Novel Calcium Channel Modulators in RLS and Variants: Efficacy & Safety

Observation of Efficacy and Safety of Novel Calcium Channel Modulators in the Treatment of Restless Legs Syndrome and Its Variant Subtypes

The goal of this [study type: clinical trial] is to [primary purpose: evaluate the efficacy and safety of a novel calcium channel modulator in treating Restless Legs Syndrome (RLS) and its variant subtypes] in [describe participant population/primary condition: adult patients aged 18-75 years with confirmed RLS or its variant subtypes, who meet the study's eligibility criteria]. The main question[s] it aims to answer [is/are]:

• Does the novel calcium channel modulator improve RLS-related symptoms (assessed by the International Restless Legs Syndrome Study Group Rating Scale, IRLS) after the treatment period?
• What is the safety profile (incidence of adverse events) of this calcium channel modulator in RLS patients?

Participants will [describe the main tasks participants will be asked to do, interventions they'll be given]:

• Receive oral administration of the novel calcium channel modulator (40mg twice daily) for 12 consecutive weeks
• Complete scheduled follow-up visits for symptom assessments, safety monitoring, and questionnaire completion

Study Overview

• Status: Recruiting
• Conditions: Restless Leg Syndrome (RLS); Variant Restless Legs Syndrome
• Intervention / Treatment: Drug: Crisugabalin

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wenlu Zhao; Phone Number: 13017688128; Email: 912977992@qq.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100050
      • Recruiting
      • Capital Medical University Affiliated Beijing Friendship Hospital
      • Contact: Wenlu Zhao; Phone Number: 13017688128; Email: 912977992@qq.com
      • Contact: Houzhen Tuo; Phone Number: 13683628005; Email: tuohouzhen@ccmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Aged 18-75 years, regardless of gender.
• 2. Meets the diagnostic criteria for typical Restless Legs Syndrome (RLS) (IRLSSG criteria) or variant RLS confirmed by a neurologist.
• 3. Moderate to severe RLS (IRLS score ≥11).
• 4. Able to understand and comply with the study protocol, and provides written informed consent.

Exclusion Criteria:

• 1. Secondary RLS (e.g., iron deficiency anemia with serum ferritin <30μg/L, renal dysfunction with eGFR <30ml/min, pregnancy/lactation, drug-induced RLS with unadjustable medications).
• 2. Severe central nervous system diseases (e.g., status epilepticus, severe dementia, stroke within 3 months).
• 3. Severe cardiovascular diseases (e.g., congestive heart failure, uncontrolled hypertension with SBP≥180mmHg or DBP≥110mmHg).
• 4. Severe liver or kidney dysfunction (ALT/AST >3×ULN, eGFR <30mL/min/1.73m²).
• 5. Active mental illnesses (e.g., schizophrenia, acute bipolar disorder).
• 6. Hypersensitivity to Keligabalin Benzenesulfonic Acid or its excipients.
• 7. Participation in other clinical trials within 1 month, inability to cooperate with follow-up, or history of substance abuse.
• 8. Pregnancy or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crisugabalin Treatment Arm	Drug: Crisugabalin; Participants will receive oral administration of Crisugabalin for 12 consecutive weeks. No other drugs affecting RLS symptoms will be allowed during the study. Clinical assessments and safety monitoring will be conducted at scheduled follow-up visits.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in International Restless Legs Syndrome Scale (IRLS) Score from Baseline to Week 12	The International Restless Legs Syndrome Scale (IRLS) is a 10-item scale used to assess the severity of restless legs syndrome symptoms, including urge to move, sleep disturbance, and daytime impairment. The scale ranges from 0 to 40 points, with lower scores indicating less severe symptoms and a score of 0 indicating no symptoms. This outcome measure assesses the absolute change in IRLS total score from baseline (pre-treatment) to Week 12 (end of treatment).	Baseline (pre-treatment) and Week 12 (end of treatment)
Change in International Restless Legs Syndrome Scale (IRLS) Score from Baseline to Week 12	The International Restless Legs Syndrome Scale (IRLS) is a 10-item scale used to assess the severity of restless legs syndrome symptoms, including urge to move, sleep disturbance, and daytime impairment. The scale ranges from 0 to 40 points, with lower scores indicating less severe symptoms. This primary efficacy endpoint is defined as the percentage of participants achieving a ≥50% reduction in IRLS total score from baseline to Week 12, which is considered a clinically meaningful treatment response.	Baseline (pre-treatment) and Week 12 (end of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Restless Legs Syndrome Quality of Life (QoL-RLS) Score from Baseline to Week 12	This outcome evaluates the effect of treatment on participants' quality of life, focusing on physical, emotional, and social functioning related to RLS symptoms. The Restless Legs Syndrome Quality of Life (QoL-RLS) scale is a disease-specific instrument designed to measure the impact of RLS on daily life. The scale ranges from 0 to 100 points, with higher scores indicating better quality of life related to RLS symptoms. This outcome measure assesses the change in QoL-RLS total score from baseline (pre-treatment) to Week 12 (end of treatment).	Baseline (pre-treatment) and Week 12 (end of treatment)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Pittsburgh Sleep Quality Index (PSQI) Scores from Baseline to Week 12	This outcome evaluates the effect of the novel calcium channel modulator on participants' sleep quality. The Pittsburgh Sleep Quality Index (PSQI) is a 19-item self-rated questionnaire that assesses sleep duration, sleep latency, sleep disturbances, and daytime dysfunction. The scale ranges from 0 to 21 points, with lower scores indicating better sleep quality. This outcome measure assesses the change in PSQI total score from baseline (pre-treatment) to Week 12 (end of treatment).	Baseline (pre-treatment) and Week 12 (end of treatment）
Changes in Hamilton Anxiety Scale (HAMA) Scores from Baseline to Week 12	This outcome evaluates the effect of the novel calcium channel modulator on participants' anxiety symptoms. The Hamilton Anxiety Scale (HAMA) is a 14-item clinician-rated scale that assesses the severity of anxiety symptoms and emotional well-being. The scale ranges from 0 to 56 points, with lower scores indicating less severe anxiety symptoms. This outcome measure assesses the change in HAMA total score from baseline (pre-treatment) to Week 12 (end of treatment).	Baseline (pre-treatment) and Week 12 (end of treatment）
Changes in Hamilton Depression Scale (HAMD) Scores from Baseline to Week 12	This outcome evaluates the effect of the novel calcium channel modulator on participants' depressive symptoms. The Hamilton Depression Scale (HAMD) is a clinician-rated scale used to assess the severity of depressive symptoms and emotional well-being. The scale ranges from 0 to 52 points, with lower scores indicating less severe depressive symptoms. This outcome measure assesses the change in HAMD total score from baseline (pre-treatment) to Week 12 (end of treatment).	Baseline (pre-treatment) and Week 12 (end of treatment）

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital

Publications and helpful links

General Publications

• Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, Zucconi M, Ferri R, Trenkwalder C, Lee HB; International Restless Legs Syndrome Study Group. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria--history, rationale, description, and significance. Sleep Med. 2014 Aug;15(8):860-73. doi: 10.1016/j.sleep.2014.03.025. Epub 2014 May 17.
• Trenkwalder C, Allen R, Hogl B, Clemens S, Patton S, Schormair B, Winkelmann J. Comorbidities, treatment, and pathophysiology in restless legs syndrome. Lancet Neurol. 2018 Nov;17(11):994-1005. doi: 10.1016/S1474-4422(18)30311-9. Epub 2018 Sep 21.
• Suzuki K, Suzuki S, Miyamoto M, Miyamoto T, Matsubara T, Nozawa N, Arikawa T, Nakajima I, Hirata K. Involvement of legs and other body parts in patients with restless legs syndrome and its variants. J Neurol Sci. 2019 Dec 15;407:116519. doi: 10.1016/j.jns.2019.116519. Epub 2019 Oct 20.
• Ishizuka K, Ohira Y. Restless Chest Syndrome: A Rare Variant of Restless Legs Syndrome. Eur J Case Rep Intern Med. 2022 Jul 6;9(7):003398. doi: 10.12890/2022_003398. eCollection 2022.
• Jung Y, Hassan A, St Louis EK, Robertson CE. Restless mouth syndrome. Neurol Clin Pract. 2017 Jun;7(3):e29-e30. doi: 10.1212/CPJ.0000000000000280. No abstract available.

Study record dates

Study Major Dates

• Study Start (Estimated): March 10, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: February 2, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Parasomnias; Restless Legs Syndrome
• Other Study ID Numbers: BFH20251127008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: This study is in the exploratory stage, and the plan for sharing individual participant data (IPD) has not yet been finalized. The decision will be made based on the study results, publication requirements, and ethical considerations at the completion of the study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No