Clinical Trial Details
— Status: Terminated
Administrative data
NCT number |
NCT05625386 |
Other study ID # |
AHMU-TMS-FOG-twotargets |
Secondary ID |
|
Status |
Terminated |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
December 22, 2022 |
Est. completion date |
March 31, 2024 |
Study information
Verified date |
April 2024 |
Source |
Anhui Medical University |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
The aim of the current study was to verify whether high-dose TMS treatment of the motor and
cognitive cortices is more effective in alleviating FOG than conventional-dose TMS of the
motor cortex only. Specifically, investigator hypothesized that the effect of dual-target TMS
on FOG is better than traditional stimulation of the motor cortex only, and the effect of
high-dose TMS is better than conventional doses.
Description:
This was an open-label, randomized controlled study. Participants were randomized in a 1:1:1
fashion to receive dual-target, high-dose TMS (DHT), dual-target, conventional-dose TMS
(DCT), and single-target, conventional-dose TMS (SCT). SCT was designated as the control
group with protocol reference to evidence-based guidelines, while DHT and DCT served as the
experimental groups.
DHT refers to the left primary motor cortex of the lower leg (M1) and dorsolateral prefrontal
cortex (DLPFC) receiving 9000 pulses/day of intermittent TBS (iTBS) for 5 consecutive days.
DCT refers to the left M1 and DLPFC receiving 1800 pulses/day of iTBS for 5 consecutive days.
The order of stimulation for the two targets was randomized across participants and the order
of stimulation within participants remained unchanged throughout the session. SCT refers to
the left M1 receiving 1800 pulses/day of iTBS treatment for 5 consecutive days.
Motor and cognitive measures were performed ("on medication" state) 1 day before TMS
(baseline), 1 day after completion of TMS (post), and 1 month after completion of TMS
(follow-up). The primary outcome of this study was the change in FOGQ scores from baseline to
follow-up. Secondary outcomes included changes in the Unified Parkinson's Disease Rating
Scale Part III (UPDRS III), 5 m Timed Up-and-Go test (TUG), FOG-provoking test
(Standing-Start 180° Turn Test, SS-180), Stroop color-naming (SCN), Stroop word-reading
(SWR), Stroop color-word (SCW), and Color Trails Test interference index (CTTII) from
baseline to follow-up.
TMS was performed using a Magstim Rapid2 transcranial magnetic stimulator (Magstim Company,
Whitland, UK) with a 70-mm air-cooled figure-of-eight coil. All stimulations were guided by
the participant's anatomical image (1 × 1 × 1 mm3) and a frameless neuronavigation system
(Brainsight; Rogue Research, Montreal, QC, Canada).
Stimulation intensity: Because each participant had different sensitivity to TMS, the
individual Resting Motor Threshold (RMT) was measured before intervention. Specifically,
surface electrodes (Ag/AgCl) were attached to both ends of the right abductor pollicis muscle
(the ground wire was connected to the ulnar styloid process) and the left finger motor cortex
was stimulated one time. The motor-evoked potentials were recorded from the hand muscles. The
RMT was considered when the evoked potential > 50 μV occurred in > 5 of 10 consecutive
stimulations. The stimulation intensity during intervention was 80% of the RMT in the current
study.
Stimulation sequence: Each iTBS sequence in the high-dose stimulation sequence released 900
pulses at a time with a pulse cluster repeated every 200 ms at a frequency of 5 Hz. Each
pulse cluster contained three pulses with a frequency of 50 Hz, stimulation time of 2 s, and
interval of 8 s. A total of 10 iTBS sessions was performed each day with an interval of 40
min and the daily stimulation dose was 9000 pulses. Each iTBS sequence in the
conventional-dose stimulation sequence released 600 pulses at a time with a pulse cluster
repeated every 200 ms at a frequency of 5 Hz. Each pulse cluster contained three pulses with
a frequency of 50 Hz, stimulation time of 2 s, and interval of 8 s. A total of three iTBS
sessions were performed each day with an interval of 40 min and the daily stimulation dose
was 1800 pulses.
Stimulation targets: There were two stimulation targets in this study that were used to
intervene in the motor and cognitive cortices. The stimulation target of the motor cortex is
located in the lower leg of the left primary motor cortex in the Montreal Neurological
Institute space (coordinates: -10, -24, 75 [https:/ /afni.nimh.nih.gov/MNI_Atlas]) based on
structural MRI. The stimulation target of the cognitive cortex was the left dorsolateral
prefrontal cortex, which has the strongest functional connectivity with the executive control
network (see Supplementary materials), based on fMRI. Finally, targets were transformed into
the native space for each participant by applying an inverse matrix produced during brain
structure and function segmentation using SPM12 (www.fil.ion.ucl.ac.uk/spm) and TMStarget
software.