Clenbuterol on Motor Function in Individuals With Amyotrophic Lateral Sclerosis
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|ClinicalTrials.gov Identifier: NCT04245709|
Recruitment Status : Completed
First Posted : January 29, 2020
Results First Posted : September 6, 2022
Last Update Posted : September 6, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Amyotrophic Lateral Sclerosis||Drug: Clenbuterol||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Clinical Investigation of the Safety and Efficacy of Clenbuterol on Motor Function in Individuals With Amyotrophic Lateral Sclerosis|
|Actual Study Start Date :||February 10, 2020|
|Actual Primary Completion Date :||March 10, 2021|
|Actual Study Completion Date :||March 10, 2021|
Experimental: Open label Arm
This is an open label pilot trial in which 25 people with ALS will take clenbuterol orally at 40-80 micrograms twice daily for 24 weeks.
The intervention is treatment with oral clenbuterol at 40-80 micrograms twice daily for 24 weeks. Dosage will initially be 40 mcg daily for one week, then 40 mcg BID per oral daily for the next 5 weeks. If the 40 mcg BID per oral is well tolerated in the opinion of Dr. Bedlack, the dose will be increased to 80 mcg each morning/40 mcg each evening for one week, followed by 80 mcg BID per oral for the remainder of the study. The selected target dose (80 mcg BID) is based upon the experience with the long-term administration of clenbuterol, specifically the beneficial muscle effects in a Phase I/II clinical trial that enrolled patients with late-onset Pompe disease who were previously treated with enzyme replacement therapy (Koeberl et al. 2018).
- Number of Participants With Serious Adverse Events as Measured by Patient Reporting [ Time Frame: Up to 24 weeks ]The primary endpoint is safety of clenbuterol at 80 mcg BID. Adverse events and serious adverse events will be systematically gathered as the dose is increased.
- Change in Motor Function Measured by ALSFRS-R [ Time Frame: Baseline, week 4, week 12, week 16, week 20, and week 24 ]The ALS Functional Rating Scale (ALSFRS-R) - 12 questions rated on a five-point scale, where 0= can't do, to 5= normal ability. It is utilized for monitoring the progression of disability in patients with ALS. The critical test for efficacy was comparison of the mean slope of the ALSFRS-R during treatment compared to pre-treatment. Pre-treatment slope for each participant was estimated as follows: (48-enrollment ALSFRS-R)/months since symptom onset. A statistically significant treatment effect was determined by a two-tailed, t-test, with a critical p value < .05. Other analyses included a repeated measures ANOVA design (between and within subjects) of ALSFRS-R slopes before and during treatment.
- FVC Decline, Per-protocol Comparison [ Time Frame: Baseline, week 4, week 12, and week 24 ]Comparison of the mean slope of percent predicted FVC during treatment versus pre-treatment. Pre-treatment slope for each participant was estimated as follows: (100%-enrollment percent predicted FVC)/months since symptom onset.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Diagnosis of possible or more definite ALS according to the El Escorial criteria
- FVC >50% of predicted for age, height and gender.
- At least four of 12 ALSFRS-R questions scored as 2 or 3 at screening.
- Diminished but measurable grip strength (1) in at least one hand (females:10-50 pounds; males, 10-70 pounds).
- Taking riluzole at a stable dose or not taking riluzole at screening.
- On Radicava at a stable dose for at least 30d or not taking this
- Life expectancy at least 6 months
- Able to swallow tablets without crushing.
- Age: 18+ years at enrollment.
- Subjects are capable of giving written consent.
- If sexually active, must agree to use contraceptive or abstinence for duration of treatment
- Females of child bearing age must have negative pregnancy test at screening
- Concurrent illness or laboratory abnormalities that could confound the measurement of ALS progression or interfere with the ability to complete the study.
- Taking any investigational study drug within 30 days of screening or five half-lives of the prior agent.
- No previous exposure to clenbuterol.
- Clinically relevant EKG abnormality (arrhythmia, cardiomyopathy)
- Tachycardia (resting heart rate greater than 100 beats per minute)
- History of seizure disorder
- Have any other co-morbid conditions that in the opinion of the study investigator, places the participant at increased risk of complications, interferes with study participation or compliance, or confounds study objectives
- History of hypersensitivity to 2-agonist drugs such as albuterol, levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline, salmeterol (Serevent).
- The use of the following concomitant meds is prohibited during the study:
diuretics (furosemide, Lasix), digoxin (digitalis, Lanoxin);blockers such as atenolol (Tenormin), metoprolol (Lopressor), and propranolol (Inderal); tricyclic antidepressants such as amitriptyline (Elavil, Etrafon), doxepin (Sinequan), imipramine (Janimine, Tofranil), and nortriptyline (Pamelor); monoamine oxidase inhibitors such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate); or other bronchodilators such as albuterol (Ventolin), levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline (Brethine, Bricanyl), salmeterol (Serevent), isoetherine (Bronkometer), metaproterenol (Alupent, Metaprel), or isoproterenol (Isuprel Mistometer).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04245709
|United States, North Carolina|
|Duke University Medical center|
|Durham, North Carolina, United States, 27705|
Documents provided by Dwight Koeberl, M.D., Ph.D., Duke University:
|Responsible Party:||Dwight Koeberl, M.D., Ph.D., Professor of Pediatrics, Duke University|
|Other Study ID Numbers:||
|First Posted:||January 29, 2020 Key Record Dates|
|Results First Posted:||September 6, 2022|
|Last Update Posted:||September 6, 2022|
|Last Verified:||August 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Plan Description:||there is no plan to share individual participant data (IPD) with other researchers.|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Peripheral Nervous System Agents
Respiratory System Agents