Trial Outcomes & Findings for Median Nerve Stimulation Pilot (NCT NCT04731714)

Results Overview

The number of tics per minute is assessed by an expert rater blind to condition and time point. Mean tic frequency was compared in on vs. off 1-minute stimulation epochs on the rhythmic MNS day. This analysis replicates that of Study 3 in the Morera Maiquez et al 2020 citation, who reported tics in the last 40 seconds of the block to minimize carryover effects. A Mixed Models Analysis was used to test statistical significance; it included a factor for possible within-day carryover effect and used a logarithmic transformation for tic count. Data reported here have been back-transformed to the number of tics in the last 40 s of the stimulation blocks.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

34 participants

Primary outcome timeframe

During the 1-minute on and 1-minute off blocks of rhythmic MNS stimulation (total 4 blocks)

Results posted on

2023-10-05

Participant Flow

Participants were recruited through clinical referrals, referrals from the University of Nottingham research team, advertising and word of mouth. Recruitment began in June, 2021, with the first subject enrolled in July, 2021. Study completion was in April, 2022.

2 potential participants did not meet study inclusion criteria at screening and therefore were excluded prior to study arm assignment.

Participant milestones

Participant milestones
Measure	Experimental: Rhythmic MNS, Then Arrhythmic MNS Participants will complete two stimulation sessions, at least a week apart. The first session involves rhythmic MNS and the second uses arrhythmic MNS. Rhythmic median nerve stimulation: Square-wave 200 µs pulses triggered by computer at 12 Hz, at the threshold for thumb movement (expected \~2-15mA), applied to surface electrodes over the median nerve at the right wrist (conductive gel, 30 mm apart center-to-center, anode distal). This is a non-significant risk device study. Arrhythmic median nerve stimulation: Square-wave 200 µs pulses triggered by computer at random intervals with a mean rate of 12 Hz (as described in Morera Maiquez et al., 2020), at the threshold for thumb movement (expected \~2-15mA), applied to surface electrodes over the median nerve at the right wrist (conductive gel, 30 mm apart center-to-center, anode distal). This is a non-significant risk device study.	Experimental: Arrhythmic MNS, Then Rhythmic MNS Participants will complete two stimulation sessions, at least a week apart. The first session involves arrhythmic MNS and the second uses rhythmic MNS. Rhythmic median nerve stimulation: Square-wave 200 µs pulses triggered by computer at 12 Hz, at the threshold for thumb movement (expected \~2-15mA), applied to surface electrodes over the median nerve at the right wrist (conductive gel, 30 mm apart center-to-center, anode distal). This is a non-significant risk device study. Arrhythmic median nerve stimulation: Square-wave 200 µs pulses triggered by computer at random intervals with a mean rate of 12 Hz (as described in Morera Maiquez et al., 2020), at the threshold for thumb movement (expected \~2-15mA), applied to surface electrodes over the median nerve at the right wrist (conductive gel, 30 mm apart center-to-center, anode distal). This is a non-significant risk device study.
Overall Study STARTED	16	16
Overall Study Completed Study Visit 1	16	16
Overall Study Completed Study Visit 2	16	16
Overall Study COMPLETED	16	16
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Median Nerve Stimulation Pilot

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental: Rhythmic MNS, Then Arrhythmic MNS n=16 Participants Participants will complete two stimulation sessions, at least a week apart. The first session involves rhythmic MNS and the second uses arrhythmic MNS. Rhythmic median nerve stimulation: Square-wave 200 µs pulses triggered by computer at 12 Hz, at the threshold for thumb movement (expected \~2-15mA), applied to surface electrodes over the median nerve at the right wrist (conductive gel, 30 mm apart center-to-center, anode distal). This is a non-significant risk device study. Arrhythmic median nerve stimulation: Square-wave 200 µs pulses triggered by computer at random intervals with a mean rate of 12 Hz (as described in Morera Maiquez et al., 2020), at the threshold for thumb movement (expected \~2-15mA), applied to surface electrodes over the median nerve at the right wrist (conductive gel, 30 mm apart center-to-center, anode distal). This is a non-significant risk device study.	Experimental: Arrhythmic MNS, Then Rhythmic MNS n=16 Participants Participants will complete two stimulation sessions, at least a week apart. The first session involves arrhythmic MNS and the second uses rhythmic MNS. Rhythmic median nerve stimulation: Square-wave 200 µs pulses triggered by computer at 12 Hz, at the threshold for thumb movement (expected \~2-15mA), applied to surface electrodes over the median nerve at the right wrist (conductive gel, 30 mm apart center-to-center, anode distal). This is a non-significant risk device study. Arrhythmic median nerve stimulation: Square-wave 200 µs pulses triggered by computer at random intervals with a mean rate of 12 Hz (as described in Morera Maiquez et al., 2020), at the threshold for thumb movement (expected \~2-15mA), applied to surface electrodes over the median nerve at the right wrist (conductive gel, 30 mm apart center-to-center, anode distal). This is a non-significant risk device study.	Total n=32 Participants Total of all reporting groups
Age, Continuous	36.81 years STANDARD_DEVIATION 16.81 • n=5 Participants	31.25 years STANDARD_DEVIATION 16.16 • n=7 Participants	34.03 years STANDARD_DEVIATION 16.51 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	9 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	16 participants n=5 Participants	16 participants n=7 Participants	32 participants n=5 Participants

PRIMARY outcome

Timeframe: During the 1-minute on and 1-minute off blocks of rhythmic MNS stimulation (total 4 blocks)

Population: All participants in the study, 4 blocks for each participant (2 on, 2 off, in random order)

The number of tics per minute is assessed by an expert rater blind to condition and time point. Mean tic frequency was compared in on vs. off 1-minute stimulation epochs on the rhythmic MNS day. This analysis replicates that of Study 3 in the Morera Maiquez et al 2020 citation, who reported tics in the last 40 seconds of the block to minimize carryover effects. A Mixed Models Analysis was used to test statistical significance; it included a factor for possible within-day carryover effect and used a logarithmic transformation for tic count. Data reported here have been back-transformed to the number of tics in the last 40 s of the stimulation blocks.

Outcome measures

Outcome measures
Measure	All Participants n=32 Participants All participants in the study, including both those assigned to "sequence: rhythmic-arrhythmic" and those assigned to "sequence: arrhythmic-rhythmic"
Change in Tic Frequency From When MNS is Turned Off Stimulation Off	12.1 Tic frequency (number of tics in 40 s) Interval 9.3 to 15.8
Change in Tic Frequency From When MNS is Turned Off Stimulation On	8.9 Tic frequency (number of tics in 40 s) Interval 6.6 to 11.8

PRIMARY outcome

Timeframe: During the 1-minute on and 1-minute off blocks of rhythmic MNS stimulation (total 4 blocks)

Population: All participants in the study, 4 blocks for each participant (2 on, 2 off, in random order)

Severity is rated on a 5-point scale for each occurrence of any tic. The scale is the Intensity item from the Yale Global Tic Severity Scale \[YGTSS\], which uses integer scores from 0 (no tics) to 5 (severe intensity). Mean tic severity was compared in on vs. off 1-minute stimulation epochs on the rhythmic MNS day. This analysis replicates that of Study 3 in the Morera Maiquez et al 2020 citation.