Beta-agonist Efficacy and Tolerability as Adjuvant Therapy in Myasthenia Gravis (BETA-MG)

• ClinicalTrials.gov Identifier: NCT03914638
• Recruitment Status: Recruiting
• First Posted: April 16, 2019
• Last Update Posted: April 6, 2020
• Sponsor: University of Aarhus
• Information provided by (Responsible Party): Jan Lykke Scheel Thomsen, University of Aarhus

Study Description

Brief Summary:

This study examines the effect of adjuvant therapy with the oral beta-agonist Salbutamol in patients with generalized myasthenia gravis on stable standard of care having residual symptoms.

Condition or disease	Intervention/treatment	Phase
Myasthenia Gravis	Drug: Salbutamol 4Mg Tablet; Drug: Placebo oral capsule	Phase 2; Phase 3

Detailed Description:

Myasthenia Gravis (MG) causes various degrees of increased muscular fatigue and ocular, bulbar, respiratory and extremity symptoms.

Residual symptoms often remain despite treatment with acetylcholinesterase inhibitors and immunosuppressive agents. Escalation of immunosuppressive treatment may provide additional benefit but is associated with potentially severe side effects, and high economic costs.

Treatment with beta-agonists has been investigated in animal models of MG, and in small, randomized pilot studies of generalized MG. Adjuvant therapy with oral beta-agonists in MG may be safe and cheap and may improve symptoms.

The trial will examine the tolerability and efficacy of adjuvant therapy with the oral beta-agonist Salbutamol in patients with generalized myasthenia gravis on stable standard of care having residual symptoms.

Present study is an investigator-initiated, randomized, placebo-controlled, rater and subject-blinded crossover study.

Study consists of Screening Period (4 weeks), Treatment Period 1 (8 weeks), Washout Period (4 weeks), Treatment Period 2 (8 weeks).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Beta-agonist Efficacy and Tolerability as Adjuvant Therapy in Myasthenia Gravis
• Actual Study Start Date: April 1, 2019
• Estimated Primary Completion Date: October 31, 2021
• Estimated Study Completion Date: October 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Active; Active intervention arm. Treatment for 8 weeks per treatment period.	Drug: Salbutamol 4Mg Tablet; Salbutamol 4 mg, three times daily
Placebo Comparator: Placebo; Placebo arm. Treatment for 8 weeks per treatment period.	Drug: Placebo oral capsule; Placebo, three times daily

Outcome Measures

Primary Outcome Measures :

1. Myasthenia Gravis Quality of Life 15-items (MG-QOL15) [ Time Frame: 8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2) ]
   Validated patient reported outcome-questionnaire consisting of 15 items and their impact on quality of life. Results are reported as change from baseline to 8 weeks of treatment in both treatment periods (Visit 4 compared to Visit 2, and Visit 7 compared to Visit 5).
2. Treatment Tolerability [ Time Frame: 8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2) ]
   Tolerability assessed by rate of adverse events and drug discontinuation in both treatment periods.

Secondary Outcome Measures :

1. Myasthenia Gravis Activity of Daily Living (MG-ADL) [ Time Frame: 8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2) ]
   Validated patient-reported outcome scale consisting of 8 disease-related items and their impact on activity of daily living. Results are reported as change from baseline to 8 weeks of treatment in both treatment periods (Visit 4 compared to Visit 2, and Visit 7 compared to Visit 5).
2. Neuro QOL [ Time Frame: 8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2) ]
   Patient reported fatigue-questionnaire used to rate fatigue and impact on quality of life. Results are reported as change from baseline to 8 weeks of treatment in both treatment periods (Visit 4 compared to Visit 2, and Visit 7 compared to Visit 5).
3. Quantitative Myasthenia Gravis (QMG) [ Time Frame: 8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2) ]
   Validated rating scale consisting of 13 items measuring muscle function and endurance. Results are reported as change from baseline to 8 weeks of treatment in both treatment periods (Visit 4 compared to Visit 2, and Visit 7 compared to Visit 5).
4. Myasthenia Gravis Composite (MG-Composite) [ Time Frame: 8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2) ]
   Validated scale consisting of 10 items with different weighting assessing severity of symptoms in MG. Results are reported as change from baseline to 8 weeks of treatment in both treatment periods (Visit 4 compared to Visit 2, and Visit 7 compared to Visit 5).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Generalized myasthenia gravis (MGFA IIa-IVb) at screening, verified by ≥ 1 of the following: 1) AchR-antibodies in medical history, 2) Abnormal decrement on repetitive nerve stimulation in medical history
• Disease duration of ≥ 1 year
• Stable dose of antimyasthenic medications at screening
• Residual symptoms with a MG-QOL15 score of ≥ 10
• Age ≥ 18 years
• Ability to understand the requirements of the trial and provide written, informed consent

Exclusion Criteria:

• Evidence of malignancy ≤ 3 years prior to screening, unless deemed completely cured
• Thymectomy ≤ 6 months prior to screening
• Impending MG crisis or respiratory insufficiency
• Worsening of MG symptoms due to other diseases or medications (e.g. infection, beta-blockers, aminoglycosides, etc.)
• Other factor(s) or medical condition(s) that may explain residual symptoms
• Pregnancy or breast-feeding
• Treatment with beta-agonists
• Uncontrolled diabetes
• Ischemic Heart Disease, Cardiac Arrhythmia or Heart Failure (including hypertrophic cardiomyopathy)
• Uncontrolled Hypertension (≥ 160/110)
• Known hypersensitivity to any of the study drug components
• Treatment with tricyclic antidepressants, monoamineoxidase inhibitors, digoxine, or methylxanthines.

Contacts and Locations

Contacts

Contact: Jan LS Thomsen, MD; 78450000 ext 0045; jathms@rm.dk

Locations

Denmark

Department of Neurology, Aalborg University Hospital; Recruiting

Aalborg, Denmark, 9000

Contact: Izabella Obál, PhD

Neurology, Aarhus University Hospital; Recruiting

Aarhus, Denmark, 8200

Contact: Jan Thomsen

Sponsors and Collaborators

University of Aarhus

Investigators

• Study Director: Jan LS Thomsen, MD; Department of Clinical Medicine, Aarhus University

More Information

• Responsible Party: Jan Lykke Scheel Thomsen, MD, PhD Fellow, University of Aarhus
• ClinicalTrials.gov Identifier: NCT03914638
• Other Study ID Numbers: BETA-MG-01
• First Posted: April 16, 2019
• Last Update Posted: April 6, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• 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:

Muscle Weakness; Myasthenia Gravis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Autoimmune Diseases of the Nervous System; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Albuterol; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Tocolytic Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action