# Restless legs syndrome

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Tags: [Drugs and biologics](../BROWSE.md#drugs) · [Devices and procedures](../BROWSE.md#devices-procedures)

## Current state

Newly recovered IV-iron and extended-duration TOMAC programs target refractory RLS and awakenings. An uncontrolled venous-ablation association does not establish a general RLS cure or causal benefit.

**Coverage:** Selected inherited baselines and new programs were reviewed October 6, 2026. Complete literature, registry and informal-source coverage remains pending; older source dates are preserved.

Status: active. Topic ID: `sleep_restless_legs`.

## Questions to follow

- Discover meaningful human trials of medicines, iron-related treatments and nerve-stimulation or other devices, beyond the saved Nidra program.
- Retain primary versus secondary disease, iron status, baseline severity and refractory-treatment criteria; distinguish symptom change from improved sleep and daily function.
- Follow augmentation, withdrawal/rebound, adherence, adverse effects, longer-term durability and U.S. access; do not infer effectiveness from an uncontrolled extension.

## Programs and next milestones

### Focused update — 2026-10-16

No additional finding was selected from these checked sources. Coverage remains incomplete; this is not a full-topic “no news” conclusion.

**Remaining gaps:** Read current canonical scope, shared summaries, state and assigned topic notes. Bounded registry discovery covered July 18–October 16, 2026; prior October 13 findings were deduplicated. Full-topic successful-check dates remain unchanged.; Retrieved all 14 records across 1 pages of the bounded ClinicalTrials.gov query, plus 7 named records. Selected relevant new/changed protocols were appraised; downloading all records does not establish exhaustive safety/results review.; Europe PMC original-literature discovery failed with HTTP 503 for this topic. Targeted primary-source web searches supplied a partial fallback. Worldwide literature, regulators, international registries and complete original conference/podcast recordings remain incomplete.; The new condition baseline remains incomplete. Preceding 90-day registry discovery and selected inherited pivotal context were checked; the full older clinical, label and behavioral/device evidence corpus has not been completed.; Saved iron, TOMAC, CBD and implanted/noninvasive stimulation records refreshed. No new RLS program result selected. October-issue TOMAC correction/full methods still need appraisal; a recent issue or mirror refresh was not treated as a new trial. Complete older drug/iron safety, augmentation, special-population and original conference baseline remains incomplete.

**Informal-source coverage:** Targeted RLS Reddit searches and the prior algorithm thread were deduplicated. Personal drug, device and food-trigger experiences do not establish a new clinical program or cure. No distinct new attributable rumor selected; full SOS/SLEEP recordings and broader informal signals remain gaps.

[Full coverage record](../updates/2026-10-16_scheduled_research_update.md).


### Focused update — 2026-10-13

<span class="note-anchor" id="note-2025-09-17-scs-neurophysiology-baseline"></span>

#### A separate spinal-cord-stimulation study investigates RLS physiology

**Older baseline recovered October 13 — NCT07179406.** University of Alabama at Birmingham plans **50 people** in four nonrandomized unmasked groups: RLS/healthy controls, RLS with an existing spinal cord stimulator, RLS scheduled for implantation, and chronic pain with a stimulator but no RLS.

Primary outcomes are changes in **H-reflex, SSEP, vibratory evoked potentials and TMS responses** within three weeks of consent. This studies neural physiology; it is not a randomized sham comparison of RLS symptoms, sleep, daily function or long-term safety. No results. It is also distinct from **NO RLS, NCT07780032**, the previously saved 15-person implanted-device safety feasibility program.

The primary registry last updated **June 26, 2026** says recruiting, actual start **August 4, 2025**; estimated primary completion **January 31, 2028**, final **December 31, 2028**. A mirror's October 13 synchronization is not a new start/recruitment update or new RLS marketing authorization.

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07179406).

