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Home › Conditions › Restless Legs Syndrome

Restless Legs Syndrome

Part of Sleep Disorders, Intrinsic

6 published articles · Updated continuously

Clinical Trial Landscape

Clinical Trials for Restless Legs Syndrome

45 trials tracked for Restless Legs Syndrome: 17 in phase 3 or 4 and 1 with published results. The most-cited published study has 5 citations.

45Trials tracked
17Phase 3 & 4
0Recruiting
1With published results
Phase distribution
Phase 4 6 Phase 3 11 Phase 2 13 Other / NA 15
  1. Phase 4 Efficacy of Suvorexant in Patients With Effectively Treated Restless Legs Syndrome and Persistent Chronic Insomnia Completed · 5 cited
  2. Phase 4 Switching From Oral Dopamine Agonists to Rotigotine Completed
  3. Phase 4 Gabapentin Enacarbil (GSK1838262) Adult Restless Leg Syndrome (RLS) Post Marketing Commitment Study Completed
  4. Phase 4 Effects of Neupro on Cardiovascular Observations in Patients With Restless Legs Syndrome Completed
  5. Phase 4 Long-term Study Of Ropinirole In Restless Legs Syndrome Completed
  6. Phase 4 Long-term Efficacy, Safety and Tolerability of Pramipexole in Patients With Idiopathic Moderate to Severe Restless Legs Syndrome (RLS) Completed
Show 39 more trials
  1. Phase 3 Converting From Ropinirole Immediate Release (IR) To Ropinirole Controlled-Release for RLS (Restless Legs Syndrome) Completed
  2. Phase 3 Long-Term Study of Gabapentin Enacarbil (GEn, XP13512) vs. Placebo in Patients With Restless Legs Syndrome. Completed
  3. Phase 3 Rotigotine Effect on All-day Functioning and Quality of Life in Subjects With Moderate to Severe Restless Legs Syndrome (RLS) Completed
  4. Phase 3 A Sleep Laboratory Study to Investigate the Safety and Efficacy of the Rotigotine Skin Patch in Subjects With Restless Legs Syndrome and End-Stage Renal Disease Requiring Hemodialysis Completed
  5. Phase 3 XP13512 (Gabapentin Enacarbil) Extension Study in Patients With Restless Legs Syndrome. Completed
  6. Phase 3 Polysomnography Study of GSK1838262 Extended Release Tablets Versus Placebo in RLS and Associated Sleep Disturbance Completed
  7. Phase 3 XP13512 vs. Placebo in Patients With Restless Legs Syndrome. Completed
  8. Phase 3 Polysomnography Study Of Pregabalin And Pramipexole Versus Placebo In Patients With Restless Legs Syndrome And Associated Sleep Disturbance Completed
  9. Phase 3 The Effects Of Ropinirole On Mood Or Mild Depression In Patients With Moderate To Severe Restless Legs Syndrome Completed
  10. Phase 3 Bupropion and Restless Legs Syndrome Completed
  11. Phase 3 Pramipexole in Out-patients With Idiopathic Restless Legs Syndrome (IRLS) Completed
  12. Phase 2 Long-term Open-label Trial in Idiopathic Restless Legs Syndrome (RLS) Completed
  13. Phase 2 Simulated Driving Study in Restless Legs Syndrome Completed
  14. Phase 2 Treatment of Restless Leg Syndrome (RLS) Augmentation With Ecopipam, a D1 Specific Antagonist Completed
  15. Phase 2 Iron Sucrose In The Treatment of Restless Legs Syndrome: Safety of Three Dose Regimens as Evaluated by Clinical Assessments Completed
  16. Phase 2 Clinical Evaluation of Ropinirole CR-RLS ( SK&F101468)Tablets in Restless Legs Syndrome Completed
  17. Phase 2 Study to Investigate Pharmacokinetics (PK) of Pramipexole in Pediatric Patients Who Are Individually Optimized to Stable Pramipexole Doses for the Treatment of Idiopathic Restless Legs Syndrome (RLS) Completed
  18. Phase 2 Dose-Response and Pharmacokinetics of Gabapentin Enacarbil (GEn [XP13512 / GSK1838262]) in Restless Legs Syndrome Completed
  19. Phase 2 Efficacy, Safety and Tolerability of Rotigotine Nasal Spray for the Acute Treatment of RLS Symptoms Completed
  20. Phase 2 Pilot Study: Randomized, Placebo-controlled Comparator Trial of IV vs Oral Iron Treatment of RLS With IDA. (IVOR-IDA) Completed
  21. Phase 2 Long-Term Follow-Up Study for Safety, Efficacy and Tolerability of Rotigotine in Adolescents With Restless Legs Syndrome Completed
  22. Phase 2 Botulinum Toxin to Treat Restless Legs Syndrome Completed
  23. Phase 2 Lyrica Dose Response Study With Restless Legs Syndrome (RLS) Patients Completed
  24. Phase 2 Dose Escalating Study of Rotigotine in Pediatric Subjects With Restless Legs Syndrome Completed
  25. N/A Non-interventional Observational Study on the Influence of Pramipexole on Sensory Symptoms of Restless Legs Syndrome (RLS) Completed
  26. N/A Advancing Understanding of Transportation Options Completed
  27. N/A A Study on the Use of the MMF07 Foot Massager and Heat Therapy Treatments for Restless Leg Syndrome Completed
  28. N/A Gabapentin and Risk of Pancreatic Cancer and Renal Cancer (GPRD) Completed
  29. N/A REQUIP RLS Post Marketing Surveillance Completed
  30. N/A Spinal Cord Stimulation for Restless Legs Syndrome Completed
  31. N/A Noninvasive Peripheral Nerve Stimulation for Restless Legs Syndrome During Opioid Medication Reduction Completed
  32. N/A Treatment of RLS/WED Symptoms Through Sensory Counter-stimulation Completed
  33. N/A Survey on Long-Term Use of BI-Sifrol® Tablets in Patients With Restless Legs Syndrome Completed
  34. N/A Safety and Effect of Mirapex(Pramipexole) Tablet Among Korean RLS Completed
  35. N/A Noninvasive Peripheral Nerve Stimulation for Medication-Refractory Primary RLS (The RESTFUL Study) Completed
  36. N/A Sifrol (Pramipexole) Onset of Action and Impact: a 12-weeks Observational Study in Patients With Primary Restless Legs Syndrome Completed
  37. N/A The Effect of Horizant (Gabapentin Enacarbil) on Augmentation Completed
  38. N/A Extension Study Evaluating NTX100 Neuromodulation System for Medication-Refractory Primary RLS Completed
  39. N/A Effect on RLS Symptom Severity After Switching to Neupro® in Patients Who Previously Experienced Augmentation Completed

