologically resistant hemi-body thalamic pain lasting for at least 2 years Three of these patients had post-stroke pain Post DBS assessments were at 36 and 12 months Three patients achieved long-lasting pain relief of more than 40 at 3 6 and 12 months
A recent assessor-blinded randomized controlled crossover trial of DBS for post-stroke pain targeting the ventral striatumanterior limb of the internal capsule VSALIC is a unique and pioneering example of a controlled trial of DBS for chronic pain In this trial of 9 patients it was demonstrated that DBS was associated with significant improvements in scores on the Montgomery-Asberg Depression Rating Scale the Beck Depression Inventory and the McGill Affective pain rating index although the primary outcome of 50 pain relief was not achieved No similar trial design has been employed to test the efficacy of more traditional targets for pain DBS- namely the PAG and the sensory thalamus The aim of this trial is to build on the methodology demonstrated in previous trials applying it to PAG and sensory thalamus stimulation
The explanation for variability in outcomes of different trials of DBS for CPSP is not clear However important methodological differences exist between studies over crucial issues of patient selection pre-operative opioid reduction and assessment of outcome Blinding and sham stimulation are generally absent from reports of DBS for chronic pain although blinded clinical evaluations of efficacy have been carried out It is of great importance to conduct a prospective randomized controlled cross over trial for chronic pain in a selected chronic pain subgroup ie chronic post-stroke pain using traditional DBS targets ie PAG and sensory thalamus It is also crucial that careful analysis of pre-operative structural imaging and pain assessments are conducted to help develop algorithms that can predict which patients are likely to have positive responses to test stimulation as this ability would greatly improve operative outcome data and enable surgeons to avoid surgery in patients unlikely to benefit
Rationale for the EPIONE trial The timing of this trial is apt given a recent evaluation of non-surgical therapies for chronic pain by NICE which indicated many current treatments are poorly effective NICE NG193 This trial may offer evidence for the role of surgical therapy in chronic pain which has been approved by NICE historically NICE IPG382 but not found to be cost effective due to lack of evidence Deep brain stimulation surgery offers an opportunity to provide randomised blinded controlled trial designs since the surgery is not the treatment itself rather the neurostimulation provided by the implanted system is the treatment Participants and assessors of the clinical effect can be blinded to stimulation parameters and participants can be randomised to different settings at different time points The investigators have sought to use these features of neurostimulation surgery to generate high quality evidence to support or refute the use of DBS neurosurgery for chronic pain
Patients in the trial will undergo MRI brain imaging carried out for surgical planning The investigators will use structural and DTI scans of brain structure to determine whether there are any pre-existing brain changes that predict whether a patient will have a successful or unsuccessful response to stimulation Developing algorithms which incorporate imaging data to predict response to test stimulation will help to pre-select patients most likely to benefit from DBS in the future if the trial is successful It will also help to understand more about the mechanism of action of DBS for pain
There is clinical equipoise in this trial Although the investigators have seen in large prospective cohort studies that stimulation can treat pain well in a significant proportion of patients the investigators do not know if its efficacy can be demonstrated in a randomised controlled trial which provides the level of evidence required to justify its use in the National Health Service NHS The investigators are also aware stimulation can cause unwanted side effects in some patients especially at higher power settings which might make any treatment effect intolerable - some participants may prefer not to have stimulation The purpose of comparing two settings during the randomisationcrossover phase is to assess if appropriate stimulation is effective on average at treating CPSP without intolerable side effects before progressing to stimulation optimisation Given the economic burden of the disease economic outcome data will also be collated throughout the trial
Existing evidence for the efficacy of DBS for chronic post stroke pain
Modern DBS efficacy trials often include a single- or double-blind design with a sham stimulation or crossover phase Strict case ascertainment criteria are also typically used Unlike these modern trials most pain DBS trials are uncontrolled case series or case reports with non-standardised recruitment criteria and considerable heterogeneity between cases hence the need for trials of DBS for pain that meets current scientific standards
A number of open-labelled studies have demonstrated moderate efficacy of DBS for chronic pain including CPSP A meta-analysis published in 2005 described the results of 424 cases pooled from 6 studies Sites of stimulation included the periaqueductalperiventricular grey PAGPVG the sensory thalamus and the internal capsule IC The authors noted that techniques used to assess pain severity were too heterogeneous to compare between studies The meta-analysis showed that trial stimulation was successful in 50 of patients with central pain ie CPSP and in the patients with successful trial stimulation who went on to implantation 58 reported ongoing pain relief Thus according to this meta-analysis the overall percentage of patients with CPSP who benefitted from DBS was 31 but the proportion receiving benefit was much higher in those with a positive response to test stimulation 58 This meta-analysis highlights the importance of being able to pre-select patients most likely to have successful trial stimulation which the investigators hope to address in the present trial
