Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT03658694 |
Other study ID # |
RGDCA03 |
Secondary ID |
|
Status |
Completed |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
April 1, 2019 |
Est. completion date |
March 1, 2023 |
Study information
Verified date |
October 2023 |
Source |
University of Sao Paulo |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
There are currently several points concerning rTMS for pain relief that have a huge impact in
the practical application of rTMS in clinical practice, but which have not been approached by
previous studies. Also, an even more important issue is the frequency of the sessions in each
treatment protocol. The idea of performing stimulation in chronic pain patients on a
consecutive daily basis for long-term treatments seem unrealistic and potentially costly.
However, it has been reported in animals, healthy subjects and FM patients that the analgesic
effects of rTMS can outlast the stimulation session for several minutes and even days. This
has led to the proposal that pain treatment with rTMS could be performed in consecutive daily
induction sessions, followed by spaced (weekly, fortnightly and even monthly) maintenance
sessions. This approach is similar to what is performed routinely in patients with major
depression treated by rTMS to the dorsolateral prefrontal cortex, and has successfully been
tested in FM patients in a single- center study. Should this approach prove effective in
larger prospective multicentric studies, rTMS could enter the armamentarium of non-invasive,
non- pharmacological, low-adverse event therapeutic options to relieve fibromyalgia- related
pain and associate symptoms. Hence, our aim is to conduct a multicentric international
clinical trial on the influence of rTMS in the control of pain in a consecutive adaptive
trial design where conventional rTMS (10Hz) and patterned rTMS (theta-burst) will be studied.
Stimulations will be performed in a clinical practice-friendly approach, where daily
maintenance sessions will be followed by weekly, and fortnightly stimulation sessions. There
have been very scarce adaptive trials in the pain and non-invasive stimulation fields. This
methodological approach allows for the use of lower number of patients in consecutive trials
and, among other qualities, it allows for the imputation of data from the first trial into
the second one, thus decreasing the duration of the studies and the number of participants.
Description:
There are currently several points concerning rTMS for pain relief that have a huge impact in
the practical application of rTMS in clinical practice, but which have not been approached by
previous studies. One of them refers to dosing of the treatment. rTMS sessions have been
proposed to comprise from 1000 to 3000 pulses of stimulation in each session, which means
that treatment sessions may last from 7 to 20 minutes. While there are positive studies
reporting different numbers of pulses, the actual stimulation protocol chosen may impact not
only the efficacy of the treatment, but also the duration of the stimulation session, the
time patients stay at the health-care facility, and, thus, cost and compliance to treatment.
Also, an even more important issue is the frequency of the sessions in each treatment
protocol. The idea of performing stimulation in chronic pain patients on a consecutive daily
basis for long-term treatments seem unrealistic and potentially costly. However, it has been
reported in animals, healthy subjects and FM patients that the analgesic effects of rTMS can
outlast the stimulation session for several minutes and even days. This has led to the
proposal that pain treatment with rTMS could be performed in consecutive daily induction
sessions, followed by spaced (weekly, fortnightly and even monthly) maintenance sessions.
This approach is similar to what is performed routinely in patients with major depression
treated by rTMS to the dorsolateral prefrontal cortex, and has successfully been tested in FM
patients in a single- center study. Should this approach prove effective in larger
prospective multicentric studies, rTMS could enter the armamentarium of non-invasive, non-
pharmacological, low-adverse event therapeutic options to relieve fibromyalgia- related pain
and associate symptoms. Hence, our aim is to conduct a multicentric international clinical
trial on the influence of rTMS in the control of pain in a consecutive adaptive trial design
where conventional rTMS and patterned rTMS will be studied. Stimulations will be performed in
a clinical practice-friendly approach, where daily maintenance sessions will be followed by
weekly, and fortnightly stimulation sessions. There have been very scarce adaptive trials in
the pain and non-invasive stimulation fields. This methodological approach allows for the use
of lower number of patients in consecutive trials and, among other qualities, it allows for
the imputation of data from the first trial into the second one, thus decreasing the duration
of the studies and the number of participants. Similarly, this technical approach allows for
pre-planned interim analyses to be performed during data collection, allowing for the sample
size to be readjusted during the trial, and, more importantly, allowing for trial termination
due to futility or due to achievement of the primary endpoint before the end of the original
preplanned data collection period, with lower risk of bias. Here, the adaptive approach will
allow one not only to compare conventional rTMS (10Hz) to sham stimulation, but also, on
second consecutive study, it will provide the first head-to-head study on rTMS to date
comparing the analgesic effects of conventional (10Hz) and patterned (theta-burst) rTMS .