Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS)

Phase 2

Completed

• Conditions: Amyotrophic Lateral Sclerosis (ALS)
• Interventions: Drug: Placebo; Drug: Rasagiline

• Registration Number: NCT01786603
• Lead Sponsor: Richard Barohn, MD

Brief Summary

ALS is a disorder that weakens motor strength and lung function. Rapid loss of motor neurons in the brain and spinal cord of ALS patients causes the symptoms of increasing weakness and loss of muscle function. Motor neurons are responsible for sending signals to muscles in our bodies to trigger movement. While there are drugs to help relieve symptoms of ALS, there is no cure for ALS.

Rasagiline is a drug with possible neuroprotective characteristics. Neuroprotective means that the nervous system may be protected against weakening. It is known that rasagiline has possible neuroprotective characteristics, but the effectiveness of rasagiline for patients with ALS has not been tested. Rasagiline is approved for the treatment of Parkinson's disease.

Rasagiline for treatment of ALS is not approved by the U.S. Food and Drug Administration (FDA) and is investigational. Investigational drugs are studied to find out if they are safe and effective in the treatment of diseases or conditions.

By doing this study, researchers hope to learn if rasagiline is safe and slows disease progression in patients with ALS.

Funding Source - FDA OOPD (FDA Orphan Products Division).

Detailed Description

The study is a phase II, double-blind, placebo-controlled, multicenter study of rasagiline 2mg/day. Subjects will be assigned to either active agent or placebo (3:1) for twelve months. Subjects will undergo outpatient evaluations at screening, baseline, and months 1, 2, 4, 6, 8, 10 and 12 and telephone assessments at months 3, 5, 7 and 9. There will be a close-out phone call 30 days post month 12.

Study Timeline

• Study First Submitted: 2012-11-28
• Study First Submitted QC: 2013-02-05
• Study First Posted: 2013-02-08
• Study Start: 2013-11-21
• Primary Completion: 2016-07-27
• Study Completion: 2016-07-27
• Results First Submitted: 2019-10-15
• Status Verified: 2020-01
• Results First Submitted QC: 2020-01-14
• Last Update Submitted: 2020-01-14
• Results First Posted: 2020-01-27
• Last Update Posted: 2020-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. A clinical diagnosis of laboratory-supported probable, probable, or definite ALS, according to a modified El Escorial criteria, by the study investigator (Appendix IV).
2. 21 to 80 years of age inclusive.
3. VC greater or equal to 75% of predicted at screening and baseline.
4. Onset of weakness within 2 years prior to enrollment.
5. If patients are taking riluzole for ALS, they must be on a stable dose for at least thirty days prior to the baseline visit.
6. Women of childbearing age must be non-lactating and surgically sterile or using an effective method of birth control and have a negative pregnancy test.
7. Willing and able to give signed informed consent that has been approved by the Institutional Review Board (IRB).

Exclusion criteria

1. Requirement for tracheotomy ventilation or non-invasive ventilation for > 23 hours per day.
2. Patients on sympathomimetic agents. This includes pseudoephedrine, phenylephrine, phenylpropanolamine, and ephedrine.
3. Patients on analgesics with serotoninergic properties such as meperidine, tramadol, methadone and propoxyphene, flexeril.
4. Patients on fluoxetine or fluvoxamine.
5. Patients taking amitriptyline > 50 mg/d, trazodone and sertraline > 100 mg/d, citalopram > 20 mg/d or paroxetine > 30 mg/d.
6. Diagnosis of other neurodegenerative diseases (Parkinson disease, Alzheimer disease, etc).
7. Clinically significant history of unstable medical illness (unstable angina, advanced cancer, etc) over the last 30 days.
8. Has a diaphragm pacing device or plan on obtaining a diaphragm pacing device during the course of the study.
9. History of renal disease.
10. History of liver disease.
11. Current pregnancy or lactation.
12. Limited mental capacity such that the patient cannot provide written informed consent or comply with evaluation procedures.
13. History of recent alcohol or drug abuse or noncompliance with treatment or other experimental protocols.
14. Vital Capacity (VC) < 75% of predicted.
15. Receipt of any investigational drug within the past 30 days.
16. Women with the potential to become pregnant who are not practicing effective birth control.
17. Poorly controlled hypertensive subjects or resting systolic blood pressure (SBP) > 160 mmHg and/or diastolic (DBP) > 95 mmHg.
18. Use of BiPAP at screening.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Inactive ingredient equal to 1mg rasagiline 2mg administered as a single dose once daily for 12 months.
Rasagiline	Rasagiline	Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months.

Primary Outcome Measures

Name	Time	Method
ALS Functional Rating Scale-Revised (ALSFRS-R)	ALS Functional Rating Scale-Revised (ALSFRS-R) Difference from Baseline to Month 12	Difference in ALS Functional Rating Scale - Revised (ALSFRS-R) score. The ALSFRS-R is an ordinal rating scale that assesses 12 functional activities. Each activity is scored between 0-4, with a total score ranging from 48 (normal function) to 0 (no function).

Secondary Outcome Measures

Name	Time	Method
Change in Vital Capacity (VC)	Vital Capacity Change from Baseline to Month 12	Determine if decline in vital capacity is slower in participants taking 2 mg rasagiline than controls.
Change in Quality of Life	Quality of Life Change from Baseline to Month 12	Participants completed the single-item ALSQOL (ALS Quality of Life) which asks participants to rank their global quality of life, considering all parts of their lives - physical, emotional, social, spiritual and financial - in the last 7 days and rate on a scale of 0 (very bad) to 10 (excellent).
Difference in Survival Status Between Study Groups	Survival status at Month 12	Determine if there is a difference in survival between participants on rasagiline than patients not on rasagiline
Number of Participants With Adverse Events	Adverse Events from Baseline to Month 12	Determine if participants on rasagiline 2 mg had a different safety profile than patients not on rasagiline. Adverse event information to be collected from date of enrollment until end of study participation.
Effect of Study Drug on Apoptosis Markers	Apoptosis Marker change from Baseline to Month 12	Effect of rasagiline on the apoptosis markers (Annexin V stain) in participants with ALS. Assessed at baseline, month 6, and month 12; change from baseline to month 12 reported. Extra time point was not a pre-specified Primary or Secondary Outcome Measure.
Effect of Study Drug on Oxidative Stress	Oxidative Stress change from Baseline to Month 12	Determine if oxygen radical antioxidant capacity is targeted by rasagiline in participants with ALS. Assessed at baseline, month 6, and month 12; change from baseline to month 12 reported. Extra time point was not a pre-specified Primary or Secondary Outcome Measure.

Trial Locations

Locations (10)

St. Louis University; 🇺🇸 Saint Louis, Missouri, United States

Columbia University; 🇺🇸 New York, New York, United States

California Pacific Medical Center; 🇺🇸 San Francisco, California, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Phoenix Neurological Associates; 🇺🇸 Phoenix, Arizona, United States

University of California - Irvine; 🇺🇸 Irvine, California, United States

University of Nebraska; 🇺🇸 Omaha, Nebraska, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States