Trial · NCT02781454

Mexiletine in Sporadic Amyotrophic Lateral Sclerosis

NCT02781454, Phase 2, Completed, University of Washington; results first posted 2019-12-05

3 sourcestrials-2026-11-12-0.5.0

Cite this record

ConductScience Library. Mexiletine in Sporadic Amyotrophic Lateral Sclerosis. Trials, record NCT02781454. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02781454

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Mexiletine in Sporadic Amyotrophic Lateral Sclerosis
NCT number: NCT02781454
Status: Completed
Phases: Phase 2
Enrollment: 20 participants, actual
Lead sponsor: University of Washington
Conditions: Sporadic Amyotrophic Lateral Sclerosis
Interventions: Mexiletine, Placebo
First posted: 2016-05-24
Last updated: 2019-12-05
Results first posted: 2019-12-05

Source ClinicalTrials.gov

Registered outcomes13

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Change in Resting Motor Threshold	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 and from Week 4 to Week 8 reported	The resting motor threshold (RMT) assessed from single pulse transcranial magnetic stimulation (TMS) measurements made before treatment, after 4 weeks of treatment, and then again after a 4 week washout, was used as the primary pharmacodynamic marker of cortical hyperexcitability. RMT is the stimulus intensity required to produce and maintain a 0.2 mV peak-to-peak motor evoked potential of the abductor pollicis brevis muscle by TMS. A smaller RMT is thought to suggest greater neuronal excitability.
Secondary	Effect on Short-interval Intracortical Inhibition	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported	Short-interval intracortical inhibition (SICI) is a measure of neuronal excitability measured by dual pulse TMS with a conditioned (80% of RMT) and test pulses (120% of RMT) to generate a stable MEP amplitude of 0.2 mV, averaged over interstimulus intervals of 1-7 ms. It is thought to reflect refractory cortical axons and subsequent resynchronization of cortico-cortical and corticomotoneuronal volleys or activation of non-GABAergic cortical inhibitory circuits (initial phase) and synaptic neurotransmission through GABAA receptors (second phase). The value for SICI thought to be maximally sensitive for detecting in changes in ALS subjects compared to controls is is derived by measuring the motor evoked potential amplitude (MEP) at an interstimulus interval of 3 ms (ISI 3 ms) and normalizing to the MEP amplitude at 120% of the resting motor threshold (MEP 120% RMT). A reduction in SICI reflecting greater excitability would generate a larger ratio of MEP ISI 3 ms/MEP 120% RMT.
Secondary	Change in Motor Evoked Potential Amplitude	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported	The motor evoked potential (MEP) amplitude is taken from single pulse transcranial magnetic stimulation (TMS) and reflects the density of corticomotoneuronal projections onto motor neurons and is affected by cortical hyperexcitability early in ALS where it is thought to be larger than age-matched controls and axonal degeneration later in the disease when it decreases in amplitude. The MEP is most reliable in assessing cortical motor neuronal preservation and excitability when normalized to the peak compound nerve action potential (CMAP) amplitude which reflects the integrity of peripheral motor nerve axons. It is also normalized here to 120% of the RMT to derive a ratio of MEP at 120% RMT/peak CMAP.
Secondary	Effect on Cortical Silent Period	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported	The cortical silent period (CSP) is recorded with single pulse TMS as a duration from the onset of the MEP response to resumption of voluntary electromyography activity with the patient performing a voluntary contraction, set to 30% of maximal voluntary contraction. A shorter CSP compared to controls would reflect greater excitability.
Secondary	Effect on Strength Duration Time Constant	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported	The strength duration time constant (SDTC) is used in threshold tracking nerve axonal excitability studies and is interpreted as a measure of axonal excitability that is dependent upon the biophysical properties of the axonal membrane at the node of Ranvier, especially persistent sodium current. It is derived from the relationship between stimulus duration and intensity. A higher SDTC would reflect greater excitability of motor nerve axons.
Secondary	Effect on Depolarizing Threshold Electrotonus (90-100 ms)	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported	Depolarizing threshold electrotonus (90-100 ms) (TEd 90-100 ms) is used in threshold tracking nerve axonal excitability studies in which long-lasting subthreshold depolarizing currents are generated, measured at 90-100 ms following the stimulus. This measure is associated with a decrease in the membrane excitability threshold due to opening of potassium channels on the axonal membrane. Intrinsic changes in axonal excitability properties, such as thought to occur in ALS, could possibly alter this measure, presumably by decreasing TEd 90-100 ms more substantially than normal.
Secondary	Effect on Hyperpolarizing Threshold Electrotonus (90-100 ms)	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported	Hyperpolarizing threshold electrotonus (90-100 ms) (TEh 90-100 ms) is used in threshold tracking nerve axonal excitability studies in which long-lasting subthreshold hyperpolarizing currents are generated, measured at 90-100 ms following the stimulus. This measure is associated with an increase in the membrane excitability threshold due to closure of potassium channels causing increased resistance of the internodal axonal membrane. Intrinsic changes in axonal excitability properties, such as thought to occur in ALS, could possibly alter this measure.
Secondary	Effect on Superexcitability	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported	Superexcitability is a component of recovery cycle analysis assessing motor axonal excitability, employing threshold tracking nerve conduction study. It is a depolarizing afterpotential measured following a single supramaximal stimulus followed by a second smaller stimulus of variable intensity and reflects passive depolarization of the internodal axon.
Secondary	Effect on Subexcitability	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported	Subexcitability is a component of recovery cycle analysis assessing motor axonal excitability, employing threshold tracking nerve conduction study. It is a late hyperpolarizing after potential measured following a single supramaximal stimulus followed by a second smaller stimulus of variable intensity and is related to the very slow turn-off of slow potassium channels.
Secondary	Effect on Frequency of Muscle Cramps	Accessed at Screening, Baseline, Week 4, and Week 8; comparisons of treatments at Weeks 3-4 reported	Will be assessed using a daily muscle cramps diary tabulated weekly beginning at Baseline.

