Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS)

• Sponsor: Richard Barohn, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01786603
• Collaborator: (none)
• Enrollment: 80
• Locations: 10
• Arms: 2
• Actual Duration (Months): 32.2
• Patients Per Site: 8
• Patients Per Site Per Month: 0.2

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Amyotrophic Lateral Sclerosis (ALS)	Drug: Rasagiline; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of Rasagiline for Treatment of Amyotrophic Lateral Sclerosis
• Actual Study Start Date: Nov 21, 2013
• Actual Primary Completion Date: Jul 27, 2016
• Actual Study Completion Date: Jul 27, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rasagiline Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months.	Drug: Rasagiline; Rasagiline 2mg once a day for 12 months.; Other Names: Azilect
Placebo Comparator: Placebo Inactive ingredient equal to 1mg rasagiline 2mg administered as a single dose once daily for 12 months.	Drug: Placebo; Placebo (looks like study drug but has no active ingredients) once a day for 12 months.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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).

3. 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.

4. 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

5. 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.

6. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Neurological Associates	Phoenix	Arizona	United States	85018
2	University of California - Irvine	Irvine	California	United States	92868
3	California Pacific Medical Center	San Francisco	California	United States	94115
4	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
5	St. Louis University	Saint Louis	Missouri	United States	63104
6	University of Nebraska	Omaha	Nebraska	United States	68198
7	Columbia University	New York	New York	United States	10032
8	Oregon Health and Science University	Portland	Oregon	United States	97239
9	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19107
10	UT Southwestern Medical Center	Dallas	Texas	United States	75390

Sponsors and Collaborators

• Richard Barohn, MD

Investigators

• Principal Investigator: Richard Barohn, MD, University of Kansas Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Richard Barohn, MD, Gertrude and Dewey Zeigler Professor of Neurology and Chair, University of Kansas Medical Center
• ClinicalTrials.gov Identifier: NCT01786603
• Other Study ID Numbers: 12312; R01FD003739
• First Posted: Feb 8, 2013
• Last Update Posted: Jan 27, 2020
• Last Verified: Jan 1, 2020

• Additional relevant MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Rasagiline

Study Results

Participant Flow

Arm/Group Title	Rasagiline	Placebo
Arm/Group Description	Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months. Rasagiline: Rasagiline 2mg once a day for 12 months.	Inactive ingredient equal to 1mg rasagiline 2mg administered as a single dose once daily for 12 months. Placebo: Placebo (looks like study drug but has no active ingredients) once a day for 12 months.
Period Title: Overall Study
STARTED	60	20
COMPLETED	42	8
NOT COMPLETED	18	12

Baseline Characteristics

Arm/Group Title	Rasagiline	Placebo	Total
Arm/Group Description	Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months. Rasagiline: Rasagiline 2mg once a day for 12 months.	Inactive ingredient equal to 1mg rasagiline 2mg administered as a single dose once daily for 12 months. Placebo: Placebo (looks like study drug but has no active ingredients) once a day for 12 months.	Total of all reporting groups
Overall Participants	60	20	80
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.4 (10.2)	57.5 (8.5)	57.95 (9.35)
Sex: Female, Male (Count of Participants)
Female	20 33.3%	7 35%	27 33.8%
Male	40 66.7%	13 65%	53 66.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rasagiline	Placebo
Arm/Group Description	Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months. Rasagiline: Rasagiline 2mg once a day for 12 months.	Inactive ingredient equal to 1mg rasagiline 2mg administered as a single dose once daily for 12 months. Placebo: Placebo (looks like study drug but has no active ingredients) once a day for 12 months.
Measure Participants	60	20
Mean (95% Confidence Interval) [score on a scale]	-1.00	-1.26

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rasagiline	Placebo
Arm/Group Description	Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months. Rasagiline: Rasagiline 2mg once a day for 12 months.	Inactive ingredient equal to 1mg rasagiline 2mg administered as a single dose once daily for 12 months. Placebo: Placebo (looks like study drug but has no active ingredients) once a day for 12 months.
Measure Participants	60	20
Mean (95% Confidence Interval) [Liters]	-2.24	-2.48

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rasagiline	Placebo
Arm/Group Description	Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months. Rasagiline: Rasagiline 2mg once a day for 12 months.	Inactive ingredient equal to 1mg rasagiline 2mg administered as a single dose once daily for 12 months. Placebo: Placebo (looks like study drug but has no active ingredients) once a day for 12 months.
Measure Participants	60	20
Mean (95% Confidence Interval) [Score on a scale]	-0.09	-0.12