**Remaining gaps:** Read current canonical scope, shared summaries/state and assigned topic notes. September 5–October 13 overlap preserves the September 12 full-review dates; October 6/9 entries were deduplicated. All pages of each bounded ClinicalTrials.gov query were downloaded, and named records plus selected relevant new/changed protocols were appraised. This is focused partial review, not a worldwide full literature/regulator/safety census; successful full-topic dates must remain unchanged.; Bounded query retrieved 7 records across 1 pages; incidental studies excluded. Named topic records refreshed: 6. Full older evidence, international registries, comprehensive harms and all original conference/podcast recordings remain gaps.; New condition-specific baseline remains incomplete. Selected inherited older pivotal sources and newly recovered formal programs were reviewed, without declaring the preceding 90-day/older trial corpus complete.

**Informal-source coverage:** Reviewed the original October 7 RLS-algorithm discussion and October 9 patient thread. Drug, stevia and device experiences are not formal new trial results. A TOMAC meta-analysis/corrigendum appears in an October issue, but the original publication date and full correction remain unappraised; the issue date is not treated as new research. No distinct new development rumor was selected. Full SOS/SLEEP presentations and audio remain incomplete.

[Full coverage record](../updates/2026-10-13_scheduled_research_update.md).


### Focused update — 2026-10-09

<span class="note-anchor" id="note-2026-05-26-rls-algorithm2026-baseline"></span>

#### Updated RLS treatment algorithm supplies a current clinical context

**Older clinical context recovered through an October 7 Reddit lead.** Silber and colleagues' *An Updated Algorithm for the Management of Restless Legs Syndrome* was first published **May 26, 2026**, in the **September 2026** issue of Mayo Clinic Proceedings (101:1561–1588; DOI 10.1016/j.mayocp.2026.05.010). It is an expert/literature-based algorithm, not a new randomized trial.

The primary abstract emphasizes iron evaluation and oral/IV options, **gabapentinoids as first-line pharmacologic treatment for chronic persistent RLS**, dopamine-agonist risks and augmentation, selected low-dose opioid management, and newer approaches including **peroneal nerve stimulation and buprenorphine**. Special populations are addressed separately.

Only the original indexed abstract and bibliographic dates were reviewed; full dosing/threshold recommendations are not reproduced. The October 7 discussion does not make the May publication new medical news. This provides baseline framing alongside the 2025 AASM guidance; new program efficacy, safety and U.S. access must still be judged separately.

**Sources:** [Primary source 1](https://pubmed.ncbi.nlm.nih.gov/42203073/); [Primary source 2](https://doi.org/10.1016/j.mayocp.2026.05.010); [Primary source 3](https://www.reddit.com/r/RestlessLegs/comments/1x0bai6/an_updated_algorithm_for_the_management_of/).

<span class="note-anchor" id="note-2026-10-08-brc002-baseline"></span>

#### A placebo-controlled CBD-extract trial is planned for idiopathic RLS

**Baseline recovery — BRC-002, NCT07224932.** University of Colorado plans **60 patients with idiopathic RLS** in a masked randomized placebo-controlled phase 2 trial of an oral high-CBD botanical extract containing **less than 0.3% THC**.

Primary is safety/tolerability based on adverse events, examinations, vital signs and laboratory monitoring; secondary day-20 outcomes include **IRLS symptoms**, sleep quality, daytime sleepiness, fatigue, cognition and mood. A device-derived sleep-quality score is not proof of restored REM/deep sleep architecture. No results are posted.

The October 8 registry still says **not yet recruiting**, with **November 1, 2026 estimated start**, **March 14, 2028 estimated primary completion**, and **June 1, 2028 final completion**. First registration was **November 5, 2025**; this is baseline program recovery, not a brand-new October trial announcement. General CBD commercial availability does not establish FDA approval for RLS.

