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

NCT ID: NCT04998305

Last Updated: 2025-05-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-30
• Study Completion Date: 2024-07-26

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.

Detailed Description

In Japan, TJ-68 is a common Kampo medicine prescribed by Japanese physicians to manage muscle cramps or pain of diverse origins. In the USA, there are no effective medications to control muscle cramps and no approved medications to specifically treat muscle cramps. Quinine sulfate and Mexiletine have shown some effect with additional safety considerations. The fact that TJ-68 has been commonly used for the treatment of muscle cramps in Japan and the lack of available medications for cramps in ALS represent the fundamental rationale for this proposal.

This is a phase 1/2, two-site, double-blinded, randomized, placebo-controlled, multi-period crossover clinical trial for individuals with ALS and muscle cramps. Participants will be enrolled in the study for 11 weeks and receive TJ-68, also known as Shakuyakukanzoto - a kampo, herbal medicine - to assess its effect in relieving muscle cramps. This clinical trial employs N-of-1 study design in which all participants will receive TJ-68 and placebo at certain points, serving as their own controls.

Conditions

Amyotrophic Lateral Sclerosis; Muscle Cramp

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

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)

Group Type: EXPERIMENTAL

TJ-68

Intervention Type: 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.

Placebo

Intervention Type: 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.

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

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)

Group Type: EXPERIMENTAL

TJ-68

Intervention Type: 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.

Placebo

Intervention Type: 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.

Interventions

TJ-68

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

Shakuyakukanzoto; Placebo Tablet

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 84 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tsumura & Co., Tokyo, Japan

UNKNOWN

Sponsor Role: collaborator

Hiroshi Mitsumoto

OTHER

Sponsor Role: lead

Responsible Party

Hiroshi Mitsumoto

Wesley J. Howe Professor of Neurology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Hiroshi Mistumoto, MD, Dsc.

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Mayo Clinic

Scottsdale, Arizona, United States

Mayo Clinic

Jacksonville, Florida, United States

Columbia University Irving Medical Center

New York, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37430314 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

AAAT0610

Identifier Type: -

Identifier Source: org_study_id