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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
Last Update Posted : March 23, 2021
Sponsor:
Information provided by (Responsible Party):
Dwight Koeberl, M.D., Ph.D., Duke University

Brief Summary:
The purpose of this study is to assess the safety and tolerability of clenbuterol (taken by mouth) in subjects with ALS (amyotrophic lateral sclerosis) and to assess the effectiveness of clenbuterol with regard to motor function in subjects with ALS. Subjects will be in this study approximately 24 weeks. The study drug, clenbuterol, is taken twice a day. As part of this study subjects will have the following tests and procedures: medical history, vital signs, physical examination, blood tests, heart and lung function tests, muscle function test, ALSFRS-R (ALS Functional Rating Scale Revised), thyroid function and for women who can become pregnant, pregnancy tests.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: Clenbuterol Phase 2

Detailed Description:
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. In person visits will occur at weeks 0, 4, 12 and 24. Telephone visits will occur at weeks 1, 6, 16 and 20. During these visits several safety and efficacy outcome measures will be performed for research purposes including safety labs, thyroid functions, pregnancy testing, ALSFRS-R, FVC, and muscle strength testing (myometry). The critical test of treatment efficacy will be the comparison of the ALSFRS-R slope during treatment to the estimated pre-treatment slope. All participants will continue to have standard follow up care for their ALS at Duke (for patients followed here) or their local ALS clinic

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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.
Drug: Clenbuterol
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 ERT (Koeberl et al. 2018).




Primary Outcome Measures :
  1. Number of adverse events as measured by patient reporting with dose increase [ Time Frame: Up to 24 weeks ]
    The primary endpoint is safety of clenbuterol at 80 mcg BID. Adverse and serious AEs will be systematically gathered as the dose is increased.


Secondary Outcome Measures :
  1. 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- 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.

  2. Change in motor function measured by forced vital capacity (FVC) [ Time Frame: Baseline, week 4, week 12, and week 24 ]
    FVC is the total amount of air exhaled

  3. Change in motor function as measured by sniff nasal inspiratory [ Time Frame: Baseline, week 4, week 12, and week 24 ]
    Sniff nasal inspiratory pressure measures nasal pressure in an occluded nostril during a maximal sniff performed through the contralateral nostril

  4. Change in motor function as measured by isometric muscle strength [ Time Frame: Baseline, week 4, week 12, and week 24 ]
    This monitors muscle strength deterioration in ALS using the microFET 2 digital hand held dynamometer muscle tester.

  5. Change in motor function as measured by sub-maximum hand grip fatigue [ Time Frame: Baseline, week 4, week 12, and week 24 ]
    Hand strength deterioration is measured by squeezing a dynamometer for a least 5 seconds.



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

Inclusion Criteria:

  • Diagnosis of possible or more definite ALS according to the El Escorial criteria
  • SVC >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

Exclusion Criteria:

  • 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.
  • Pregnancy
  • Clinically relevant EKG abnormality (arrhythmia, cardiomyopathy)
  • Tachycardia (resting heart rate greater than 100 beats per minute)
  • History of seizure disorder
  • Hyperthyroidism
  • Pheochromocytoma
  • Pregnancy
  • 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); MAO 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).


Information from the National Library of Medicine

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


Locations
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United States, North Carolina
Duke University Medical center
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Dwight Koeberl, M.D., Ph.D.
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Responsible Party: Dwight Koeberl, M.D., Ph.D., Professor of Pediatrics, Duke University
ClinicalTrials.gov Identifier: NCT04245709    
Other Study ID Numbers: Pro00103668
First Posted: January 29, 2020    Key Record Dates
Last Update Posted: March 23, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: there is no plan to share IPD with other researchers.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Clenbuterol
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Sympathomimetics