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Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS)

Primary Purpose

Amyotrophic Lateral Sclerosis (ALS)

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rasagiline
Placebo
Sponsored by
Richard Barohn, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis (ALS)

Eligibility Criteria

21 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Phoenix Neurological Associates
  • University of California - Irvine
  • California Pacific Medical Center
  • University of Kansas Medical Center
  • St. Louis University
  • University of Nebraska
  • Columbia University
  • Oregon Health and Science University
  • University of Pennsylvania
  • UT Southwestern Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Rasagiline

Placebo

Arm Description

Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months.

Inactive ingredient equal to 1mg rasagiline 2mg administered as a single dose once daily for 12 months.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Change in Vital Capacity (VC)
Determine if decline in vital capacity is slower in participants taking 2 mg rasagiline than controls.
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).
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.
Difference in Survival Status Between Study Groups
Determine if there is a difference in survival between participants on rasagiline than patients not on rasagiline
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.
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.

Full Information

First Posted
November 28, 2012
Last Updated
January 14, 2020
Sponsor
Richard Barohn, MD
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1. Study Identification

Unique Protocol Identification Number
NCT01786603
Brief Title
Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS)
Official Title
Phase 2 Study of Rasagiline for Treatment of Amyotrophic Lateral Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
November 21, 2013 (Actual)
Primary Completion Date
July 27, 2016 (Actual)
Study Completion Date
July 27, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Richard Barohn, MD

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis (ALS)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rasagiline
Arm Type
Experimental
Arm Description
Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Inactive ingredient equal to 1mg rasagiline 2mg administered as a single dose once daily for 12 months.
Intervention Type
Drug
Intervention Name(s)
Rasagiline
Other Intervention Name(s)
Azilect
Intervention Description
Rasagiline 2mg once a day for 12 months.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo (looks like study drug but has no active ingredients) once a day for 12 months.
Primary Outcome Measure Information:
Title
ALS Functional Rating Scale-Revised (ALSFRS-R)
Description
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).
Time Frame
ALS Functional Rating Scale-Revised (ALSFRS-R) Difference from Baseline to Month 12
Secondary Outcome Measure Information:
Title
Change in Vital Capacity (VC)
Description
Determine if decline in vital capacity is slower in participants taking 2 mg rasagiline than controls.
Time Frame
Vital Capacity Change from Baseline to Month 12
Title
Change in Quality of Life
Description
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).
Time Frame
Quality of Life Change from Baseline to Month 12
Title
Number of Participants With Adverse Events
Description
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.
Time Frame
Adverse Events from Baseline to Month 12
Title
Difference in Survival Status Between Study Groups
Description
Determine if there is a difference in survival between participants on rasagiline than patients not on rasagiline
Time Frame
Survival status at Month 12
Title
Effect of Study Drug on Apoptosis Markers
Description
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.
Time Frame
Apoptosis Marker change from Baseline to Month 12
Title
Effect of Study Drug on Oxidative Stress
Description
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.
Time Frame
Oxidative Stress change from Baseline to Month 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: A clinical diagnosis of laboratory-supported probable, probable, or definite ALS, according to a modified El Escorial criteria, by the study investigator (Appendix IV). 21 to 80 years of age inclusive. VC greater or equal to 75% of predicted at screening and baseline. Onset of weakness within 2 years prior to enrollment. If patients are taking riluzole for ALS, they must be on a stable dose for at least thirty days prior to the baseline visit. 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. Willing and able to give signed informed consent that has been approved by the Institutional Review Board (IRB). Exclusion criteria Requirement for tracheotomy ventilation or non-invasive ventilation for > 23 hours per day. Patients on sympathomimetic agents. This includes pseudoephedrine, phenylephrine, phenylpropanolamine, and ephedrine. Patients on analgesics with serotoninergic properties such as meperidine, tramadol, methadone and propoxyphene, flexeril. Patients on fluoxetine or fluvoxamine. Patients taking amitriptyline > 50 mg/d, trazodone and sertraline > 100 mg/d, citalopram > 20 mg/d or paroxetine > 30 mg/d. Diagnosis of other neurodegenerative diseases (Parkinson disease, Alzheimer disease, etc). Clinically significant history of unstable medical illness (unstable angina, advanced cancer, etc) over the last 30 days. Has a diaphragm pacing device or plan on obtaining a diaphragm pacing device during the course of the study. History of renal disease. History of liver disease. Current pregnancy or lactation. Limited mental capacity such that the patient cannot provide written informed consent or comply with evaluation procedures. History of recent alcohol or drug abuse or noncompliance with treatment or other experimental protocols. Vital Capacity (VC) < 75% of predicted. Receipt of any investigational drug within the past 30 days. Women with the potential to become pregnant who are not practicing effective birth control. Poorly controlled hypertensive subjects or resting systolic blood pressure (SBP) > 160 mmHg and/or diastolic (DBP) > 95 mmHg. Use of BiPAP at screening.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Barohn, MD
Organizational Affiliation
University of Kansas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Phoenix Neurological Associates
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85018
Country
United States
Facility Name
University of California - Irvine
City
Irvine
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
California Pacific Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
St. Louis University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
University of Nebraska
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States

12. IPD Sharing Statement

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Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS)

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