Trial Outcomes & Findings for Noninvasive Peripheral Nerve Stimulation for Medication-Refractory Primary RLS (The RESTFUL Study) (NCT NCT04874155)
NCT ID: NCT04874155
Last Updated: 2024-10-08
Results Overview
Responder rate is defined as the proportion of responses of "Much Improved" or "Very Much Improved" relative to baseline on the investigator-rated 7-point CGI-I scale.
COMPLETED
NA
133 participants
Week 4
2024-10-08
Participant Flow
Subjects must have received a medical diagnosis of primary restless legs syndrome (RLS), have moderate-severe RLS and be refractory to RLS medication.
Participant milestones
| Measure |
TOMAC Group
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver active stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
Sham Control Group
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver SHAM stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
|---|---|---|
|
Overall Study
STARTED
|
68
|
65
|
|
Overall Study
COMPLETED
|
65
|
62
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
Reasons for withdrawal
| Measure |
TOMAC Group
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver active stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
Sham Control Group
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver SHAM stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
Baseline Characteristics
Noninvasive Peripheral Nerve Stimulation for Medication-Refractory Primary RLS (The RESTFUL Study)
Baseline characteristics by cohort
| Measure |
TOMAC Group
n=68 Participants
Noninvasive peripheral nerve stimulation device programmed to deliver active stimulation - Phase 1
NTX100 Neuromodulation System - Active: Noninvasive peripheral nerve stimulation device programmed to active mode.
|
Sham Control Group
n=65 Participants
Noninvasive peripheral nerve stimulation device programmed to deliver non-therapeutic (sham) stimulation - Phase 1
NTX100 Neuromodulation System - Sham: Noninvasive peripheral nerve stimulation device programmed to sham mode.
|
Total
n=133 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
64 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
125 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
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 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
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
64 Participants
n=5 Participants
|
65 Participants
n=7 Participants
|
129 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
|
IRLS Total Score at Baseline
|
25.2 Units on a scale
STANDARD_DEVIATION 5.3 • n=5 Participants
|
25.4 Units on a scale
STANDARD_DEVIATION 5.3 • n=7 Participants
|
25.3 Units on a scale
STANDARD_DEVIATION 5.3 • n=5 Participants
|
|
Age, Customized
|
56.3 years
STANDARD_DEVIATION 10.96 • n=5 Participants
|
58.6 years
STANDARD_DEVIATION 11.81 • n=7 Participants
|
57.46 years
STANDARD_DEVIATION 11.39 • n=5 Participants
|
|
Sex: Female, Male
Female
|
39 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
80 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 4Population: Primary Efficacy Endpoint (CGI-I Responder Rate at Week 4) - (ITT Population)
Responder rate is defined as the proportion of responses of "Much Improved" or "Very Much Improved" relative to baseline on the investigator-rated 7-point CGI-I scale.
Outcome measures
| Measure |
TOMAC Group
n=68 Participants
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver active stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
Sham Control Group
n=65 Participants
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver SHAM stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
|---|---|---|
|
Number of Subjects for Which the Clinician Reported "Much Improved" or "Very Much Improved" on the Clinical Global Impressions-Improvement (CGI-I) Scale for TOMAC Compared to Sham
|
29 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: Week 4Population: Key Secondary Efficacy Endpoints (ITT Population)
Responder rate is defined as the proportion of responses of "Much Improved" or "Very Much Improved" relative to baseline on the participant-rated 7-point PGI-I scale.
Outcome measures
| Measure |
TOMAC Group
n=68 Participants
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver active stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
Sham Control Group
n=65 Participants
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver SHAM stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
|---|---|---|
|
Responder Rate on Patient Global Impressions-Improvement (PGI-I) Scale
|
33 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Week 4Population: Key Secondary Efficacy Endpoints (ITT Population)
IRLS is a participant-rated questionnaire that rates RLS severity from 0-40, where 40 is the most severe.
