Clenbuterol on Motor Function in Individuals With Amyotrophic Lateral Sclerosis

NCT04245709 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: Pro00103668
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Serious Adverse Events as Measured by Patient Reporting

  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.

  Up to 24 weeks

Secondary Outcomes (2)

• Change in Motor Function Measured by ALSFRS-R

  Baseline, week 4, week 12, week 16, week 20, and week 24

• FVC Decline, Per-protocol Comparison

  Baseline, week 4, week 12, and week 24

Study Arms (1)

Open label Arm

EXPERIMENTAL

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

Interventions

Clenbuterol DRUG

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).

Open label Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Dwight Koeberl, M.D., Ph.D.: lead

Study Sites (1)

Duke University Medical center

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Clenbuterol

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Results Point of Contact

• Title: Dwight Koeberl, MD,PhD
• Organization: Duke University

dwight.koeberl@duke.edu

919-681-9919

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: January 26, 2020
• First Posted: January 29, 2020
• Study Start: February 10, 2020
• Primary Completion: March 10, 2021
• Study Completion: March 10, 2021
• Last Updated: September 6, 2022
• Results First Posted: September 6, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)