**Sources:** [Primary source 1](https://clinicaltrials.gov/study/NCT07224932).

<span class="note-anchor" id="note-2026-08-21-norlsscs-baseline"></span>

#### An implanted spinal-cord stimulation feasibility study is planned for refractory RLS

**Baseline context — NO RLS, NCT07780032.** This University of Alabama at Birmingham/NINDS-supported first-in-indication feasibility study plans **15 people with severe treatment-refractory primary RLS**, implanted with the Saluda Evoke spinal-cord stimulation system and followed for 24 months.

Primary is **device-, stimulation- and procedure-related adverse events**. Symptoms, function and other patient outcomes are secondary. This uncontrolled single-centre design cannot establish superiority over sham, drugs, iron or noninvasive peroneal stimulation; an implanted spinal-cord device is a materially different intervention from Nidra.

Registered **August 21, 2026**, the October 9 record remains **not yet recruiting**. Start is estimated **October 2027**, primary completion **October 2033**, final **October 2034**—all month precision, not promises. No results or RLS-specific U.S. marketing authorization are established by this registry.

**Sources:** [Primary source 1](https://clinicaltrials.gov/study/NCT07780032).

**Remaining gaps:** New condition baseline remains incomplete. Reviewed inherited hub, preceding 90-day development leads and selected older pivotal/contextual sources; October 6 findings deduplicated.; 93 named NCT records across the ten topics and ten discovery queries downloaded successfully through the ClinicalTrials.gov public API. Download is not a claim that all fields/safety/results were exhaustively appraised.; Focused review only. Do not advance full successful-check timestamps or label incomplete remaining searches as no news.; All seven matches in bounded RLS discovery downloaded; selected relevant records screened. Selected older trial/guideline anchors added; full drug/iron labeling, safety, pediatric/pregnancy and older trial corpus remain incomplete. Venous-ablation full methods/harms gap persists; no cure conclusion.

**Informal-source coverage:** Original October 7 RLS algorithm thread led to a verified May 26 original publication. Individual October device/medication experiences are not trial efficacy. Full SLEEP/SOS recordings and podcast interviews remain incomplete.

[Full coverage record](../updates/2026-10-09_scheduled_research_update.md).


### Focused update — 2026-10-06

<span class="note-anchor" id="note-2026-09-16-rlsiron"></span>

#### New refractory-RLS trial compares immediate with delayed IV iron

**Source/event date: September 16, 2026. Evidence: new registration recovered during sleep baseline.** A French open-label randomized phase 2 study plans 66 adults with drug-resistant severe RLS on stable background therapy, comparing immediate IV ferric carboxymaltose with treatment delayed 12 weeks. Primary: IRLSSG severity score through week12; sleep, daytime symptoms, quality of life, iron and augmentation measures continue through week24. NOT_YET_RECRUITING; October2026 estimated start, April2029 primary and October2030 final completion. No effect/safety estimates. This extends the saved device-only research baseline; it does not establish a new IV-iron benefit, U.S. RLS indication or confirmed start.

[Source 1](https://clinicaltrials.gov/api/v2/studies/NCT07822607) · [Source 2](https://clinicaltrials.gov/study/NCT07822607)

<span class="note-anchor" id="note-2026-06-30-xdtomac"></span>

#### Extended-duration TOMAC study targets RLS-related awakenings

**Historical baseline addition reviewed October 6, 2026.** NCT07675109 recruits 20 planned adults to optimize extended-duration TOMAC. It uses a participant-masked crossover/pseudo-randomized sequence of three device settings in the final six weeks, with total assessments over 12 weeks. Primary: RLS-related awakenings/night; symptoms, sleep and quality of life are secondary. Actual start June8,2026, estimated primary completion December2026 and final June2027; no results. This is optimization of investigational extended-duration therapy, not proof that an existing prescription device’s indication includes the new setting. Small selected cohorts and comparisons with baseline cannot establish broad long-term benefit or safety.

