Effects of Mexiletine on Colonic Transit in a Patient With Irritable Bowel Syndrome - Constipation (IBS-C)

Study Overview
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Brief Summary
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To understand if Mexiletine will restores normal colonic motility in a patient with irritable bowel syndrome - constipation (IBS-C) and a genetic mutation in SCN5A.

Detailed Description
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To understand if Mexiletine will restore normal colonic motility in a patient with a missense mutation in SCN5A, which encodes a voltage-sensitive sodium channel NaV1.5 as it is known to rescue certain expression defects of NaV1.5 in vitro.

Official Title
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Effects of Mexiletine on Colonic Transit in a Patient With a Known SCN5A A997T Mutation

Conditions
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IBS

Intervention / Treatment
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* Drug: Mexiletine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established IBS diagnosis with a known A997T mutation in NaV1.5T Exclusion Criteria: Normal 48-hour baseline transit study Current use of mexiletine Inability to stay in Rochester for 9 days for testing Known allergy to mexiletine Inability to complete daily diary Taking a medication known to affect myotonia, had a coexisting neuromuscular disease, or had another serious medical illness including second- or third-degree heart block, atrial flutter, atrial fibrillation, ventricular arrhythmia, history of cardiac arrhythmia requiring medication, congestive heart failure, symptomatic cardiomyopathy, or symptomatic coronary artery disease Inability to withdraw medications known to interact with mexiletine. Patient is currently not on any of these medications

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mexiletine<br>6-day treatment period during which the medication will be taken orally with an initial dose of: 200 mg every 8 hours for 3 doses on day 3, increasing to 300 mg every 8 hours on days 4 and 5 (6 doses), and increasing further to 400 mg every 8 hours on days 6-8 if no telemetry changes and no dose limiting side effects | Drug: Mexiletine<br>* 6-day treatment period during which the medication will be taken orally with an initial dose of: 200 mg every 8 hours for 3 doses on day 3, increasing to 300 mg every 8 hours on days 4 and 5 (6 doses), and increasing further to 400 mg every 8 hours on days 6-8 if no telemetry changes and no dose limiting side effects<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in the 48 hour Colon Transit | Colon transit will be measured using validated scintigraphy methods conducted in our Clinical Research Unit (CRU).[17, 18] The participant will ingest a Tc-99m labeled sulfur colloid in egg to be used as a stomach marker and ln-111 chloride bound to activated charcoal enclosed in a methacrylate-coated capsule to measure colonic transit. | Baseline to 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IBS