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rasagiline	Placebo
Arm/Group Description	Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months. Rasagiline: Rasagiline 2mg once a day for 12 months.	Inactive ingredient equal to 1mg rasagiline 2mg administered as a single dose once daily for 12 months. Placebo: Placebo (looks like study drug but has no active ingredients) once a day for 12 months.
Measure Participants	60	20
Count of Participants [Participants]	28 46.7%	15 75%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rasagiline	Placebo
Arm/Group Description	Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months. Rasagiline: Rasagiline 2mg once a day for 12 months.	Inactive ingredient equal to 1mg rasagiline 2mg administered as a single dose once daily for 12 months. Placebo: Placebo (looks like study drug but has no active ingredients) once a day for 12 months.
Measure Participants	60	20
Count of Participants [Participants]	55 91.7%	19 95%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rasagiline	Placebo
Arm/Group Description	Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months. Rasagiline: Rasagiline 2mg once a day for 12 months.	Inactive ingredient equal to 1mg rasagiline 2mg administered as a single dose once daily for 12 months. Placebo: Placebo (looks like study drug but has no active ingredients) once a day for 12 months.
Measure Participants	60	20
Mean (Standard Deviation) [percentage of change]	0.019 (0.023)	0.02 (0.019)

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rasagiline	Placebo
Arm/Group Description	Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months. Rasagiline: Rasagiline 2mg once a day for 12 months.	Inactive ingredient equal to 1mg rasagiline 2mg administered as a single dose once daily for 12 months. Placebo: Placebo (looks like study drug but has no active ingredients) once a day for 12 months.
Measure Participants	60	20
Mean (Standard Deviation) [pmole/ml]	0.14 (0.73)	1.21 (2.34)

Adverse Events

Arm/Group Title	Rasagiline		Placebo
Arm/Group Description	Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months. Rasagiline: Rasagiline 2mg once a day for 12 months.		Inactive ingredient equal to 1mg rasagiline 2mg administered as a single dose once daily for 12 months. Placebo: Placebo (looks like study drug but has no active ingredients) once a day for 12 months.
All Cause Mortality
	Rasagiline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/60 (8.3%)		1/20 (5%)
Serious Adverse Events
	Rasagiline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Rasagiline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/60 (46.7%)		15/20 (75%)
Blood and lymphatic system disorders
Laboratory Abnormality	6/60 (10%)	6	1/20 (5%)	1
Cardiac disorders
Cardiac	0/60 (0%)	0	1/20 (5%)	1
Ear and labyrinth disorders
Ear and Labyrinth	0/60 (0%)	0	1/20 (5%)	1
Eye disorders
Eye	3/60 (5%)	5	2/20 (10%)	2
Gastrointestinal disorders
Gastrointestinal	22/60 (36.7%)	49	12/20 (60%)	21
General disorders
General Disorders	12/60 (20%)	20	3/20 (15%)	3
Infections and infestations
Infections	11/60 (18.3%)	15	3/20 (15%)	4
Injury, poisoning and procedural complications
Injury, Poisoning, Procedural Complications	11/60 (18.3%)	25	3/20 (15%)	4
Metabolism and nutrition disorders
Metabolism and Nutrition	10/60 (16.7%)	11	3/20 (15%)	3
Musculoskeletal and connective tissue disorders
Musculoskeletal	15/60 (25%)	25	9/20 (45%)	20
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm	1/60 (1.7%)	1	1/20 (5%)	1
Nervous system disorders
Nervous System	16/60 (26.7%)	20	6/20 (30%)	9
Psychiatric disorders
Psychiatric	11/60 (18.3%)	19	6/20 (30%)	11
Renal and urinary disorders
Renal and Urinary	8/60 (13.3%)	8	3/20 (15%)	3
Respiratory, thoracic and mediastinal disorders
Respiratory	15/60 (25%)	25	7/20 (35%)	10
Skin and subcutaneous tissue disorders
Skin	5/60 (8.3%)	6	5/20 (25%)	7
Surgical and medical procedures
Surgical/Medical	2/60 (3.3%)	2	2/20 (10%)	2
Vascular disorders
Vascular	7/60 (11.7%)	10	8/20 (40%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.