Clinical trial NCT01786603: Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS)
Official title: Phase 2 Study of Rasagiline for Treatment of Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis (ALS)
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
First posted: 2013-02-08
Enrollment: 80
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: ALS Functional Rating Scale-Revised (ALSFRS-R)
timeFrame: ALS Functional Rating Scale-Revised (ALSFRS-R) Difference from Baseline to Month 12
Secondary outcomes:
measure: Change in Vital Capacity (VC)
timeFrame: Vital Capacity Change from Baseline to Month 12
measure: Change in Quality of Life
timeFrame: Quality of Life Change from Baseline to Month 12
measure: Number of Participants With Adverse Events
timeFrame: Adverse Events from Baseline to Month 12
measure: Difference in Survival Status Between Study Groups
timeFrame: Survival status at Month 12
measure: Effect of Study Drug on Apoptosis Markers
timeFrame: Apoptosis Marker change from Baseline to Month 12
measure: Effect of Study Drug on Oxidative Stress
timeFrame: Oxidative Stress change from Baseline to Month 12
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Neurological Associates
state: Arizona
city: Irvine
country: United States
facility: University of California - Irvine
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: New York
country: United States
facility: Columbia University
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: University of Kansas Medical Center
name: Richard Barohn, MD
role: PRINCIPAL_INVESTIGATOR
References: