Trial of Safety and Efficacy of Rasagiline in Patients With Amyotrophic Lateral Sclerosis (ALS)

A Multi-Center Controlled Screening Trial of Safety and Efficacy of Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS)

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. 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 and it is approved for use for patients with another disorder, the effectiveness of rasagiline for patients with ALS has not been tested.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis (ALS)
• Intervention / Treatment: Drug: rasagiline

Detailed Description

The specific aim of this screen study is to determine whether rasagiline is safe in this patient population and if the drug has the potential to slow ALS disease progression

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • McGill University
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Phoenix Neurological Institute
  • California
    • San Francisco, California, United States, 94118
      • California Pacific Medical Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • University of Minnesota
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • University of Tennessee
  • Texas
    • Houston, Texas, United States, 77030
      • The Methodist Hospital System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 3 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 propoxyphen, flexeril.
4. Patients on fluoxetine or fluvoxamine.
5. Patients taking amitriptyline > 50 mg/d, trazodone and sertraline > 100 mg/d, citalogram > 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. History of renal disease.
9. History of liver disease.
10. Current pregnancy or lactation.
11. Limited mental capacity such that the patient cannot provide written informed consent or comply with evaluation procedures.
12. History of recent alcohol or drug abuse or noncompliance with treatment or other experimental protocols.
13. VC < 75% of predicted.
14. Receipt of any investigational drug within the past 30 days.
15. Women with the potential to become pregnant who are not practicing effective birth control.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rasagiline; Treated for 12 months with rasagiline 2mg orally, once daily.	Drug: rasagiline; rasagiline 2 mg daily for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R)	The primary outcome measure is the difference in the rate of decline in function, as detected by the ALS Functional Rating Scale - Revised (ALSFRS-R) in patients taking rasagiline compared to a database of patients from randomized clinical trials conducted during 1997-2007. Minimum score is 0 (no function) to Maximum score is 48 (normal function)	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Time to Treatment Failure	This group is defined as death, endotracheal intubation, tracheostomy-assisted ventilation or use of noninvasive ventilation >= 23 hours/day for 14 days or more.	up to 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in JC-1 Mitochondrial Biomarkers	The 12 month change in mitochondrial biomarkerJC-1 red/green fluorescence ratio. We measured at baseline, 6 months and 12 months.	Baseline, 6 months, 12 months
Change in Mitotracker Mitochondrial Biomarkers	The 12 month change in mitochondrial biomarkerMitotracker. We measured at baseline, 6 months and 12 months.	Baseline, 6 months, 12 months
Change in Percent Annexin V Mitochondrial Biomarkers	The 12 month change in mitochondrial biomarker Annexin V %. We measured at baseline, 6 months and 12 months.	Baseline, 6 months, 12 months
Change in BCL2/BAX Mitochondrial Biomarkers	The 12 month change in mitochondrial biomarker BCL2/BAX. We measured at baseline, 6 months and 12 months.	Baseline, 6 months, 12 months
Change in ORAC Mitochondrial Biomarkers	The 12 month change in mitochondrial biomarker Oxygen Radical Antioxidant Capacity. We measured at baseline, 6 months and 12 months.	Baseline, 6 months, 12 months

Collaborators and Investigators

• Sponsor: Yunxia Wang, MD
• Collaborators: Western ALS Study Group
• Investigators: Principal Investigator: Yunxia Wang, MD, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: October 22, 2010
• First Submitted That Met QC Criteria: October 29, 2010
• First Posted (Estimate): November 2, 2010

Study Record Updates

• Last Update Posted (Actual): May 18, 2018
• Last Update Submitted That Met QC Criteria: April 17, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Monoamine Oxidase Inhibitors; Rasagiline
• Other Study ID Numbers: 11922