A subsequent trial reported the results of a series of 56 patients who received DBS for chronic pain of whom 11 had central post-stroke pain Only 211 had successful test stimulation but the two who had DBS implanted reported ongoing pain relief Another open label single centre trial reported early improvements in 696 of patients with chronic post-stroke pain who underwent DBS and of patients who retained their DBS stimulators at 1 year there was a significant improvement in pain VAS score p 0001 A case series of 4 patients with intractable pharmacologically resistant hemi-body thalamic pain lasting for at least 2 years Three of these patients had post-stroke pain Post DBS assessments were at 36 and 12 months Three patients achieved long-lasting pain relief of more than 40 at 3 6 and 12 months
A recent assessor-blinded randomized controlled crossover trial of DBS for post-stroke pain targeting the ventral striatumanterior limb of the internal capsule VSALIC is a unique and pioneering example of a controlled trial of DBS for chronic pain In this trial of 9 patients it was demonstrated that DBS was associated with significant improvements in scores on the Montgomery-Asberg Depression Rating Scale the Beck Depression Inventory and the McGill Affective pain rating index although the primary outcome of 50 pain relief was not achieved No similar trial design has been employed to test the efficacy of more traditional targets for pain DBS- namely the PAG and the sensory thalamus The aim of this trial is to build on the methodology demonstrated in previous trials applying it to PAG and sensory thalamus stimulation
The explanation for variability in outcomes of different trials of DBS for CPSP is not clear However important methodological differences exist between studies over crucial issues of patient selection pre-operative opioid reduction and assessment of outcome Blinding and sham stimulation are generally absent from reports of DBS for chronic pain although blinded clinical evaluations of efficacy have been carried out It is of great importance to conduct a prospective randomized controlled cross over trial for chronic pain in a selected chronic pain subgroup ie chronic post-stroke pain using traditional DBS targets ie PAG and sensory thalamus It is also crucial that careful analysis of pre-operative structural imaging and pain assessments are conducted to help develop algorithms that can predict which patients are likely to have positive responses to test stimulation as this ability would greatly improve operative outcome data and enable surgeons to avoid surgery in patients unlikely to benefit
Rationale for the EPIONE trial The timing of this trial is apt given a recent evaluation of non-surgical therapies for chronic pain by NICE which indicated many current treatments are poorly effective NICE NG193 This trial may offer evidence for the role of surgical therapy in chronic pain which has been approved by NICE historically NICE IPG382 but not found to be cost effective due to lack of evidence Deep brain stimulation surgery offers an opportunity to provide randomised blinded controlled trial designs since the surgery is not the treatment itself rather the neurostimulation provided by the implanted system is the treatment Participants and assessors of the clinical effect can be blinded to stimulation parameters and participants can be randomised to different settings at different time points The investigators have sought to use these features of neurostimulation surgery to generate high quality evidence to support or refute the use of DBS neurosurgery for chronic pain
Patients in the trial will undergo MRI brain imaging carried out for surgical planning The investigators will use structural and DTI scans of brain structure to determine whether there are any pre-existing brain changes that predict whether a patient will have a successful or unsuccessful response to stimulation Developing algorithms which incorporate imaging data to predict response to test stimulation will help to pre-select patients most likely to benefit from DBS in the future if the trial is successful It will also help to understand more about the mechanism of action of DBS for pain
There is clinical equipoise in this trial Although the investigators have seen in large prospective cohort studies that stimulation can treat pain well in a significant proportion of patients the investigators do not know if its efficacy can be demonstrated in a randomised controlled trial which provides the level of evidence required to justify its use in the National Health Service NHS The investigators are also aware stimulation can cause unwanted side effects in some patients especially at higher power settings which might make any treatment effect intolerable - some participants may prefer not to have stimulation The purpose of comparing two settings during the randomisationcrossover phase is to assess if appropriate stimulation is effective on average at treating CPSP without intolerable side effects before progressing to stimulation optimisation Given the economic burden of the disease economic outcome data will also be collated throughout the trial
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 |
|---|---|---|---|
| 23WM0219 | OTHER | Ethics Committee South Birmingham REC UK | None |