Ignite Creation Date:
2024-05-06 @ 8:28 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06395649
Status:
RECRUITING
Last Update Posted:
2024-06-28
First Post:
2024-04-29
Brief Title:
Personalized Treatment by rTMS in Chronic Pain
Sponsor:
Aalborg University
Organization:
Aalborg University
Study Overview
Official Title:
Personalized Pain Treatment by Transcranial Magnetic Stimulation in Patients With Chronic Pain a Study on Mechanisms
Status:
RECRUITING
Status Verified Date:
2024-06
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:
PersoNINpain
Brief Summary:
Previous research has shown the effectiveness of magnetic stimulation of the brain as a supplemental treatment for various conditions such as depression and chronic pain However the application of magnetic stimulation has been standardized across patients without considering individual differences This one-size-fits-all approach results in only half of the patients benefiting from the treatment with the other half seeing no improvement in their symptoms Therefore a study on individuals with chronic pain will be performed to explore how magnetic stimulation treatments can be tailored to each person This will involve analyzing brain signal measurements before the start of the therapy and adjustingpersonalizing the magnetic stimulations to each individual person
Detailed Description:
This project aims to test if the effects of non-pharmacological non-invasive pain treatment can be enhanced by employing brain connectivity information to guide the application of repetitive transcranial magnetic stimulation rTMS Previous efficacy and safety trials have supported that rTMS for pain relief is applied to four main cortical areas primary motor cortex M1 dorsolateral prefrontal cortex DLPFC anterior cingulate cortex ACC and posterosuperior insular PSI However some patients respond to rTMS to one of these targets but not to the others Since there is no current strategy to know which patient will respond to each treatment target patients with chronic pain end up undergoing trial and error strategies which delay their improvement This is actually not different from challenges related to pharmacological treatment where each medication only relieves pain in 30-40 of patients and the choice of each medication is based on trial-and-error basis
Several strategies currently aim to provide a more individualized strategy for choosing analgesic interventions based on patient-related information In order to allow for the design of efficacy trials in the future the present project is based on a proof-of-concept mechanistic design It will employ rTMS stimulation for pain control but the choice of each of the stimulation targets will be made based on each individuals brain signals as read by EEG recorded before the start of the treatment Therefore before receiving a full rTMS treatment patients will undergo a neurophysiological screening session using single-pulseTMS-EEG Single-pulseTMS and EEG have been routinely used in the clinic as a part of the neurophysiological assessment of patients for decades but have not yet been used in the association as an attempt to try to guide the choice of treatment In the screening session single pulses TMS will be applied to each of the primary network hubs used in therapeutic rTMS M1 DLPFC ACC and PSI Concomitantly the EEG oscillatory activity of these four cortical areas will be recorded and the brain connectivity state will be assessed By using information derived from a patients brain connectivity state using transcranial magnetic stimulation with electroencephalography TMS-EEG the most appropriate of the four classic targets will be selected and used in rTMS on an individualized basis It is hypothesized that the brain regions with low local-to-global connectivity will provide better pain relief compared to non-personalized treatment approaches and compared to targets with optimized local-to-global connectivity status
A total of 90 subjects with chronic pain will be included in a double-blind randomized three parallel-arm study comparing the analgesic effect of the therapeutic rTMS target chosen based on TMS-EEG
1 target area presenting the lowest local-to-global connectivity
2 target area presenting the highest local-to-global connectivity
3 classic M1 stimulation
The subjects will be allocated in a 111 ratio to one of three arms 30 subjects per arm The protocol is designed as an adaptive study incorporating interim analyses after enrolling 30 and 60 subjects These evaluations conducted by a blinded specialist statistician panel will assess the efficacy of the target selection strategy for each arm focusing on the primary outcomes progression
In the initial baseline measurement the subjects will fill out questionnaires and undergo neurophysiological assessments After this baseline measurement the subjects will be assigned to one of the three arms and will receive daily rTMS sessions targeting areas called induction phase for 5 consecutive days Monday to Friday with either high connectivity low connectivity or a classic M1 target Each of the 5 daily stimulations will last 30 minutes of which 15 minutes will be under treatment
The induction phase will be followed by a 6-week maintenance phase with 1 rTMS session per week totaling 6 rTMS sessions At the end of the maintenance phase primary and secondary outcomes questionnaires will be collected to investigate the efficacy of the rTMS treatments A random subsample of 30 participants 10 from each arm will be asked if they would like to participate in a second 3-hour neurophysiological assessment to investigate the changes in brain connectivity
Subjects experiencing significant pain reduction according to the primary outcome by the treatment will be asked if they would like to continue maintenance stimulation sessions Participants accepted to join this part of the study will receive 1 stimulation session every 2 weeks for 4 weeks total of 2 stimulation sessions The participants will receive either active stimulation exactly as they received previously or sham stimulation with rTMS in a double-blind randomized placebo-controlled two-group setup After the extended maintenance phase primary and secondary outcomes questionnaires will be issued and a random subsample of 20 patients 10 per group will go through a third 3-hour-long assessment involving neurophysiological assessment to investigate the changes in connectivity
When 50 of inclusion is completed a preplanned interim futility analysis is scheduled to examine safety and the main outcome
Several strategies currently aim to provide a more individualized strategy for choosing analgesic interventions based on patient-related information In order to allow for the design of efficacy trials in the future the present project is based on a proof-of-concept mechanistic design It will employ rTMS stimulation for pain control but the choice of each of the stimulation targets will be made based on each individuals brain signals as read by EEG recorded before the start of the treatment Therefore before receiving a full rTMS treatment patients will undergo a neurophysiological screening session using single-pulseTMS-EEG Single-pulseTMS and EEG have been routinely used in the clinic as a part of the neurophysiological assessment of patients for decades but have not yet been used in the association as an attempt to try to guide the choice of treatment In the screening session single pulses TMS will be applied to each of the primary network hubs used in therapeutic rTMS M1 DLPFC ACC and PSI Concomitantly the EEG oscillatory activity of these four cortical areas will be recorded and the brain connectivity state will be assessed By using information derived from a patients brain connectivity state using transcranial magnetic stimulation with electroencephalography TMS-EEG the most appropriate of the four classic targets will be selected and used in rTMS on an individualized basis It is hypothesized that the brain regions with low local-to-global connectivity will provide better pain relief compared to non-personalized treatment approaches and compared to targets with optimized local-to-global connectivity status
A total of 90 subjects with chronic pain will be included in a double-blind randomized three parallel-arm study comparing the analgesic effect of the therapeutic rTMS target chosen based on TMS-EEG
1 target area presenting the lowest local-to-global connectivity
2 target area presenting the highest local-to-global connectivity
3 classic M1 stimulation
The subjects will be allocated in a 111 ratio to one of three arms 30 subjects per arm The protocol is designed as an adaptive study incorporating interim analyses after enrolling 30 and 60 subjects These evaluations conducted by a blinded specialist statistician panel will assess the efficacy of the target selection strategy for each arm focusing on the primary outcomes progression
In the initial baseline measurement the subjects will fill out questionnaires and undergo neurophysiological assessments After this baseline measurement the subjects will be assigned to one of the three arms and will receive daily rTMS sessions targeting areas called induction phase for 5 consecutive days Monday to Friday with either high connectivity low connectivity or a classic M1 target Each of the 5 daily stimulations will last 30 minutes of which 15 minutes will be under treatment
The induction phase will be followed by a 6-week maintenance phase with 1 rTMS session per week totaling 6 rTMS sessions At the end of the maintenance phase primary and secondary outcomes questionnaires will be collected to investigate the efficacy of the rTMS treatments A random subsample of 30 participants 10 from each arm will be asked if they would like to participate in a second 3-hour neurophysiological assessment to investigate the changes in brain connectivity
Subjects experiencing significant pain reduction according to the primary outcome by the treatment will be asked if they would like to continue maintenance stimulation sessions Participants accepted to join this part of the study will receive 1 stimulation session every 2 weeks for 4 weeks total of 2 stimulation sessions The participants will receive either active stimulation exactly as they received previously or sham stimulation with rTMS in a double-blind randomized placebo-controlled two-group setup After the extended maintenance phase primary and secondary outcomes questionnaires will be issued and a random subsample of 20 patients 10 per group will go through a third 3-hour-long assessment involving neurophysiological assessment to investigate the changes in connectivity
When 50 of inclusion is completed a preplanned interim futility analysis is scheduled to examine safety and the main outcome
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