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

• Sponsor: University of Aarhus (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT03510546
• Collaborator: Aarhus University Hospital (Other)
• Enrollment: 44
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 40.7
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Myasthenia Gravis	Drug: Pyridostigmine; Drug: Placebo oral capsule	Phase 4

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Pyridostigmine (Mestinon) on Muscle Strength in Myasthenia Gravis
• Actual Study Start Date: Apr 9, 2018
• Anticipated Primary Completion Date: Aug 31, 2020
• Anticipated Study Completion Date: Aug 31, 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Neurology Aarhus University Hospital	Aarhus	Midtjylland	Denmark	8000

Sponsors and Collaborators

• University of Aarhus
• Aarhus University Hospital

Investigators

• Principal Investigator: Jan LS Thomsen, MD, Department of Clinical Medicine, Aarhus University

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.

• Responsible Party: Jan Lykke Scheel Thomsen, MD, PhD Fellow, University of Aarhus
• ClinicalTrials.gov Identifier: NCT03510546
• Other Study ID Numbers: Mestinon2018
• First Posted: Apr 27, 2018
• Last Update Posted: Apr 27, 2018
• Last Verified: Apr 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Myasthenia Gravis; Muscle Weakness; Pyridostigmine Bromide

Study Results

No Results Posted as of Apr 27, 2018