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

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)

Study Overview

• Status: Unknown
• Conditions: Myasthenia Gravis
• Intervention / Treatment: Drug: Pyridostigmine; Drug: Placebo oral capsule

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 Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Midtjylland
    • Aarhus, Midtjylland, Denmark, 8000
      • Recruiting
      • Department of Neurology Aarhus University Hospital
      • Contact: Jan LS Thomsen, MD; Phone Number: +45 7846 6647; Email: jathms@rm.dk
      • Contact: Henning Andersen, MD PhD DMSc; Phone Number: +45 7846 6647; Email: hennande@rm.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; 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; Study dose as per protocol.
Placebo Comparator: Placebo; Same as "Active", however capsules contain placebo.	Drug: Placebo oral capsule; Study dose as per protocol.

What is the study measuring?

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).

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital
• Investigators: Principal Investigator: Jan LS Thomsen, MD, Department of Clinical Medicine, Aarhus University

Publications and helpful links

General Publications

• Burns TM, Conaway M, Sanders DB; MG Composite and MG-QOL15 Study Group. The MG Composite: A valid and reliable outcome measure for myasthenia gravis. Neurology. 2010 May 4;74(18):1434-40. doi: 10.1212/WNL.0b013e3181dc1b1e.
• Barnett C, Katzberg H, Nabavi M, Bril V. The quantitative myasthenia gravis score: comparison with clinical, electrophysiological, and laboratory markers. J Clin Neuromuscul Dis. 2012 Jun;13(4):201-5. doi: 10.1097/CND.0b013e31824619d5.

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2018
• Primary Completion (Anticipated): August 31, 2020
• Study Completion (Anticipated): August 31, 2021

Study Registration Dates

• First Submitted: April 6, 2018
• First Submitted That Met QC Criteria: April 17, 2018
• First Posted (Actual): April 27, 2018

Study Record Updates

• Last Update Posted (Actual): April 27, 2018
• Last Update Submitted That Met QC Criteria: April 17, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Cholinesterase Inhibitors; Pyridostigmine Bromide
• Other Study ID Numbers: Mestinon2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No