TJ-68 Clinical Trial in Patients With Amyotrophic Lateral Sclerosis (ALS) and Muscle Cramps

NCT04998305 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: AAAT0610
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

Brief Summary

The primary objective of the study is to demonstrate the safety and potential efficacy of TJ-68 for improving muscle cramps in participants with ALS based on a two-site, randomized, placebo-controlled double-blind multi-period crossover (N-of-1) study design.

Conditions

Amyotrophic Lateral Sclerosis; Muscle Cramp

Outcome Measures

Primary Outcomes (1)

• Visual Analog Scale (MCS-VAS) Score

  This is designed to measure improvements in muscle cramps. MCS-VAS indicates the level to which muscle cramps affect overall daily activity. The score ranges from 0 to 10; 0 indicates no interference and 10 indicates severe interference with overall daily activity. MCS-VAS will be administered by a trained evaluator to reduce recall bias and lack of insight, which can limit subjective assessments. To minimize carryover effects, results reflect the average of the scores taken at the second week of each treatment period.

  Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported

Secondary Outcomes (6)

• Overall Muscle Cramp Scale (MCS) Score

  Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported

• Self-reported Cramp Pain Score

  Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported

• ALSFRS-R Score

  Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported

• Clinical Global Impression of Changes (CGIC) Score

  Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported

• ALSAQ-5 (Quality of Life Questionnaire) Score

  Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported

Study Arms (2)

Treatment sequence TJ-68-Placebo-Placebo-TJ-68

EXPERIMENTAL

Employing an N-of-1, crossover design, each participant in the TJ-68 clinical trial will serve as his/her control. The participation will last for 11 weeks - four, 2-week treatment periods with 1-week washout (WO) period between each treatment period. Participants (n=13) will be randomized to the following treatment sequences: TJ-68, placebo, placebo, TJ-68 (1 week WO between each treatment period)

Drug: TJ-68; Drug: Placebo

Treatment sequence Placebo-TJ-68-TJ-68-Placebo

EXPERIMENTAL

Employing an N-of-1, crossover design, each participant in the TJ-68 clinical trial will serve as his/her control. The participation will last for 11 weeks - four, 2-week treatment periods with 1-week washout (WO) period between each treatment period. Participants (n=13) will be randomized to the following treatment sequences: placebo, TJ-68, TJ-68, placebo (1 week WO between each treatment period)

Drug: TJ-68; Drug: Placebo

Interventions

TJ-68 DRUG

For two periods (one period = 2 weeks) during the 11-week participation, participants will take 2.5 g of TJ-68 for three times per day before meals. It will be administered by dissolving 2.5 g of TJ-68 powder in 1 oz. of lukewarm water.

Also known as: Shakuyakukanzoto

Treatment sequence Placebo-TJ-68-TJ-68-Placebo; Treatment sequence TJ-68-Placebo-Placebo-TJ-68

Placebo DRUG

For two periods (one period = 2 weeks) during the 11-week participation, participants will take 2.5 g of placebo for three times per day before meals. It will be administered by dissolving 2.5 g of the placebo powder in 1 oz. of lukewarm water.

Also known as: Placebo Tablet

Treatment sequence Placebo-TJ-68-TJ-68-Placebo; Treatment sequence TJ-68-Placebo-Placebo-TJ-68

Eligibility Criteria

• Age: 20 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Experiences at least one muscle cramp in any muscle per day
• Age 20 to 84 years old
• Forced vital capacity is 45% of normal or greater in a seated position
• Able to swallow liquid via the mouth or be given via a feeding tube
• 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
• Able to comprehend and willing to give (sign) the informed consent
• Willing to commute to the study site for the frequent visits, including a screening visit (study visits at the end of week 2, 5, 8 and 11)
• Taking a stable dose of Riluzole (Rilutek), Edaravone (Radicava), and/or sodium phenylbutyrate/taurursodiol (Relyvrio) for at least a month before randomization and not expected to require dose titration or initiation of these medications during the study period
• Willing to discontinue over-the-counter (OTC) products containing any peony root, Glycyrrhiza, or both
• Willing to discontinue Mexiletine, Quinine sulfate, or Ranolazine during the study period
• Willing to avoid food, beverages, and medications that may induce or inhibit metabolism of enzyme of transporters.
• 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).
• Willing to practice contraceptive measures for male and female patients.

You may not qualify if:

• History of allergic reactions to peony root, Glycyrrhiza, or FD\&C Yellow No. 5 (tartrazine)
• 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)
• History of pseudoaldosteronism or hypokalemia or current use of potassium supplementation
• Screening potassium level 3.4 mEq/L or less
• Screening diastolic blood pressure (DBP) more than 90 mmHg or systolic blood pressure (SBP) more than 150 mmHg after sufficient rest
• Screening albumin below normal laboratory level either at the Columbia or Mayo Clinic laboratory
• Screening bicarbonate or carbon dioxide level less than 29 mmol/L, suggesting metabolic alkalosis
• Screening sodium level greater than 145 mmol/L, suggesting hypernatremia
• Unstable or active medical or neurological (other than ALS) diseases which require treatment
• Failure of Capacity Assessment
• Not able and/or willing to comprehend and sign the informed consent
• Not able to speak or write English to complete the primary outcome measure, MCS
• Taking any experimental medication or unapproved medications directed at treating muscle cramps
• Those who are pregnant or breast feeding
• Those who have renal or hepatic impairment

Sponsors & Collaborators

• Hiroshi Mitsumoto: lead
• Tsumura & Co., Tokyo, Japan: collaborator

Study Sites (3)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Related Publications (1)

• Mitsumoto H, Cheung K, Oskarsson B, Andrews HF, Jang GE, Andrews JA, Shah JS, Fernandes JA, McElhiney M, Santella RM. Randomized double-blind personalized N-of-1 clinical trial to test the safety and potential efficacy of TJ-68 for treating muscle cramps in amyotrophic lateral sclerosis (ALS): study protocol for a TJ-68 trial. Trials. 2023 Jul 10;24(1):449. doi: 10.1186/s13063-023-07424-8.

  PMID: 37430314 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Muscle Cramp

Interventions

shakuyaku-kanzoh-toh

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Hiroshi Mitsumoto, MD
• Organization: Columbia University

hm264@cumc.columbia.edu

212-305-1319

Study Officials

• Hiroshi Mistumoto, MD, Dsc.

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Wesley J. Howe Professor of Neurology

Study Record Dates

• First Submitted: July 21, 2021
• First Posted: August 10, 2021
• Study Start: September 30, 2022
• Primary Completion: July 26, 2024
• Study Completion: July 26, 2024
• Last Updated: May 1, 2025
• Results First Posted: May 1, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)