[Source 1](https://clinicaltrials.gov/api/v2/studies/NCT07675109) · [Source 2](https://clinicaltrials.gov/study/NCT07675109)

<span class="note-anchor" id="note-2026-09-16-rfa"></span>

#### Venous-ablation RLS report is an uncontrolled association

**Source/event date: September 16, 2026; abstract recovered October 6. Evidence: uncontrolled pre–post observational study.** In 160 consecutive patients with symptomatic chronic venous insufficiency treated in 2022–2023, median RLS severity declined 21→7 and sleep-quality score 6→4 within three months after radiofrequency ablation (both P<.001). Excessive daytime sleepiness prevalence did not significantly change (7.5%→5.6%, P=.317).

There was no untreated/sham comparator; regression to the mean, expectation and changes in venous discomfort can explain part of the association. Full methods, formal RLS confirmation, concomitant medication changes and procedural harms were not appraised; confidence intervals and safety counts were absent from the abstract. This does not establish venous ablation as a general RLS treatment or create a U.S. RLS indication. The previously saved full-methods gap remains despite clearer abstract-level context.

[Source 1](https://journals.sagepub.com/doi/10.1177/02683555261490768)

**Coverage:** 2026-10-06: RLS SeptemberOctober2026 trial iron perampanel Nidra; 2026-10-06: RLS interventional registry30latest; NCT07822607/NCT07675109; 2026-10-06: September16 venousRFA original abstract; AASM2025guideline; 2026-10-06: RedditRestlessLegs Oct3Nidra and trial publication anecdotes

**Remaining gaps:** Pending condition baseline partially expanded beyond Nidra with IViron randomized timing trial, XD-TOMAC and controlled/observational discovery. Latest30RLS interventional records screened; important older drug/iron trials, guidance and safety still need full reconciliation.; September16 venous-ablation full methods/harms remain inaccessible. AASM2025guideline indexed primary text reviewed, directPMC returned recaptcha; full guideline/label baseline not complete. ConferenceSOS2026fulltalks and original podcasts not appraised.

**Informal-source coverage:** Read Oct3 original Only-The-ShadowKnows thread: mixed personal drug/device experiences and anonymous comments predicting Stanford-study publication; no attributable source/date for a new formal readout, so no efficacy/launch rumor promoted. OriginalSOS2026talks/audio not reviewed.

[Full coverage record](../updates/2026-10-06_scheduled_research_update.md).


### Nidra / NTX100 nerve stimulation

**Development / U.S. status:** FDA De Novo DEN220059 was granted April 17, 2023, for a prescription device for medication-refractory moderate-to-severe primary RLS. This is historical baseline context, not a new approval.

**Evidence / limitations:** In the 133-person RESTFUL trial (NCT04874155), four blinded weeks produced CGI-I response rates of 45% versus 16% with sham and an IRLS difference of −3.4 points. Discomfort and skin irritation were generally mild; no severe or serious device-related adverse events were reported. The NCT05196828 extension was open-label, so it cannot establish long-term blinded comparative effectiveness.

**Next milestone:** Long-term controlled sleep/function, adherence, harms and access evidence; no firm next date verified. [FDA authorization](https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?id=DEN220059) · [FDA review](https://www.accessdata.fda.gov/cdrh_docs/reviews/DEN220059.pdf) · [RESTFUL publication](https://pubmed.ncbi.nlm.nih.gov/37458698/) · [Extension](https://pubmed.ncbi.nlm.nih.gov/37439365/) · [Original notes](12_sleep.md#sleep-restless-legs-baseline).

### Broader drug and device research

The prior October 2 check did not comprehensively appraise RLS conference full presentations or the September 16 observational venous-ablation paper. These remain explicit coverage gaps, not evidence of benefit or no news. The condition-specific drug/iron baseline requires a focused refresh.

## Dated history

### October 3, 2026 — Topic organization

Created this condition-specific entry from existing sleep coverage. Earlier sources, program dates, historical findings and successful research-check timestamps were preserved. See the [organization record](../updates/2026-10-03_sleep_category_organization.md) and [original history](12_sleep.md#dated-history). This is a navigation and baseline projection, not a new medical-news event.