1 to 10 of 13Source ClinicalTrials.gov

See all 13 registered outcomes

Outcomes13

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Change in Resting Motor Threshold	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 and from Week 4 to Week 8 reported		percentage of maximum stimulus output	LEAST_SQUARES_MEAN
SECONDARY	Effect on Short-interval Intracortical Inhibition	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported		unitless ratio MEP ISI 3 ms/MEP 120% RMT	GEOMETRIC_LEAST_SQUARES_MEAN
SECONDARY	Change in Motor Evoked Potential Amplitude	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported	MEP at 120% RMT/peak CMAP	unitless ratio of ms/ms	GEOMETRIC_LEAST_SQUARES_MEAN
SECONDARY	Effect on Cortical Silent Period	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported		milliseconds	LEAST_SQUARES_MEAN
SECONDARY	Effect on Strength Duration Time Constant	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported	strength duration time constant	milliseconds	GEOMETRIC_LEAST_SQUARES_MEAN
SECONDARY	Effect on Depolarizing Threshold Electrotonus (90-100 ms)	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported		percentage of threshold depolarization	LEAST_SQUARES_MEAN
SECONDARY	Effect on Hyperpolarizing Threshold Electrotonus (90-100 ms)	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported		percentage threshold hyperpolarization	LEAST_SQUARES_MEAN
SECONDARY	Effect on Superexcitability	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported		percentage of threshold change	LEAST_SQUARES_MEAN
SECONDARY	Effect on Subexcitability	Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported		percentage of threshold change	LEAST_SQUARES_MEAN
SECONDARY	Effect on Frequency of Muscle Cramps	Accessed at Screening, Baseline, Week 4, and Week 8; comparisons of treatments at Weeks 3-4 reported		muscle cramps/week	GEOMETRIC_LEAST_SQUARES_MEAN

