ALS Clinical Trials Recruiting Now: Ranolazine for Muscle Cramps in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive neurodegenerative disorder affecting motor neurons in the brain and spinal cord. As motor neurons degenerate, patients experience muscle weakness, atrophy, fasciculations, and painful muscle cramps—reported in 92–95% of people with ALS, with two-thirds identifying cramps as their sole source of pain. Despite this high burden, no therapies are FDA-approved specifically for ALS-related cramps.

A new Phase 2, placebo-controlled trial is now recruiting to test whether ranolazine—a medication already FDA-approved for chronic angina—can safely reduce cramp frequency and severity in ALS.

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Actively Recruiting Trial: Ranolazine in ALS (NCT06527222)

NCT ID: NCT06527222
Sponsor: University of Kansas Medical Center
Phase: 2
Status: RECRUITING
Estimated Enrollment: 70 participants
Study Design: Randomized, double-blind, placebo-controlled, parallel-group
Intervention: Ranolazine extended-release 1000 mg twice daily vs. matching placebo
Duration: 12-week treatment period with follow-up
Primary Outcome: Safety and tolerability; change in cramp frequency and severity

Key Locations (United States):

• San Francisco, California — University of California, San Francisco (UCSF)
• Jacksonville, Florida — University of Florida
• Fairway, Kansas — University of Kansas Medical Center
• Wichita, Kansas — University of Kansas Medical Center, Wichita
• Columbia, Missouri — University of Missouri
• Columbus, Ohio — The Ohio State University

Key Eligibility Criteria (summary):

• Adults 18+ with confirmed ALS (El Escorial criteria: clinically probable, probable with laboratory support, or definite)
• Experiencing muscle cramps at least 4 times per week during the 2-week run-in period
• Able to swallow oral medication
• Forced vital capacity (FVC) ≥ 50% predicted
• Stable riluzole and/or edaravone regimen for ≥ 30 days (if taking)

Exclusions include: Uncontrolled cardiac disease, QTc > 450 ms, severe hepatic impairment, creatinine clearance < 30 mL/min, pregnancy, or participation in another interventional trial.

Full eligibility is determined by the study team. Pre-qualification on Corterve is a first step only.

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Why Ranolazine for ALS Cramps?

Ranolazine is a late sodium current inhibitor approved for chronic angina. Preclinical and clinical data suggest it reduces neuronal hyperexcitability—a key mechanism in ALS pathogenesis and cramp generation.

Evidence from a pilot open-label study (Chandrashekhar et al., Muscle Nerve 2022, PMID 35466411):

• 14 ALS patients received ranolazine 500 mg or 1000 mg twice daily for 4 weeks
• No serious adverse events; most common side effect was gastrointestinal (40%)
• Cramp frequency decreased 54.8% (95% CI 39–70.8%)
• Cramp severity decreased 46.3% (95% CI 29.5–63.3%)
• Effect appeared dose-dependent; reduced nocturnal awakening from cramps

This pilot supports advancing to a placebo-controlled Phase 2 trial—the study now recruiting at six U.S. academic centers.

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Standard Management vs. Investigational Approaches for ALS Cramps

Approach	Examples	Typical Use Case	Limitations
Symptomatic / Off-label	Mexiletine, gabapentin, baclofen, levetiracetam, quinine (limited)	Empiric cramp suppression	Limited ALS-specific evidence; side effects (GI, cardiac, sedation); quinine no longer recommended
Multidisciplinary ALS Care	Physical therapy, stretching, hydration, electrolyte repletion	First-line supportive care	Does not address neuronal hyperexcitability directly
Investigational (Ranolazine in NCT06527222)	Ranolazine ER 1000 mg BID vs. placebo	ALS with frequent cramps; FVC ≥ 50%	Investigational—not approved for ALS or cramps; cardiac monitoring required
Other ALS Trials	Tofersen (SOD1-ALS), masitinib, CNM-Au8, AMX0035, gene therapies	Varies by genotype/disease stage	Target disease progression, not specifically cramps

Note: This table is for informational purposes only. Treatment decisions should be made with your neurologist and ALS care team.

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How Corterve Helps Patients Find ALS Trials

Corterve's matching platform connects patients to actively recruiting studies using:

1. Condition-specific search — Filter for "amyotrophic lateral sclerosis," "ALS," "motor neuron disease," or "Lou Gehrig's disease"
2. Location + travel radius — See trials at UCSF, University of Florida, KU Medical Center, University of Missouri, Ohio State, and other sites near your ZIP code
3. Structured pre-screening — 4–6 questions covering diagnosis confirmation, cramp frequency, respiratory function, medication stability, and travel willingness
4. Direct site referral — If you pre-qualify, we connect you to the study coordinator for formal screening

Search actively recruiting ALS trials: Corterve ALS Trials

Get personalized alerts: Register with your ZIP code to be notified when new ALS studies open near you.

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Questions to Ask Your Neurologist or ALS Study Team

• Do my cramp frequency and severity meet the trial's entry criteria (≥ 4/week)?
• Is my current respiratory function (FVC) compatible with the study's ≥ 50% threshold?
• How does ranolazine's cardiac monitoring (ECG, QTc) fit with my cardiac history?
• Could ranolazine interact with my current medications (riluzole, edaravone, others)?
• What is the time commitment—visits, ECGs, labs, diaries—and is travel support available?
• If I receive placebo, what are my options after the 12-week period (open-label extension?)?
• Are there other recruiting ALS trials (e.g., targeting SOD1, TDP-43, neuroinflammation) that might fit my profile?

Important: Pre-qualification on Corterve identifies potential matches only. The research site's team makes the final eligibility determination after full medical review, including ECG, labs, and neurological exam. ALS care decisions should always involve your multidisciplinary ALS clinic team.

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Take the Next Step

Search actively recruiting ALS trials now: Corterve ALS Trials

Register for new-trial alerts: Get notified when ALS studies open at centers near you.

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Disclaimer: Corterve is a clinical trial matching platform, not a medical provider. We do not give medical advice, diagnose conditions, or guarantee trial eligibility or outcomes. All eligibility determinations and medical decisions are made by the study's research team and your healthcare providers. This post uses publicly available trial metadata (ClinicalTrials.gov NCT06527222) and peer-reviewed literature (Chandrashekhar et al., Muscle Nerve 2022, PMID 35466411) for informational purposes only. Consult a qualified healthcare professional before considering any clinical trial or changing your treatment plan.

Last verified: 2026-07-21. Recruitment status and site availability can change; confirm current status on ClinicalTrials.gov or with the study coordinator.