Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06395649 |
| Other study ID # |
N-20230076 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 15, 2024 |
| Est. completion date |
December 31, 2028 |
Study information
| Verified date |
May 2024 |
| Source |
Aalborg University |
| Contact |
Enrico De Martino, Dr |
| Phone |
91811183 |
| Email |
edm[@]hst.aau.dk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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
adjusting/personalizing the magnetic stimulations to each individual person.
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 individual's 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 patient´s 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 1:1:1 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 outcome's 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.
