Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis (ALS) Clinical Trial

Official title:

Phase 2 Study of Rasagiline for Treatment of Amyotrophic Lateral Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01786603
• Other study ID #: 12312
• Secondary ID: R01FD003739
• Status: Completed
• Phase: Phase 2
• Start date: November 21, 2013
• Est. completion date: July 27, 2016

Study information

• Verified date: January 2020
• Source: University of Kansas Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: July 27, 2016
• Est. primary completion date: July 27, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Amyotrophic Lateral Sclerosis (ALS)
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Rasagiline
Rasagiline 2mg once a day for 12 months.
• Placebo
Placebo (looks like study drug but has no active ingredients) once a day for 12 months.

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center	Dallas	Texas
United States	University of California - Irvine	Irvine	California
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Columbia University	New York	New York
United States	University of Nebraska	Omaha	Nebraska
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Phoenix Neurological Associates	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	St. Louis University	Saint Louis	Missouri
United States	California Pacific Medical Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Richard Barohn, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ALS Functional Rating Scale-Revised (ALSFRS-R)	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).	ALS Functional Rating Scale-Revised (ALSFRS-R) Difference from Baseline to Month 12
Secondary	Change in Vital Capacity (VC)	Determine if decline in vital capacity is slower in participants taking 2 mg rasagiline than controls.	Vital Capacity Change from Baseline to Month 12
Secondary	Change in Quality of Life	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).	Quality of Life Change from Baseline to Month 12
Secondary	Number of Participants With Adverse Events	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.	Adverse Events from Baseline to Month 12
Secondary	Difference in Survival Status Between Study Groups	Determine if there is a difference in survival between participants on rasagiline than patients not on rasagiline	Survival status at Month 12
Secondary	Effect of Study Drug on Apoptosis Markers	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.	Apoptosis Marker change from Baseline to Month 12
Secondary	Effect of Study Drug on Oxidative Stress	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.	Oxidative Stress change from Baseline to Month 12