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

Phase 4

• Conditions: Myasthenia Gravis
• Interventions: Drug: Pyridostigmine; Drug: Placebo oral capsule

• Registration Number: NCT03510546
• Lead Sponsor: University of Aarhus

Brief Summary

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

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

1. Newly diagnosed, treatment-naive patients.

2. MG patients on stable antimyasthenic medication.

Study Timeline

• Status Verified: 2018-04
• Study First Submitted: 2018-04-06
• Study Start: 2018-04-09
• Study First Submitted QC: 2018-04-17
• Last Update Submitted: 2018-04-17
• Study First Posted: 2018-04-27
• Last Update Posted: 2018-04-27
• Primary Completion: 2020-08-31
• Study Completion: 2021-08-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 44

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Active	Pyridostigmine	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).
Placebo	Placebo oral capsule	Same as "Active", however capsules contain placebo.

Primary Outcome Measures

Name	Time	Method
Change in QMG	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).	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.

Secondary Outcome Measures

Name	Time	Method
Change in muscle strength as assessed by dynamometry (Biodex System 3).	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).	Peak muscle torque expressed in newton meters based on 3 repeated maximal isometric contractions. Performed on shoulder abduction and knee extension.
Change in MG Composite Score	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).	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).
Change in muscle fatigue as assessed by dynamometry (Biodex System 3).	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).	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.

Trial Locations

Locations (1)

Department of Neurology Aarhus University Hospital; 🇩🇰 Aarhus, Midtjylland, Denmark