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

Primary Purpose

Amyotrophic Lateral Sclerosis, Muscle Cramp

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

TJ-68

Placebo

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis

Eligibility Criteria

20 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 70 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), or both 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 Jacksonville laboratory
Screening bicarbonate or carbon dioxide level less than 19 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

Sites / Locations

Mayo ClinicRecruiting
Columbia University Irving Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

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

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

Arm Description

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)

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)

Outcomes

Primary Outcome Measures

Change in 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.

Secondary Outcome Measures

Change in 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. All of the MCS components will be administered by a trained evaluator and evaluated by investigator.

Change in self-reported cramp pain score

Participants will complete weekly cramp diary and cramp pain scale. Cramp diary will assess frequency (0 to more than 10 cramps) and severity (mild, moderate, severe) of muscle cramps in various parts of the body (R/L leg, arm; torso; neck or above). Cramp pain will be measured on a scale of 0 to 10 with 0 indicating no pain and 10 indicating severe pain.

Change in 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.

Change in Clinical Global Impression of Changes (CGIC) Score

Changes in participant's feelings since the start of dosing will measured by using a score of 1 to 7 with 1 indicating "very much improved" and 7 indicating "very much worse."

Change in ALSAQ-5 (Quality of Life Questionnaire) Score

Changes in 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.

Change in 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."

Full Information

NCT ID

NCT04998305

First Posted

July 21, 2021

Last Updated

October 12, 2022

Sponsor

Hiroshi Mitsumoto

Collaborators

Tsumura & Co., Tokyo, Japan

1. Study Identification

Unique Protocol Identification Number

NCT04998305

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

September 30, 2022 (Actual)

Primary Completion Date

October 2023 (Anticipated)

Study Completion Date

October 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Hiroshi Mitsumoto

Collaborators

Tsumura & Co., Tokyo, Japan

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis, Muscle Cramp

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

26 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

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)

Intervention Type

Drug

Intervention Name(s)

TJ-68

Other Intervention Name(s)

Shakuyakukanzoto

Intervention Description

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

Intervention Name(s)

Placebo

Other Intervention Name(s)

Placebo Tablet

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in Visual Analog Scale (MCS-VAS) Score

Description

Time Frame

Baseline, Week 2, Week 5, Week 8 and Week 11

Secondary Outcome Measure Information:

Title

Change in overall Muscle Cramp Scale (MCS) Score

Description

Time Frame

Baseline, Week 2, Week 5, Week 8 and Week 11

Title

Change in self-reported cramp pain score

Description

Time Frame

Baseline, Week 2, Week 5, Week 8 and Week 11

Title

Change in ALSFRS-R Score

Description

Time Frame

Baseline, Week 2, Week 5, Week 8 and Week 11

Title

Change in Clinical Global Impression of Changes (CGIC) Score

Description

Changes in participant's feelings since the start of dosing will measured by using a score of 1 to 7 with 1 indicating "very much improved" and 7 indicating "very much worse."

Time Frame

Baseline, Week 2, Week 5, Week 8 and Week 11

Title

Change in ALSAQ-5 (Quality of Life Questionnaire) Score

Description

Time Frame

Baseline, Week 2, Week 5, Week 8 and Week 11

Title

Change in Goal Attainment Scale (GAS) Score

Description

Time Frame

Baseline, Week 2, Week 5, Week 8 and Week 11

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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 70 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), or both 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 Jacksonville laboratory Screening bicarbonate or carbon dioxide level less than 19 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Hiroshi Mistumoto, MD, Dsc.

Phone

212-305-1319

hm264@cumc.columbia.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Grace Jang, BA

Phone

212-305-7037

gej2116@cumc.columbia.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hiroshi Mistumoto, MD, Dsc.

Organizational Affiliation

Columbia University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32224

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Bjorn E Oskarsson, MD

Phone

904-953-2903

oskarsson.bjorn@mayo.edu

First Name & Middle Initial & Last Name & Degree

Colette McHugh-Strong, JD, CRC

Phone

904-953-4965

mchugh-strong.colette@mayo.edu

First Name & Middle Initial & Last Name & Degree

Bjorn E Oskarsson, MD

First Name & Middle Initial & Last Name & Degree

Jaimin S Shah, MD

Facility Name

Columbia University Irving Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hiroshi Mitsumoto, MD, DSc.

Phone

212-305-1319

hm264@cumc.columbia.edu

First Name & Middle Initial & Last Name & Degree

Grace Jang, BA

Phone

212-305-7037

gej2116@cumc.columbia.edu

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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