Restless Legs Syndrome
Conditions
Brief summary
Multi-center, prospective open-label extension study of noninvasive peripheral nerve stimulation (NPNS) with the NTX100 Neuromodulation System for patients with medication-refractory moderate- severe primary RLS
Detailed description
This is an extension study only inviting subjects who have previously completed the RESTFUL Study (NCT04874155). Each study subject is enrolled into one of the following Arms: Arm 1 (Direct Roll-Over Extension): 24-week open-label NPNS followed by 8-weeks of no treatment, no delay after completion of the RESTFUL Study Arm 2 (Control Group): 24-weeks of no treatment
Interventions
DEVICENTX100 Neuromodulation System
Active Noninvasive peripheral nerve stimulation device programmed to active mode
Sponsors
Noctrix Health, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
22 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Subject previously completed the RESTFUL Study (NCT04874155). 2. Subject has signed a valid, Institutional Review Board-approved informed consent form, can understand the requirements of the study and instructions for device usage, and can converse in English. 3. \[applicable to Arm 1 only\] Subject agrees to not change dosage or schedule of any medications that are known to impact RLS symptoms during the study, including RLS medications, antidepressants, sleep medications, or sedative antihistamines.
Exclusion criteria
1. \[applicable to Arm 1 only\] Subject has active medical device implant anywhere in the body (including but not limited to pacemakers, spinal cord stimulators, deep brain stimulators) or metal implant at the site of study device electrode application. 2. \[applicable to Arm 1 only\] Subject has been diagnosed with one of the following conditions: * Epilepsy or other seizure disorder Current, active or acute or chronic infection other than common cold \[and except for acute infections with mild symptoms\] * A malignancy within the past 5 years (not including basal or squamous cell skin cancer) * Stage 4-5 chronic kidney disease or renal failure * Severe movement disorder symptoms (Parkinson's disease, Huntington's disease, dyskinesia, dystonia) * Deep vein thrombosis * Multiple sclerosis 3. Subject has moderate or severe cognitive disorder or mental illness. 4. \[applicable to Arm 1 only\] Subject has known allergy to device materials, electrode gel, polyurethane foam, or lycra (or severe previous reaction to medical adhesives or bandages). 5. \[applicable to Arm 1 only\] Subject has severe edema affecting lower legs. 6. \[applicable to Arm 1 only\] Subject has any of the following at or near the location of device application. * Acute injury * Cellulitis * Open sores * Other skin condition 7. \[applicable to Arm 1 only\] Subject is on dialysis or anticipated to start dialysis while participating in the study. 8. \[applicable to Arm 1 only\] Subject has received another investigational device or drug within 30 days before study entry, is planning to receive another investigational device or drug during the study, or is planning to change RLS medications during the study. 9. Subject is unable or unwilling to comply with study requirements. 10. \[applicable to Arm 1 only\] Subject is pregnant or trying to become pregnant. 11. Subject has a medical condition not listed above that may affect validity of the study as determined by the investigator. 12. \[applicable to Arm 1 only\] Subject has a medical condition not listed above that may put the subject at risk as determined by the investigator. 13. Subject was unwilling or unable to follow instructions in the RESTFUL Study, including missing 2 or more follow-up evaluations. 14. \[applicable to Arm 1 only\] Subject failed to properly operate the investigational devices during Weeks 5-8 of the RESTFUL Study. 15. \[applicable to Arm 1 only\] Subject experienced a significantly higher than expected rate of device malfunctions in the RESTFUL Study, such that the malfunctions appeared to be directly related to the subject's pattern of use.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects for Which the Clinician Reported Much Improved or Very Much Improved on the Clinical Global Impressions-Improvement (CGI-I) Scale in Treatment Group (Arm 1) Relative to Baseline. | Week 24 | 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. The outcomes were also evaluated as Treatment Group (Arm 1) at 24 weeks related to Control Group (Arm 2) at 24 weeks. The primary outcome, however, is the measure relative to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects That Report Much Improved or Very Much Improved on the Patient Global Impressions-Improvement (PGI-I) Scale in the Treatment Group (Arm 1) Relative to Baseline. | Week 24 | Responder rate is defined as the proportion of responses Much Improved or Very Much Improved on the Patient Global Impressions-Improvement (PGI-I) Scale in the Treatment Group (Arm 1) Relative to Baseline. Note that the Responder Rate was be calculated relative to baseline for the endpoint but was also be calculated relative to the value for the control group at Week 24. |
| Mean Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score in Arm 1 | Week 24 | IRLS is a participant-rated questionnaire that rates RLS severity from 0-40, where 40 is the most severe. Note that the IRLS score was calculated relative to baseline for the endpoint but was also be calculated relative to the value for the control group at Week 24. |
| Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index II (MOS-II) Score in Arm 1 | Week 24 | 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. Note that the mean MOS-II score was calculated relative to baseline for the endpoint but was also be calculated relative to the value for the control group at Week 24. |
| Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index I (MOS-I) Score in Arm 1 | Week 24 | MOS-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. Note that the outcome is measured relative to baseline but also relative to the Arm 2 (control group) at 24 weeks. |
| Days Per Week of RLS Symptoms Based on Question #7 in the International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score in Arm 1 | Week 24 | The International Restless Legs Syndrome (IRLS) Question #7 is a participant-rated question that measures the frequency of RLS symptoms in terms of days per week. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the parent study (CT-04, RESTFUL Study). The CT-04 study enrolled 133 subjects, 126 of which completed the study. These 126 subjects were invited to participate in the CT-05 Extension study but 23 were not enrolled (7 not reachable, 12 did not consent, 1 was ineligible and 3 were unable to enroll due to a site not yet active.). This left 103 subjects that were consented and enrolled in CT-05, the Extension study.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 - Direct Roll-Over Extension 24-wks of Active neurostimulation - Noninvasive peripheral nerve stimulation device programmed to deliver active stimulation; followed by 8-wks of No Intervention
NTX100 Neuromodulation System: Active Noninvasive peripheral nerve stimulation device programmed to active mode | 44 |
| Arm 2 - Control Group 24-wks of No Intervention | 59 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Arm 2 - Control Group | Total | Arm 1 - Direct Roll-Over Extension |
|---|---|---|---|
| Age, Continuous | 57.5 years STANDARD_DEVIATION 11.85 | 57.6 years STANDARD_DEVIATION 11.75 | 57.7 years STANDARD_DEVIATION 11.65 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 7 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 92 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 52 Participants | 92 Participants | 40 Participants |
| Sex: Female, Male Female | 32 Participants | 58 Participants | 26 Participants |
| Sex: Female, Male Male | 27 Participants | 45 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 44 |
| other Total, other adverse events | 10 / 44 | 3 / 44 |
| serious Total, serious adverse events | 0 / 44 | 0 / 44 |
Outcome results
Primary
Number of Subjects for Which the Clinician Reported Much Improved or Very Much Improved on the Clinical Global Impressions-Improvement (CGI-I) Scale in Treatment Group (Arm 1) Relative to Baseline.
