Beta-agonist Efficacy and Tolerability as Adjuvant Therapy in Myasthenia Gravis

Myasthenia Gravis Clinical Trial

— BETA-MG  

Official title:

Beta-agonist Efficacy and Tolerability as Adjuvant Therapy in Myasthenia Gravis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03914638
• Other study ID #: BETA-MG-01
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: April 1, 2019
• Est. completion date: October 31, 2021

Study information

• Verified date: April 2020
• Source: University of Aarhus
• Contact: Jan LS Thomsen, MD
• Phone: 78450000
• Email: jathms[@]rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 31, 2021
• Est. primary completion date: October 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Muscle Weakness
• Myasthenia Gravis

Intervention

Drug:
• Salbutamol 4Mg Tablet
Salbutamol 4 mg, three times daily
• Placebo oral capsule
Placebo, three times daily

Locations

Country	Name	City	State
Denmark	Department of Neurology, Aalborg University Hospital	Aalborg
Denmark	Neurology, Aarhus University Hospital	Aarhus

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myasthenia Gravis Quality of Life 15-items (MG-QOL15)	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).	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)
Primary	Treatment Tolerability	Tolerability assessed by rate of adverse events and drug discontinuation in both treatment periods.	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)
Secondary	Myasthenia Gravis Activity of Daily Living (MG-ADL)	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).	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)
Secondary	Neuro QOL	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).	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)
Secondary	Quantitative Myasthenia Gravis (QMG)	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).	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)
Secondary	Myasthenia Gravis Composite (MG-Composite)	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).	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)