Effect of Pyridostigmine (Mestinon) on Muscle Strength in Myasthenia Gravis

Study Overview
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Brief Summary
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A randomized, placebo-controlled, double-blinded cross-over study evaluating and quantifying the effect of pyridostigmine on muscle strength and symptoms in Myasthenia Gravis (MG)

Detailed Description
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The study aims to evaluate and quantify the effect of pyridostigmine on symptoms and muscle strength in newly-diagnosed patients and patients on stable medication. Pyridostigmine treatment is initiated in the vast majority of MG patients. No studies have quantified the effect in a randomized trial, and no studies have examined the potential difference in effect in newly diagnosed patients as compared to patients on stable, antimyasthenic medications. The study will investigate the effect in two groups Newly diagnosed, treatment-naive patients. MG patients on stable antimyasthenic medication.

Official Title
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Effect of Pyridostigmine (Mestinon) on Muscle Strength in Myasthenia Gravis

Conditions
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Myasthenia Gravis

Intervention / Treatment
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* Drug: Pyridostigmine
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MG verified by a) anti-body, or b) single-fiber EMG and/or decrement on ENG. Exclusion Criteria: Anti-MuSK Known cardio-pulmonary disease Known neuropathy Known myopathy Known malignant disease Pregnancy or breastfeeding Mechanic ileus, urinary tract obstruction, peritonitis De-novo MG Eligibility Criteria MG diagnosis < 2 months, no prior antimyasthenic medications Chronic MG Eligibility Criteria MG diagnosis > 1 year, and stable pyridostigmine dosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>De-novo: Each capsule contains 60 mg. pyridostigmine. 1 capsule is administered twice within 4 hours. Chronic: Each capsule contains 60 mg. pyridostigmine. Number of administered capsules per dosage depend on the patient's usual dosage. Study drug is administered twice within 4 hours. Patients are examined/rated before 1st dose, 1 hour after 1st dose, 1 hour after 2nd dose (Visit 1). After cross-over (Visit 2), patients will be rated open-label at 1 month (Visit 3) and 3 months (Visit 4). | Drug: Pyridostigmine<br>* Study dose as per protocol.<br>|
| Placebo Comparator: Placebo<br>Same as Active, however capsules contain placebo. | Drug: Placebo oral capsule<br>* Study dose as per protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in QMG | Quantitative Myasthenia Gravis (QMG) scale rate disease severity of myasthenia gravis on 13 items with a total score ranging from 0-39 (higher values representing more severe disease). Total score (0-39), ocular subitems (0-6), bulbar subitems (0-9), extremity/axial subitems (0-21) and respiratory subitem (0-3) will be reported. | At baseline, 1 hour after 1st dose (administered immediately after baseline assessment), 1 hour after 2nd dose (administered 2 hours after 1st dose). Assessed on Day 1 and Day 2 (cross-over), at Follow-up 1 (1 month) and Follow-up 2 (3 months). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle strength as assessed by dynamometry (Biodex System 3). | Peak muscle torque expressed in newton meters based on 3 repeated maximal isometric contractions. Performed on shoulder abduction and knee extension. | At baseline, 1 hour after 1st dose (administered immediately after baseline assessment), 1 hour after 2nd dose (administered 2 hours after 1st dose). Assessed on Day 1 and Day 2 (cross-over), at Follow-up 1 (1 month) and Follow-up 2 (3 months). | 
| Change in muscle fatigue as assessed by dynamometry (Biodex System 3). | Decrement in peak muscle torque expressed in newton meters per contraction during up to 50 repetitive maximal isokinetic contractions. Performed on shoulder abduction and knee extension. | At baseline, 1 hour after 1st dose (administered immediately after baseline assessment), 1 hour after 2nd dose (administered 2 hours after 1st dose). Assessed on Day 1 and Day 2 (cross-over), at Follow-up 1 (1 month) and Follow-up 2 (3 months). | 
| Change in MG Composite Score | The Myasthenia Gravis Composite (MG composite) scale rate disease severity of myasthenia gravis on 10 items with a score ranging from 0-50 (higher values representing more severe disease). | At baseline, 1 hour after 1st dose (administered immediately after baseline assessment), 1 hour after 2nd dose (administered 2 hours after 1st dose). Assessed on Day 1 and Day 2 (cross-over), at Follow-up 1 (1 month) and Follow-up 2 (3 months). |