Clenbuterol on Motor Function in Individuals With Amyotrophic Lateral Sclerosis

Phase 2

Completed

Conditions: Amyotrophic Lateral Sclerosis

Interventions: Drug: Clenbuterol

Registration Number: NCT04245709

Lead Sponsor: Dwight Koeberl, M.D., Ph.D.

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.

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 (forced vital capacity), 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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 25

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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open label Arm	Clenbuterol	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Serious Adverse Events as Measured by Patient Reporting	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.

Secondary Outcome Measures

Name	Time	Method
FVC Decline, Per-protocol Comparison	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.
Change in Motor Function Measured by ALSFRS-R	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.