Outcome measures
| Measure |
TOMAC Group
n=68 Participants
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver active stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
Sham Control Group
n=65 Participants
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver SHAM stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
|---|---|---|
|
Mean Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score
|
-7.2 score on a scale
Standard Deviation 6.2
|
-3.8 score on a scale
Standard Deviation 5.9
|
SECONDARY outcome
Timeframe: Week 4Population: Key Secondary Efficacy Endpoints (ITT Population)
MOS-II is a subscale of the participant-rated MOS questionnaire that measures subjective sleep quality. The MOS-I (6-items) and MOS-II (9-items) are the two validated subscales of the 12-item MOS Sleep Scale. Both are scored from 0 to 100, where 100 corresponds to the worst possible sleep problems and 0 corresponds to no sleep problems. See https://labs.dgsom.ucla.edu/hays/files/view/docs/surveys/sleep/sleepman-112603.pdf for more information.
Outcome measures
| Measure |
TOMAC Group
n=68 Participants
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver active stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
Sham Control Group
n=65 Participants
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver SHAM stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
|---|---|---|
|
Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index II (MOS-II) Score
|
-13.7 score on a scale
Standard Deviation 14.9
|
-4.0 score on a scale
Standard Deviation 14.8
|
SECONDARY outcome
Timeframe: Week 4MOS-I is a subscale of the participant-rated MOS questionnaire that measures subjective sleep quality. The MOS-I (6-items) and MOS-II (9-items) are the two validated subscales of the 12-item MOS Sleep Scale. Both are scored from 0 to 100, where 100 corresponds to the worst possible sleep problems and 0 corresponds to no sleep problems. See https://labs.dgsom.ucla.edu/hays/files/view/docs/surveys/sleep/sleepman-112603.pdf for more information.
Outcome measures
| Measure |
TOMAC Group
n=68 Participants
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver active stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
Sham Control Group
n=65 Participants
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver SHAM stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
|---|---|---|
|
Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index I (MOS-I) Score
|
-11.8 score on a scale
Standard Deviation 14.7
|
-2.8 score on a scale
Standard Deviation 14.9
|
SECONDARY outcome
Timeframe: Week 4Mean rating on the investigator-rated 7-point Likert CGI-I scale, where lower scores indicate improvement. Possible choices (followed by scale value) are: Very much improved (1), Much improved (2), Minimally improved (3), No change (4), Minimally worse (5), Much worse (6), Very Much Worse (7).
Outcome measures
| Measure |
TOMAC Group
n=68 Participants
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver active stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
Sham Control Group
n=65 Participants
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver SHAM stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
|---|---|---|
|
Mean Clinical Global Impressions-Improvement (CGI-I) Scale Rating
|
2.6 score on a scale
Standard Deviation 1.1
|
3.5 score on a scale
Standard Deviation 0.9
|
SECONDARY outcome
Timeframe: Week 8Population: Key Secondary Efficacy Endpoints (ITT Population)
Question #7 of the IRLS assesses the participant-rated frequency (days/week) of RLS symptoms on a scale from 0 to 4, where lower scores indicate less frequent symptoms
Outcome measures
| Measure |
TOMAC Group
n=68 Participants
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver active stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
Sham Control Group
n=65 Participants
Stage 1 (4 weeks): Double-blind, Noninvasive peripheral nerve stimulation device programmed to deliver SHAM stimulation
Stage 2 (4 weeks): Open-label, noninvasive peripheral nerve stimulation device programmed to active mode.
|
|---|---|---|
|
Score for Question #7 of the International Restless Legs Syndrome Study Group Rating Scale (IRLS)
|
-0.9 Days per Week
Standard Deviation 1.07
|
-0.6 Days per Week
Standard Deviation 1.2
|
Adverse Events
TOMAC Group
Sham Control Group
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
TOMAC Group
n=68 participants at risk
Treatment group
|
Sham Control Group
n=65 participants at risk
Control group
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Administration site discomfort
|
32.4%
22/68 • Number of events 22 • 8 weeks
Descriptive analyses of adverse events for both study arms, classified and tabulated by seriousness, relationship to the device, and severity.
|
24.6%
16/65 • Number of events 16 • 8 weeks
Descriptive analyses of adverse events for both study arms, classified and tabulated by seriousness, relationship to the device, and severity.
|
|
Skin and subcutaneous tissue disorders
Administration site irritation
|
8.8%
6/68 • Number of events 6 • 8 weeks
Descriptive analyses of adverse events for both study arms, classified and tabulated by seriousness, relationship to the device, and severity.
|
10.8%
7/65 • Number of events 7 • 8 weeks
Descriptive analyses of adverse events for both study arms, classified and tabulated by seriousness, relationship to the device, and severity.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place