Showing the 45 most-cited and recently-updated of 45 trials. Browse the full registry →

Trial data sourced from ClinicalTrials.gov. Counts describe the research landscape and are not a treatment recommendation. Informational only — not medical advice.

What the trials found Updated — new results For clinicians

Restless Legs Syndrome: what the trials found

Several pharmacological interventions have demonstrated efficacy in reducing International Restless Legs Syndrome (IRLS) scores. Pramipexole showed significant reductions in IRLS total scores at 6 weeks 17 and 26 weeks 7, with high responder rates on the Clinical Global Impression - Improvement (CGI-I) scale [7, 17]. Rotigotine was associated with a reduction in the Periodic Limb Movement Index (PLMI) 9 and significant reductions in systolic blood pressure elevations associated with periodic limb movements 5.

Specific formulations and compounds have shown measurable impact on symptoms and sleep quality. GSK1838262 (including extended-release versions) demonstrated statistically significant improvements in IRLS scores [4, 16], a dose-response relationship for IRLS reduction 4, and reductions in Wake Time During Sleep (WTDS) and Periodic Limb Movements Associated with Arousal (PLMAI) 15. XP13512 (GEn) showed significant improvements in IRLS scores over time [13, 16] and a lower rate of relapse compared to placebo 14. Additionally, pregabalin was associated with significant improvements in Wake After Sleep Onset (WASO), Periodic Limb Movement Arousal Index (PLMAI), and Subjective Total Sleep Time (sTST) 11.

Secondary outcomes for RLS management include the impact on comorbid conditions. Ropinirole showed statistically significant reductions in MADRS and HAM-D scores over 12 weeks of treatment, particularly in patients with signs of moderate depression 18.

Recent results — preliminary, needs further review

  • Ecopipam was evaluated in a Phase 2 trial (N=10), but results are not yet corroborated.

For the clinician treating this condition

  • Pramipexole and Rotigotine are established options for reducing IRLS scores and managing associated periodic limb movements.
  • GSK1838262 and XP13512 provide evidence-based improvements in IRLS scales and related sleep metrics like WTDS and PLMAI.
  • Pregabalin shows significant efficacy in improving specific sleep parameters including WASO and sTST.

AI synthesis of 9 cited trials, updated Jun 25, 2026. Informational only — not medical advice; trial data sourced from ClinicalTrials.gov. How we use AI.

