Walking CapacityPhase 2WALKALSNCT05860244
Effect of Salbutamol on Walking Capacity in Ambulatory ALS Patients
A Phase 2 study testing Salbutamol in people with Walking Capacity and Amyotrophic Lateral Sclerosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Walking Capacity, Amyotrophic Lateral Sclerosis
- What is being tested?
- Salbutamol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2024to Jul 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 %
Who cannot join
- 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
Show all 11Show fewer
- 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
- Any clinically significant alterations in the following biological parameters glycemia, kalemia, creatinemia and hematology in the month prior to inclusion according to local laboratory threshold (cf protocol page 33)
- Vulnerable persons defined in Articles L1121-5 to L 1121-8-1 and L1122-1-2 of the Code de la Santé Publique* (*CSP)
- Participation in another interventional trial up to 3 months before inclusion
- Patients having any relevant concomitant disease considered at risk of interfering with study procedures in the opinion of the investigator
Trial locations and contacts
1 site in 1 country.
France1 site
Hôpital Pitié Salpêtrière
Paris, 75013
Giorgia Querin, MD, 01 42 16 58 70 ext. +33, g.querin@institut-myologie.org
About this study
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
Read the detailed description
Based on a strong preclinical and clinical rationale the main hypothesis is that the administration of salbutamol in ALS patients may improve the walking capacity related to motor fatigue by enhancing the neuromuscular transmission. Salbutamol may also exert a neuroprotective effect and slow down the progression of clinical signs and symptoms.
To test these hypotheses, the investigator team will implement a monocentric, randomized, controlled, pilot study to evaluate the effect of salbutamol on walking capacity in ambulatory ALS patients with a total duration of 24 months and a treatment period of 6 months for each patient. The project Team will use as secondary and exploratory endpoints target engagement and efficacy up-to date biomarkers such as quantitative muscle strength evaluation, functional neuromuscular evaluation and spinal and muscle MRI. Tolerability and safety will also be studied. Salbutamol has been used for a long time and is usually well tolerated. The objective of the study is to evidence a signal of efficacy paving the way for a confirmatory phase 3 trial.
In parallel to this, the use of muscle and spinal MRI as well as of quantitative muscle strength evaluation as exploratory endpoints will pave the way to their development as biomarkers of disease progression in ALS. Thanks to the data collected in this study, the team will give proof of their accuracy, with a view to ameliorate the prognostication and monitoring of disease progression and survival, as well as to improve the understanding of the interaction between muscular and central degeneration. A further aim of this study will be to provide a proof of concept that spinal and muscle MRI can constitute a biomarker of the efficacy of investigational drugs targeting muscles.
- Conditions
- Walking Capacity, Amyotrophic Lateral Sclerosis
- Being tested
- Salbutamol, Placebo
- Keywords
- Amyotrophic Lateral Sclerosis, Walking capacity, Salbutamol, Ventolin
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalbutamolDrug
Salbutamol for 6 months
PlaceboDrug
Placebo Syrup for 6 months
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
walking capacity
6 minutes walking test distance (6MWT)
Measured: Month 6
walking capacity
6 minutes walking test distance (6MWT)
Measured: Month 3
Secondary outcomes (10)
Target engagement:
percentage of change of the decrement at electromyography after repetitive nerve stimulation.
Measured: baseline, month 3, month 6
functional quantitative decline description over time in ALS patients
Revised ALS Functional Rating Scale-r (ALSFRS-r) composed by 12 questions scoring from 0 to 4 with a maximal score of 48
Measured: baseline, month 3, month 6
walking scale
Twelve items Multiple Sclerosis (MS) Walking Scale (12-MSWS) ( score: 5 to 60 ( severe difficulty)) . Walking improvement on the MSWS-12 is indicated by negative change scores.
