Clenbuterol on Motor Function in Individuals With Amyotrophic Lateral Sclerosis
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Intervention: Clenbuterol
Intervention description: 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).
Intervention MeSH terms: Clenbuterol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

        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); 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).