NCT04698343

Noninvasive Peripheral Nerve Stimulation for Restless Legs Syndrome During Opioid Medication Reduction

Completed NA Results posted Last updated 19 September 2024

What this trial tests

NA trial testing Noninvasive Peripheral Nerve Stimulation (NPNS) in Restless Legs Syndrome in 21 participants. Completed in 28 March 2023.

Timeline

6 April 2021

Primary endpoint
27 February 2023

28 March 2023

Quick facts

Lead sponsor	Noctrix Health, Inc.
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	21
Start date	6 April 2021
Primary completion	27 February 2023
Estimated completion	28 March 2023
Sites	2 locations across United States

Drugs / interventions tested

• Noninvasive Peripheral Nerve Stimulation (NPNS)

Conditions studied

• Restless Legs Syndrome — all drugs for Restless Legs Syndrome →

Sponsor

Noctrix Health, Inc.

Who can join

Adults 18 to 89, any sex, with Restless Legs Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Subjects Without a Clinically Significant Increase in RLS Symptoms During the First Phase Involving an Opioid Dose Reduction of >= 20% Relative to Baseline. Primary · Week 1

Percentage of subjects without a clinically significant increase in RLS symptoms during the first Phase involving an opioid dose reduction of \>= 20% relative to baseline. The clinically significant increase was assessed by determining the Clinician Global Impression of Improvement (CGI-I) score for the subject. 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). Scores of 6 or 7 would be considered a clinically significant increase in RLS Symptoms.

Group	Value	95% CI
Noninvasive Peripheral Nerve Stimulation (NPNS)	14

Percentage of Subjects Without a Clinically Significant Increase in RLS Symptoms During the First Phase Involving an Opioid Dose Reduction of >= 1/3 Relative to Baseline. Secondary · 1 week

Percentage of subjects without a clinically significant increase in RLS symptoms during the first Phase involving an opioid dose reduction of \>= 1/3 relative to baseline. The clinically significant increase was assessed by determining the Clinician Global Impression of Improvement (CGI-I) score for the subject. 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). Scores of 6 or 7 would be considered a clinically significant increase in RLS Symptoms.

Group	Value	95% CI
Noninvasive Peripheral Nerve Stimulation (NPNS)	8

Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score During Step-down #1 With an Opioid Dose Reduction of >=20% Secondary · 1 week

IRLS is a participant-rated questionnaire that rates RLS severity from 0-40, where 40 is the most severe.

Group	Value	95% CI
Noninvasive Peripheral Nerve Stimulation (NPNS)	5.8	± 6.1

Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score During Step-down #2 With an Opioid Dose Reduction of >=1/3 Secondary · 1 week into Step-down #2

IRLS is a participant-rated questionnaire that rates RLS severity from 0-40, where 40 is the most severe.

Group	Value	95% CI
Noninvasive Peripheral Nerve Stimulation (NPNS)	5.7	± 6.9

Maximum Percent Change in Opioid Dose Relative to Baseline Without a Clinically Significant Increase in RLS Symptoms. Secondary · 1 week into final step-down

The clinically significant increase was assessed by determining the Clinician Global Impression of Improvement (CGI-I) score for the subject. 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). Scores of 6 or 7 would be considered a clinically significant increase in RLS Symptoms.

Group	Value	95% CI
Noninvasive Peripheral Nerve Stimulation (NPNS)	29.9	± 23.7

NPNS Tolerability Rate - Percentage of Subjects Who Withdrew From Optional Phase 3 Citing Lack of Tolerability of NPNS as the Primary Reason for Withdrawal. Secondary · Up to 9 weeks

Percentage of subjects who withdraw from study prior to the optional Phase 3 citing lack of tolerability of NPNS as the primary reason for withdrawal. The criterion for success was fewer than 20% of subjects who begin NPNS treatment withdrawing for this reason.

Group	Value	95% CI
Noninvasive Peripheral Nerve Stimulation (NPNS)	0

Percentage of Grade 2 or Higher NPNS-related Adverse Events. Secondary · Up to 9 weeks

A Grade 2 adverse event is described as: moderate; minimal, local, or non-invasive intervention indicated; limiting age appropriate instrumental Activities of Daily Living such as preparing meals, shopping for groceries or clothes, using the telephone, and managing money. The success criteria was fewer than 20% Grade 2 or higher NPNS-related adverse events. (Definition from the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 NCI, NIH, US Department of Health and Human Services (DHHS). May 29, 2009 NIH publication #- 09-7473.)

Group	Value	95% CI
Noninvasive Peripheral Nerve Stimulation (NPNS)	0

Percentage of Grade 3 or Higher NPNS-related Adverse Events. Secondary · Up to 9 weeks

The criteria for success were no Grade 3 or higher NPNS-related adverse events. A Grade 3 adverse event was described as: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care Activities of Daily Living such as bathing, dressing and undressing, feeding oneself, using the toilet, taking medications, and not being bedridden. (Definition from the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 NCI, NIH, DHHS. May 29, 2009 NIH publication #- 09-7473.)

Group	Value	95% CI
Noninvasive Peripheral Nerve Stimulation (NPNS)	0

NPNS Adherence Ratio During Step-down #1 and Step-down #2. Secondary · 1 week post step-down

NPNS adherence was based on the percent of device usage on nights with RLS symptoms during Assessment periods. Adherence was assessed during assessment periods based on objective electronic records of completed device sessions. Subjects were instructed to complete a device session on all days with RLS symptoms. The global criterion for success percentage was \>=70%. The adherence ratio is the average days per week subjects completed device sessions divided by the average number of days that subjects experienced RLS symptoms.

Group	Value	95% CI
Noninvasive Peripheral Nerve Stimulation (NPNS)	85	± 24

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 9 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Noninvasive Peripheral Nerve Stimulation (NPNS)

Serious: 0/20 (0%)

Deaths: 0/20

Other adverse events (3 terms — click to expand)

Reaction	System	Noninvasive Peripheral Ner…
Discomfort	General disorders	—
Skin irritation	Skin and subcutaneous tissue disorders	—
Restless Legs Syndrome	Musculoskeletal and connective tissue disorders	—

Data from ClinicalTrials.gov NCT04698343 adverse events section.

Sponsor's own description

Prospective open-label single-arm feasibility study assessing the tolerability of opioid medication reduction in conjunction with noninvasive peripheral nerve stimulation (NPNS) for patients taking prescription opioids to treat moderate-severe primary RLS.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Adjunctive tonic motor activation enables opioid reduction for refractory restless legs syndrome: a prospective, open-label, single-arm clinical trial.
   Buchfuhrer MJ, Roy A, Rodriguez S, Charlesworth JD. · · 2023 · cited 7× · PMID 37990163 · DOI 10.1186/s12883-023-03462-6