1 to 10 of 13Source ClinicalTrials.gov

See all 13 outcomes

Results by group42

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Spread	Units
Change in Resting Motor Threshold	Mexiletine, 300 Milligrams	change from baseline to week 4	-2.430	Standard Error 2.323	percentage of maximum stimulus output
Change in Resting Motor Threshold	Mexiletine, 600 Milligrams	change from baseline to week 4	0.805	Standard Error 2.207	percentage of maximum stimulus output
Change in Resting Motor Threshold	Placebo	change from baseline to week 4	4.746	Standard Error 2.185	percentage of maximum stimulus output
Change in Resting Motor Threshold	Mexiletine, 300 Milligrams	change from week 4 to week 8	1.465	Standard Error 2.357	percentage of maximum stimulus output
Change in Resting Motor Threshold	Mexiletine, 600 Milligrams	change from week 4 to week 8	-0.284	Standard Error 2.169	percentage of maximum stimulus output
Change in Resting Motor Threshold	Placebo	change from week 4 to week 8	-2.908	Standard Error 2.247	percentage of maximum stimulus output
Effect on Short-interval Intracortical Inhibition	Mexiletine, 300 Milligrams		0.655	95% Confidence Interval 0.437 to 0.983	unitless ratio MEP ISI 3 ms/MEP 120% RMT
Effect on Short-interval Intracortical Inhibition	Mexiletine, 600 Milligrams		0.886	95% Confidence Interval 0.608 to 1.291	unitless ratio MEP ISI 3 ms/MEP 120% RMT
Effect on Short-interval Intracortical Inhibition	Placebo		0.961	95% Confidence Interval 0.634 to 1.459	unitless ratio MEP ISI 3 ms/MEP 120% RMT
Change in Motor Evoked Potential Amplitude	Mexiletine, 300 Milligrams		0.589	95% Confidence Interval 0.315 to 1.102	unitless ratio of ms/ms

1 to 10 of 42Source ClinicalTrials.gov

See all 42 results by group

Participant flow9

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Mexiletine, 300 Milligrams	8
Overall Study	STARTED	Mexiletine, 600 Milligrams	6
Overall Study	STARTED	Placebo	6
Overall Study	COMPLETED	Mexiletine, 300 Milligrams	8
Overall Study	COMPLETED	Mexiletine, 600 Milligrams	6
Overall Study	COMPLETED	Placebo	5
Overall Study	NOT COMPLETED	Mexiletine, 300 Milligrams	0
Overall Study	NOT COMPLETED	Mexiletine, 600 Milligrams	0
Overall Study	NOT COMPLETED	Placebo	1

Source ClinicalTrials.gov

Adverse events87

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events
other	Inner ear signs and symptoms	Ear and labyrinth disorders	Mexiletine, 300 Milligrams	0	8	0
other	Inner ear signs and symptoms	Ear and labyrinth disorders	Mexiletine, 600 Milligrams	1	6	1
other	Inner ear signs and symptoms	Ear and labyrinth disorders	Placebo	0	6	0
other	Dental pain and sensation disorders	Gastrointestinal disorders	Mexiletine, 300 Milligrams	1	8	1
other	Dental pain and sensation disorders	Gastrointestinal disorders	Mexiletine, 600 Milligrams	0	6	0
other	Dental pain and sensation disorders	Gastrointestinal disorders	Placebo	0	6	0
other	Diarrhoea (excl infective)	Gastrointestinal disorders	Mexiletine, 300 Milligrams	0	8	0
other	Diarrhoea (excl infective)	Gastrointestinal disorders	Mexiletine, 600 Milligrams	1	6	1
other	Diarrhoea (excl infective)	Gastrointestinal disorders	Placebo	0	6	0
other	Dyspeptic signs and symptoms	Gastrointestinal disorders	Mexiletine, 300 Milligrams	1	8	1

1 to 10 of 87Source ClinicalTrials.gov

See all 87 adverse events

Adverse event totals9

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Mexiletine, 300 Milligrams	0	8
Total, all-cause mortality	Mexiletine, 600 Milligrams	0	6
Total, all-cause mortality	Placebo	0	6
Total, other adverse events	Mexiletine, 300 Milligrams	5	8
Total, other adverse events	Mexiletine, 600 Milligrams	5	6
Total, other adverse events	Placebo	5	6
Total, serious adverse events	Mexiletine, 300 Milligrams	0	8
Total, serious adverse events	Mexiletine, 600 Milligrams	0	6
Total, serious adverse events	Placebo	1	6

Source ClinicalTrials.gov

Papers0

The papers the trial lists on ClinicalTrials.gov.

None in this release.

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons0

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

None in this release.

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

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