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. The outcomes were also evaluated as Treatment Group (Arm 1) at 24 weeks related to Control Group (Arm 2) at 24 weeks. The primary outcome, however, is the measure relative to baseline.
Time frame: Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 - Direct Roll-Over Extension | Number of Subjects for Which the Clinician Reported Much Improved or Very Much Improved on the Clinical Global Impressions-Improvement (CGI-I) Scale in Treatment Group (Arm 1) Relative to Baseline. | 32 Participants |
| Arm 2 - Control Group | Number of Subjects for Which the Clinician Reported Much Improved or Very Much Improved on the Clinical Global Impressions-Improvement (CGI-I) Scale in Treatment Group (Arm 1) Relative to Baseline. | 8 Participants |
Secondary
Days Per Week of RLS Symptoms Based on Question #7 in the International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score in Arm 1
The International Restless Legs Syndrome (IRLS) Question #7 is a participant-rated question that measures the frequency of RLS symptoms in terms of days per week.
Time frame: Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Direct Roll-Over Extension | Days Per Week of RLS Symptoms Based on Question #7 in the International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score in Arm 1 | -1.50 Days/Week | Standard Deviation 1.34 |
| Arm 2 - Control Group | Days Per Week of RLS Symptoms Based on Question #7 in the International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score in Arm 1 | -0.41 Days/Week | Standard Deviation 0.91 |
Secondary
Mean Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score in Arm 1
IRLS is a participant-rated questionnaire that rates RLS severity from 0-40, where 40 is the most severe. Note that the IRLS score was calculated relative to baseline for the endpoint but was also be calculated relative to the value for the control group at Week 24.
Time frame: Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Direct Roll-Over Extension | Mean Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score in Arm 1 | -11.3 score on a scale | Standard Deviation 8.43 |
| Arm 2 - Control Group | Mean Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score in Arm 1 | -5.4 score on a scale | Standard Deviation 6.7 |
Secondary
Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index II (MOS-II) Score in Arm 1
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. Note that the mean MOS-II score was calculated relative to baseline for the endpoint but was also be calculated relative to the value for the control group at Week 24.
Time frame: Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Direct Roll-Over Extension | Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index II (MOS-II) Score in Arm 1 | -17.2 score on a scale | Standard Deviation 18.81 |
| Arm 2 - Control Group | Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index II (MOS-II) Score in Arm 1 | -6.4 score on a scale | Standard Deviation 15.18 |
Secondary
Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index I (MOS-I) Score in Arm 1
MOS-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. Note that the outcome is measured relative to baseline but also relative to the Arm 2 (control group) at 24 weeks.
Time frame: Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Direct Roll-Over Extension | Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index I (MOS-I) Score in Arm 1 | -15.8 score on a scale | Standard Deviation 19.21 |
| Arm 2 - Control Group | Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index I (MOS-I) Score in Arm 1 | -5.7 score on a scale | Standard Deviation 15.48 |
Secondary
Number of Subjects That Report Much Improved or Very Much Improved on the Patient Global Impressions-Improvement (PGI-I) Scale in the Treatment Group (Arm 1) Relative to Baseline.
Responder rate is defined as the proportion of responses Much Improved or Very Much Improved on the Patient Global Impressions-Improvement (PGI-I) Scale in the Treatment Group (Arm 1) Relative to Baseline. Note that the Responder Rate was be calculated relative to baseline for the endpoint but was also be calculated relative to the value for the control group at Week 24.
Time frame: Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 - Direct Roll-Over Extension | Number of Subjects That Report Much Improved or Very Much Improved on the Patient Global Impressions-Improvement (PGI-I) Scale in the Treatment Group (Arm 1) Relative to Baseline. | 33 Participants |
| Arm 2 - Control Group | Number of Subjects That Report Much Improved or Very Much Improved on the Patient Global Impressions-Improvement (PGI-I) Scale in the Treatment Group (Arm 1) Relative to Baseline. | 12 Participants |