Measured: baseline, month 3, month 6
Fatigue and depression scale
Fatigue Severity Scale (FSS) is a 9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle in patients with a variety of disorders. ( score : 9 (no fatigue ) to 63 (extreme fatigue)
Measured: baseline, month 3, month 6
Respiratory assessment
Forced Vital Capacity (FVC): the maximum amount of air that a person can exhale as hard and as long as possible from the lungs after a maximum inspiration and Forced Expiratory Volume in the first second of exhalation (FEV1) : FEV1 is the most frequently used index for assessing airway obstruction, bronchoconstriction or bronchodilation
Measured: baseline, month 3, month 6
Thigh muscle volume
bioelectrical impedance analysis (BIA)
Measured: baseline, month 3, month 6
Muscle volume
Muscle MRI in cm3
Measured: baseline, month 3, month 6
Biomarkers of muscle damage
CPK, LDH and creatinine serum levels
Measured: baseline, month 3, month 6
Quality of life scale
The Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) ( score: 0 to 160 bad quality of life)
Measured: baseline, month 6
Motor unit number
Motor unit count (MUNIX method)
Measured: baseline, month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2023
- Study startSep 2024 (estimated)
- Primary completionJul 2025 (estimated)
- Study completionJul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Walking CapacityStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05860244
- Sponsor's protocol ID
- APHP190724
- Acronym
- WALKALS
- Status last verified
- Apr 2024
- First submitted
- 24 Apr 2023
- Last updated
- 12 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Salbutamol on Walking Capacity in Ambulatory ALS Patients
- ClinicalTrials.gov ID
- NCT05860244
- Acronym / sponsor ID
- WALKALS / APHP190724
- Conditions
- Walking Capacity, Amyotrophic Lateral Sclerosis
- Keywords
- Amyotrophic Lateral Sclerosis, Walking capacity, Salbutamol, Ventolin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Sep 2024 (estimated)
- Primary completion
- Jul 2025 (estimated)
- Study completion
- Jul 2025 (estimated)
- First posted
- 16 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Based on a strong preclinical and clinical rationale the main hypothesis is that the administration of salbutamol in ALS patients may improve the walking capacity related to motor fatigue by enhancing the neuromuscular transmission. Salbutamol may also exert a neuroprotective effect and slow down the progression of clinical signs and symptoms.
To test these hypotheses, the investigator team will implement a monocentric, randomized, controlled, pilot study to evaluate the effect of salbutamol on walking capacity in ambulatory ALS patients with a total duration of 24 months and a treatment period of 6 months for each patient. The project Team will use as secondary and exploratory endpoints target engagement and efficacy up-to date biomarkers such as quantitative muscle strength evaluation, functional neuromuscular evaluation and spinal and muscle MRI. Tolerability and safety will also be studied. Salbutamol has been used for a long time and is usually well tolerated. The objective of the study is to evidence a signal of efficacy paving the way for a confirmatory phase 3 trial.
In parallel to this, the use of muscle and spinal MRI as well as of quantitative muscle strength evaluation as exploratory endpoints will pave the way to their development as biomarkers of disease progression in ALS. Thanks to the data collected in this study, the team will give proof of their accuracy, with a view to ameliorate the prognostication and monitoring of disease progression and survival, as well as to improve the understanding of the interaction between muscular and central degeneration. A further aim of this study will be to provide a proof of concept that spinal and muscle MRI can constitute a biomarker of the efficacy of investigational drugs targeting muscles.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Salbutamol | Experimental | Drug: SalbutamolSalbutamol 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. |
| placebo of salbutamol | Placebo comparator | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SalbutamolSalbutamol for 6 months | Drug | Salbutamol |
| PlaceboPlacebo Syrup for 6 months | Drug | placebo of salbutamol |
Primary outcome
walking capacity
Time frame: Month 6
6 minutes walking test distance (6MWT)
walking capacity
Time frame: Month 3
6 minutes walking test distance (6MWT)
10 secondary outcomes
Target engagement:
Time frame: baseline, month 3, month 6
functional quantitative decline description over time in ALS patients
Time frame: baseline, month 3, month 6
walking scale
Time frame: baseline, month 3, month 6
Fatigue and depression scale
Time frame: baseline, month 3, month 6
Respiratory assessment
Time frame: baseline, month 3, month 6
Thigh muscle volume
Time frame: baseline, month 3, month 6
Muscle volume
Time frame: baseline, month 3, month 6
Biomarkers of muscle damage
Time frame: baseline, month 3, month 6
Quality of life scale
Time frame: baseline, month 6
Motor unit number
Time frame: baseline, month 6
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Salbutamol in people with Walking Capacity and Amyotrophic Lateral Sclerosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Giorgia Querin, MD (01 42 16 58 70 ext. +33, g.querin@institut-myologie.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
walking capacity (time frame: Month 6). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2024.