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Amyotrophic Lateral SclerosisPhase 1/2NCT04998305

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

A Phase 1/2 study testing TJ-68 in people with Amyotrophic Lateral Sclerosis and Muscle Cramp, run by Hiroshi Mitsumoto at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 20 to 84 years
Conditions the study is for
Amyotrophic Lateral Sclerosis, Muscle Cramp
What is being tested?
TJ-68
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
11 participants
Where
3 sitesUnited States
Study dates
30 Sep 2022to 26 Jul 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 84 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • Columbia University Irving Medical Center

    New York, New York, 10032

  • Mayo Clinic

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: A Phase 1/2 Two-center, Double-blind, Randomized, Placebo-controlled Multi-period Crossover (N-of-1) Study to Evaluable the Feasibility, Safety, and Efficacy of TJ-68 in Patients With Amyotrophic Lateral Sclerosis (ALS) and Muscle Cramps

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.

Read the 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.

Being tested
TJ-68, Placebo
Medical subject headings
Amyotrophic Lateral Sclerosis, Muscle Cramp

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TJ-68Drug

    Also called Shakuyakukanzoto

    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.

  • PlaceboDrug

    Also called Placebo Tablet

    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.

Study groups in NCT04998305
Study groupRoleWhat they receive
Treatment sequence TJ-68-Placebo-Placebo-TJ-68ExperimentalEmploying 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)
Receives: Drug: TJ-68; Drug: Placebo
Treatment sequence Placebo-TJ-68-TJ-68-PlaceboExperimentalEmploying 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)
Receives: Drug: TJ-68; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (6)

  1. Overall Muscle Cramp Scale (MCS) Score

    Changes in trigger, frequency, severity, and location of muscle cramps will be measured by administering all of MCS questions. Motor behaviors which trigger muscle cramps and muscle cramps' effects on sleep quality will also be measured. The score for each component of MCS -- trigger, frequency, severity, location, behavior, and effect on sleep quality -- will range from 1 to 5, with the severity increasing from 1 to 5. The total score range is 6 to 30. All of the MCS components will be administered by a trained evaluator and evaluated by the investigator. To minimize carryover effects, results reflect the average of the scores taken at the second week of each treatment period.

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

  2. Self-reported Cramp Pain Score

    Cramp pain will be measured on a scale of 0 to 10 with 0 indicating no pain and 10 indicating severe pain. To minimize carryover effects, results reflect the average of the scores taken at the second week of each treatment period.

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

  3. ALSFRS-R Score

    Changes in functionality due to disease progression will be measured by administering ALSFRS-R to participants. ALSFRS-R includes 12 questions that can have a score of 0 to 4. A score of 0 on a question would indicate no function while a score of 4 would indicate full function. Total score range is 0 to 48. To minimize carryover effects, results reflect the average of the scores taken at the second week of each treatment period.

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

  4. Clinical Global Impression of Changes (CGIC) Score

    Changes in participant's feelings since the start of dosing will be measured by using a score of 1 to 7 with 1 indicating "very much improved" and 7 indicating "very much worse." To minimize carryover effects, results reflect the average of the scores taken at the second week of each treatment period.

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

  5. ALSAQ-5 (Quality of Life Questionnaire) Score

    Participants' motor functions and resulting quality of life will be measured by asking questions about their ability to perform certain tasks or feelings of hopelessness within the last two weeks. Participants can answer by saying never, rarely, sometimes, often, or always/cannot do at all. The ALSAQ-5 full score range is from 0 to 100, with 0 reflecting the best health state. To minimize carryover effects, results reflect the average of the scores taken at the second week of each treatment period.

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

  6. Goal Attainment Scale (GAS) Score

    Participant and the evaluator will collaborate and establish a goal. Progression of goal achievement will be measured over the course of participation and scored from -2 to +2 with -2 indicating "(achievement) much worse than expected" and +2 indicating "(achievement) much better than expected." To minimize carryover effects, results reflect the average of the scores taken at the second week of each treatment period.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2021
  2. Study start30 Sep 2022
  3. Primary completion26 Jul 2024
  4. Study completion26 Jul 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04998305
Sponsor's protocol ID
AAAT0610
Status last verified
Apr 2025
First submitted
21 Jul 2021
Last updated
1 May 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37430314

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TJ-68 in people with Amyotrophic Lateral Sclerosis and Muscle Cramp, run by Hiroshi Mitsumoto at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Visual Analog Scale (MCS-VAS) Score (time frame: Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04998305, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2025.

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