Mexiletine for the Treatment of Muscle Cramps in ALS

• ClinicalTrials.gov Identifier: NCT01811355
• Recruitment Status: Completed
• First Posted: March 14, 2013
• Results First Posted: June 27, 2017
• Last Update Posted: August 28, 2017
• Sponsor: Bjorn Oskarsson, MD
• Collaborators: University of California, Davis; ALS Association
• Information provided by (Responsible Party): Bjorn Oskarsson, MD, University of California, Davis

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Muscle Cramps in Amyotrophic Lateral Sclerosis
• Interventions: Drug: Mexiletine; Drug: Placebo
• Enrollment: 23

Participant Flow

Recruitment Details
Pre-assignment Details	Of 28 patients who signed consent, 5 did not meet inclusion criteria because of past myocardial infarction (n=1), long QT syndrome (n=1), AV block (n=1), no muscle cramps (n=1), and hospitalization during the screening period that resulted in inability to complete a screening diary and follow-up (n=1) .

Arm/Group Title	Mexiletine First/Placebo Second	Placebo First/Mexiletine Second
Arm/Group Description	Mexiletine, capsule, 150mg, PO BID, 14 days Placebo, capsule, PO BID, 14 days	Placebo, capsule, PO BID, 14 days Mexiletine, capsule, 150mg, PO BID, 14 days
Period Title: First Dose
Started	11	12
Completed	9	12
Not Completed	2	0
Period Title: Washout
Started	9	12
Completed	9	12
Not Completed	0	0
Period Title: Second Dose
Started	9	12
Completed	9	12
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Total Subjects Enrolled
Arm/Group Description		A total of 23 subjects were enrolled. 11 were randomized to receive study drug first, followed by placebo. 12 subjects received placebo first and study drug second. Overall participant characteristics are displayed in the baseline table.
Overall Number of Baseline Participants		23
Baseline Analysis Population Description		[Not Specified]
Age, Customized; Mean (Standard Deviation); Unit of measure: Years
Years	Number Analyzed	23 participants
		62.4 (12.5)
Sex/Gender, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	23 participants
males		15 65.2%
females		8 34.8%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	23 participants
	Hispanic or Latino	3 13.0%
	Not Hispanic or Latino	20 87.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	23 participants
	American Indian or Alaska Native	0 0.0%
	Asian	1 4.3%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	22 95.7%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	23 participants
		23

Outcome Measures

1. Primary Outcome

Title	Daily Muscle Cramps
Description	The average of the daily recording of number of muscle cramps that occurred in the last 24 hours- over a 6 week period.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Among the 21 patients who completed the study, 1 patient did not return the outcome diary, which resulted in 20 patients available for analysis.

Arm/Group Title	Mexiletine First/Placebo Second	Placebo First/Mexiletine Second
Arm/Group Description:	Mexiletine, capsule, 150mg, PO BID, 14 days Placebo, capsule, PO BID, 14 days	Placebo, capsule, PO BID, 14 days Mexiletine, capsule, 150mg, PO BID, 14 days
Overall Number of Participants Analyzed	8	12
Mean (Standard Deviation); Unit of Measure: Cramps per 24 hours
Placebo Dose	6.1 (8.1)	4.7 (4.2)
Mexiletine Dose	4.9 (8.0)	2.5 (2.8)
Difference Between	1.2 (2.9)	2.2 (2.2)

2. Primary Outcome

Title	Cramp Severity
Description	Daily cramp severity was rated on the 100-unit visual analog scale. Scores ranged from 0 to 100, with 100 being the greatest amount of cramp severity
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Among the 21 patients who completed the study, 1 patient did not return the outcome diary, which resulted in 20 patients available for analysis.

Arm/Group Title	Mexiletine First	Placebo First
Arm/Group Description:	Mexiletine, capsule, 150mg, PO BID, 14 days Mexiletine: Sodium channel blocker	Placebo, capsule, PO BID, 14 days Placebo: Placebo
Overall Number of Participants Analyzed	8	12
Mean (Standard Deviation); Unit of Measure: units on a scale
Placebo Dose	43.6 (31.0)	44.7 (26.7)
Mexiletine Dose	23.1 (16.8)	32.8 (27.7)
Difference Between	20.5 (40.6)	12.0 (18.1)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Mexiletine		Placebo
Arm/Group Description	Mexiletine, capsule, 150mg, PO BID, 14 days Mexiletine: Sodium channel blocker		Placebo, capsule, PO BID, 14 days Placebo: Placebo
All-Cause Mortality
	Mexiletine		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/23 (0.00%)		0/21 (0.00%)
Serious Adverse Events
	Mexiletine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0.00%)		0/21 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Mexiletine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/23 (39.13%)		3/21 (14.29%)
Ear and labyrinth disorders
Congestion * [1]	0/23 (0.00%)	0	1/21 (4.76%)	1
Gastrointestinal disorders
Dry mouth * [1]	1/23 (4.35%)	1	0/21 (0.00%)	0
Nausea * [1]	1/23 (4.35%)	1	0/21 (0.00%)	0
Diarrhea * [1]	1/23 (4.35%)	1	0/21 (0.00%)	0
Nervous system disorders
Dizzines * [1]	1/23 (4.35%)	1	0/21 (0.00%)	0
Fall †	1/23 (4.35%)	1	1/21 (4.76%)	1
Headache * [1]	1/23 (4.35%)	1	1/21 (4.76%)	1
Renal and urinary disorders
Increased urination * [1]	1/23 (4.35%)	1	0/21 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Chest tightness * [1]	1/23 (4.35%)	1	0/21 (0.00%)	0
Skin and subcutaneous tissue disorders
Itchiness * [1]	1/23 (4.35%)	1	0/21 (0.00%)	0
* Indicates events were collected by non-systematic assessment; [1] Mild; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Bjorn Oskarsson
• Organization: Mayo Clinic, Jacksonville
• Phone: 9049536896
• EMail: oskarsson.bjorn@mayo.edu

• Responsible Party: Bjorn Oskarsson, MD, University of California, Davis
• ClinicalTrials.gov Identifier: NCT01811355
• Other Study ID Numbers: 378164
• First Submitted: March 6, 2013
• First Posted: March 14, 2013
• Results First Submitted: April 3, 2017
• Results First Posted: June 27, 2017
• Last Update Posted: August 28, 2017