Table 1.

Inclusion and exclusion criteria

Inclusion criteria

1. Study participants are included if they meet the following inclusion criteria: 2. Diagnosed with ALS, PMA, or PLS based on the El Escorial ALS Diagnostic Criteria or based on more recently revised Gold Coast ALS diagnostic criteria [35, 36] 3. Experience at least 5 muscle cramp per week 4. Age 20–84 years old 5. Forced vital capacity is 45% of normal or greater in a seated position 6. Able to swallow liquid via the mouth or be given via a feeding tube 7. Caregiver available to assist with speaking or writing on behalf of the participant if they are not able to speak or write due to the disease 8. Understand the informed consent procedure and are able to give informed consent 9. Willing study participants are included if they meet the following inclusion criteria: 10. to commute to the study site for frequent visits, including a screening visit (study visits at the end of weeks 2, 5, 8, and 11) 11. Taking a stable dose of riluzole (Rilutek®), edaravone (Radicava®), AMX0035 (relyvrio ®), or all three both for at least a month before randomization and not expected to require dose titration or initiation of these medications during the study period 12. Willing to discontinue over-the-counter (OTC) products containing peony root, Glycyrrhiza, or both 13. Willing to discontinue mexiletine, quinine sulfate, or ranolazine during the study period 14. Willing to avoid food, beverages, and medications that may induce or inhibit metabolism enzyme or transporters 15. Willing to refrain from initiation or dose adjustment of baclofen, gabapentin, pregabalin, and/or memantine during the study period (stable dosing of these medications is allowed) 16. Willing to practice contraceptive measures for male and female patients

Exclusion criteria

1. Study participants will be excluded from the study based on the following exclusion criteria: 2. History of allergic reactions to peony root, Glycyrrhiza, or FD&C Yellow No. 5 (tartrazine) 3. Takes any medication known to increase the risk of pseudoaldosteronism or hypokalemia, including corticosteroids and diuretics (except potassium sparing diuretics, such as spironolactone or amiloride) 4. History of pseudoaldosteronism or hypokalemia or current use of potassium supplementation 5. Screening potassium level 3.4 mEq/L or less 6. Screening diastolic blood pressure (DBP) more than 90 mmHg or systolic blood pressure (SBP) more than 150 mmHg after sufficient rest 7. Screening albumin below normal laboratory level either at the Columbia or Mayo Clinic Jacksonville Laboratory 8. Screening bicarbonate or carbon dioxide level greater than 29 mmol/L, suggesting metabolic alkalosis 9. Screening sodium level greater than 145 mmol/L, suggesting hypernatremia 10. Unstable or active medical or neurological (other than ALS) diseases which require treatment 11. Failure of the Capacity Assessment [38] 12. Not able and/or willing to comprehend and sign the informed consent 13. Not able to speak or write English to complete the primary outcome measure, the MCS 14. Taking any experimental medication or unapproved medications directed at treating muscle cramps 15. Those who are pregnant or breastfeeding 16. Those who have renal or hepatic impairment