HCP Mode — summaries include clinical detail, trial data, and statistical outcomes.
Patient Mode — summaries use plain language, avoiding clinical jargon.
Meta-analysis identifies genetic loci and biomarkers for restless legs syndrome in over 1.3 million individuals
Genetics & Precision Medicine Meta-analysis
Meta-analysis identifies genetic loci and biomarkers for restless legs syndrome in over 1.3 million individuals Genetic study links over 100 conditions to restless legs syndrome
This meta-analysis synthesizes genome-wide and phenome-wide association analyses from UK Biobank and All of Us cohorts involving more than 1…
A massive genetic analysis connects restless legs syndrome to more than 100 other diseases, lifestyle factors, and biomarkers in over 1.3 mi…
medRxiv May 23, 2026
Meta-analysis finds pharmacologic therapies improve RLS in hemodialysis patients
Neurology Meta-analysis
Meta-analysis finds pharmacologic therapies improve RLS in hemodialysis patients Medications help restless legs in dialysis patients
This systematic review and meta-analysis synthesized evidence on pharmacologic therapies for restless legs syndrome in adults undergoing mai…
A review of studies shows certain medicines can ease restless legs and improve sleep for people on dialysis. Some options work better than o…
Frontiers May 20, 2026
Meta-analysis identifies ancestry-specific and shared genetic loci for restless legs syndrome in diverse populations
Genetics & Precision Medicine Meta-analysis
Meta-analysis identifies ancestry-specific and shared genetic loci for restless legs syndrome in diverse populations Genetic study finds new risk factors for restless legs syndrome in diverse populations
This meta-analysis examines genome-wide association data from biobank-based cohorts involving African, Latin American, and European ancestry…
A large genetic study reveals new risk factors for restless legs syndrome in African, Latin American, and European ancestry groups.
medRxiv Apr 30, 2026
Machine learning model identifies RLS in ESRD patients with AUC 0.791
Neurology Cohort
Machine learning model identifies RLS in ESRD patients with AUC 0.791 Machine learning model helps identify restless legs in dialysis patients
This cohort study of 396 end-stage renal disease patients undergoing dialysis developed a machine learning classification model to identify …
A new machine learning model shows promise for spotting restless legs syndrome in people with end-stage kidney disease undergoing dialysis.
Frontiers Apr 29, 2026
Review finds bed partners have more sleep apnea than pregnant co-sleepers in third trimester
OB/GYN & Women's Health
Review finds bed partners have more sleep apnea than pregnant co-sleepers in third trimester Pregnant women sleep better than their partners despite restlessness
This review of an observational study examined sleep physiology in 41 pregnant participants and 36 bed partners.
Healthy pregnant women sleep better than their bed partners, who face a much higher risk of severe sleep apnea during this time.
medRxiv Apr 26, 2026
Two-week active tsDCS improved RLS symptoms and neurophysiological measures versus sham in a small RCT
Anesthesiology & Pain Medicine RCT
Two-week active tsDCS improved RLS symptoms and neurophysiological measures versus sham in a small RCT Could a two-week treatment ease restless legs and improve sleep for patients?
This randomized controlled trial evaluated active transcutaneous spinal cord direct current stimulation (tsDCS) versus sham stimulation in 3…
A two-week electrical stimulation treatment significantly eased restless legs symptoms and improved sleep quality compared to a fake treatme…
Apr 6, 2026

Questions about Restless Legs Syndrome

Are there shared genetic factors for restless legs across different populations?

Research shows that restless legs syndrome (RLS) has both shared genetic factors across different populations and unique genetic markers specific to certain ancestries.

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Did a recent trial show active stimulation helps restless legs better than sham?

A 2024 trial found that active transcutaneous spinal cord stimulation reduced restless legs symptoms significantly more than a fake (sham) treatment over two weeks.

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Can transcutaneous spinal cord stimulation improve restless legs symptoms?

Yes, early research shows transcutaneous spinal cord stimulation (tsDCS) can significantly improve restless legs symptoms and sleep quality, but larger studies are needed.

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Does a machine learning model help diagnose restless legs in dialysis patients?

Yes, a machine learning model can help diagnose restless legs syndrome in dialysis patients, with one study reporting an AUC of 0.791.

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Can genetic ancestry affect my risk for restless legs syndrome?

Genetic ancestry does affect risk for restless legs syndrome, with specific risk genes found in African and Latin American populations that differ from those in European groups.

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See all 5 questions about Restless Legs Syndrome →