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| Name | Class |
|---|---|
| Tsumura & Co., Tokyo, Japan | UNKNOWN |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hiroshi Mistumoto, MD, Dsc. | Columbia University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Scottsdale | Arizona | 85259 | United States | ||
| Mayo Clinic |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37430314 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 will be randomized to the following treatment sequences: TJ-68, placebo, placebo, TJ-68 (1 week WO between each treatment period) |
| FG001 | 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 will be randomized to the following treatment sequences: placebo, TJ-68, TJ-68, placebo (1 week WO between each treatment period) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment (2 Weeks) |
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| Washout (1 Week) |
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| Treatment (2 Weeks) |
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| Washout (1 Week) |
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| Treatment (2 Weeks) |
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| Washout (1 Week) |
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| Treatment (2 Weeks) |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 will be randomized to the following treatment sequences: TJ-68, placebo, placebo, TJ-68 (1 week WO between each treatment period) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | score on a scale | Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported |
|
11 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants who were administered the placebo during the first 2-week treatment period. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Respiratory distress due to RSV | Infections and infestations | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Facial rash | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Hiroshi Mitsumoto, MD | Columbia University | 212-305-1319 | hm264@cumc.columbia.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 27, 2024 | Mar 24, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| D009120 | Muscle Cramp |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
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| ID | Term |
|---|---|
| C038462 | shakuyaku-kanzoh-toh |
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|
| 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. |
|
|
| Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported |
| 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. | Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported |
| 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. | Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported |
| 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. | Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported |
| 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. | Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported |
| 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. | Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported |
| Jacksonville |
| Florida |
| 32224 |
| United States |
| Columbia University Irving Medical Center | New York | New York | 10032 | United States |
| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
|
| BG001 | 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 will be randomized to the following treatment sequences: placebo, TJ-68, TJ-68, placebo (1 week WO between each treatment period) |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| TJ-68 |
Participants who were administered TJ-68 during the first 2-week treatment period. |
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Assessed at Baseline, Week 2, Week 5, Week 8 and Week 11; Week 2 reported |
|
|
|
| 0 |
| 11 |
| 0 |
| 11 |
| 3 |
| 11 |
| EG001 | TJ-68 | Participants who were administered TJ-68 during the first 2-week treatment period. | 0 | 11 | 2 | 11 | 5 | 11 |
| Diverticulitis with pericecal abscess | Gastrointestinal disorders | Systematic Assessment |
|
| Abdominal bloating | Gastrointestinal disorders | Systematic Assessment |
|
| Stomachache | Gastrointestinal disorders | Systematic Assessment |
|
| Elevated blood pressure | General disorders | Systematic Assessment |
|
| Flu-like symptoms | General disorders | Systematic Assessment |
|
| Joint pain | General disorders | Systematic Assessment |
|
| Scleral erythema | Eye disorders | Systematic Assessment |
|
| COVID-19 | Infections and infestations | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Sinusitis | General disorders | Systematic Assessment |
|
| Hypertension | General disorders | Systematic Assessment |
|
| Fall | General disorders | Systematic Assessment |
|
| Hypokalemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Rash acneiform | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Urinary frequency | Renal and urinary disorders | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
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| D019636 | Neurodegenerative Diseases |
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |