Effect of Salbutamol on Walking Capacity in Ambulatory ALS Patients

NCT05860244 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: APHP190724
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Preclinical and clinical data strongly suggest that administration of salbutamol in ALS patients may improve walking capacity related to motor fatigue by enhancing neuromuscular transmission. Salbutamol may exert a neuroprotective effect and slow down the progression of clinical signs and symptoms. The main objective of the study is to test the efficacy of salbutamol on walking capacity in ALS patients and the secondary objective is to measure the target engagement of salbutamol on the neuromuscular junction (NMJ) at EMG (decrement of repetitive nerve stimulation in three nerves/muscle couples), as well as safety and tolerability. The exploratory objectives are to study the effect of salbutamol on fatigue scales, muscle strength, respiratory function, motor unit count, muscle and spinal MRI parameters and blood biomarkers

Conditions

Walking Capacity; Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic Lateral Sclerosis; Walking capacity; Salbutamol; Ventolin

Outcome Measures

Primary Outcomes (2)

• walking capacity

  6 minutes walking test distance (6MWT)

  Month 6

• walking capacity

  6 minutes walking test distance (6MWT)

  Month 3

Secondary Outcomes (10)

• Target engagement:

  baseline, month 3, month 6

• functional quantitative decline description over time in ALS patients

  baseline, month 3, month 6

• walking scale

  baseline, month 3, month 6

• Fatigue and depression scale

  baseline, month 3, month 6

• Respiratory assessment

  baseline, month 3, month 6

Study Arms (2)

Salbutamol

EXPERIMENTAL

Salbutamol 2mg/5ml syrup : 2mg TID salbutamol for 3 months, then 4 mg TID for 3 months For each investigated dose (6 mg then 12 mg), the treatment will be titrated during a 4 days period: At beginning of the first 3-month period : Month 0 D1: 2mg in the morning; D2-D3: 2 mg in the morning and 2mg in the evening for two days; From D4 and until the end of first 3-month period (until the M3 follow-up visit): 2mg in the morning, at noon and in the evening At beginning of the second 3-month period : Month 3 D1: 4mg in the morning, 2mg at noon, 2 mg in the evening; D2: 4 mg in the morning, 2 mg at noon and 4mg in the evening; J4 and for 3 months (until the M6 follow-up visit) : 4mg in the morning, at noon and in the evening.

Drug: Salbutamol

placebo of salbutamol

PLACEBO COMPARATOR

Placebo syrup : 2mg TID salbutamol for 3 months, then 4 mg TID for 3 months For each investigated dose (6 mg then 12 mg), the treatment will be titrated during a 4 days period: At beginning of the first 3-month period : Month 0 D1: 2mg in the morning; D2-D3: 2 mg in the morning and 2mg in the evening for two days; From D4 and until the end of first 3-month period (until the M3 follow-up visit): 2mg in the morning, at noon and in the evening At beginning of the second 3-month period : Month 3 D1: 4mg in the morning, 2mg at noon, 2 mg in the evening; D2: 4 mg in the morning, 2 mg at noon and 4mg in the evening; J4 and for 3 months (until the M6 follow-up visit) : 4mg in the morning, at noon and in the evening.

Drug: Placebo

Interventions

Salbutamol DRUG

Salbutamol for 6 months

Salbutamol

Placebo DRUG

Placebo Syrup for 6 months

placebo of salbutamol

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who meet the revised El Escorial criteria for probable or definite sporadic ALS
• Adult patients between 18 and 75 years of age
• Patients who are ambulatory and able to perform the 6MWT and quantitative muscle testing at screening (ALSFRS-R-walking = 3)
• Patients able and willing to travel to the site, and, in the investigator's opinion, who are likely to attend visits for at least 6 months
• Patients who signed written informed consent
• Stable dose of riluzole for a minimum of 4 weeks prior to baseline or has not taken it for 4 weeks prior to baseline
• For child-bearing aged women, efficient contraception (cf protocol p32)
• Forced vital capacity (fVC) in a sitting position \> 70 %

You may not qualify if:

• Patients with significant spasticity of the lower limbs interfering with walking capacity (Ashworth scale score \> 2)
• Patients with fronto-temporal dementia associated with ALS
• Patients presenting respiratory insufficiency causing dyspnea during walking
• Patients taking drugs that could interfere with NMJ function (anticholinesterase …) or muscle function (steroids, statins…)
• Patients taking any forbidden drugs (see list in annex)
• Hypersensitivity to salbutamol or to excipients of the drug and placebo
• Known contraindication for the studied drug such as ischemic cardiomyopathy or risk of ischemic cardiomyopathy: history of ischemic heart disease or coronaropathy or/and significant ischemic ECG alterations at screening visit
• Vulnerable persons defined in Articles L1121-5 to L 1121-8-1 and L1122-1-2 of the Code de la Santé Publique\* (\*CSP)
• Patients having any relevant concomitant disease considered at risk of interfering with study procedures in the opinion of the investigator

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Pitié Salpêtrière

Paris, 75013, France

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Albuterol

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Central Study Contacts

Giorgia Querin, MD

CONTACT

01 42 16 58 70; g.querin@institut-myologie.org

Pierre-Francois Pradat, MD

CONTACT

01 42 16 24 71; pierre-francois.pradat@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2023
• First Posted: May 16, 2023
• Study Start: September 1, 2024
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: April 12, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)