Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Richard Barohn, MD, University of Kansas Medical Center Research Institute
ClinicalTrials.gov Identifier:
NCT01786603
First received: November 28, 2012
Last updated: May 1, 2016
Last verified: May 2016
  Purpose

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.


Condition Intervention Phase
Amyotrophic Lateral Sclerosis (ALS)
Drug: Rasagiline
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Phase 2 Study of Rasagiline for Treatment of Amyotrophic Lateral Sclerosis IND# 104,360

Resource links provided by NLM:


Further study details as provided by University of Kansas Medical Center:

Primary Outcome Measures:
  • Change in the ALS Functional Rating Scale-Revised (ALSFRS-R) [ Time Frame: Change from Baseline in ALSFRS-R at 12 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: Change from Baseline in VC at 12 months ] [ Designated as safety issue: No ]
    Determine if decline in vital capacity is slower in patients taking 2 mg rasagiline than controls.

  • Change in quality of life [ Time Frame: Change from Baseline in Quality of Life at 12 months ] [ Designated as safety issue: No ]
    determine if quality of life improves in patients taking 2 mg rasagiline

  • Number of participants with adverse events [ Time Frame: up to 12 months ] [ Designated as safety issue: Yes ]
    Determine if patients 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 [ Time Frame: Change from Baseline in survival status at 12 months ] [ Designated as safety issue: No ]
    Determine if there is a difference in survival between patients on rasagiline than patients not on rasagiline

  • Bcl2Bax expression ratio in RNA samples [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
    Test to determine if rasagiline targets the Bcl2/Bax expression ration in RNA.

  • Biomarker Assays of Mitochondrial Function [ Time Frame: Change from Baseline in Biomarker Assays at 12 months ] [ Designated as safety issue: No ]
    Determine if rasagiline targets mitochondrial membrane potentials. Effect determined by comparing mean slopes of the study groups.

  • Effect of study drug on apoptosis markers [ Time Frame: Change from Baseline in Apoptosis Markers at 12 months ] [ Designated as safety issue: No ]
    Effect of rasagiline on the apoptosis markers in patients with ALS

  • Effect of study drug on oxidative stress [ Time Frame: Change from Baseline in Oxidative Stress at 12 months ] [ Designated as safety issue: No ]
    Determine if oxygen radical antioxidant capacity is targeted by rasagiline in patients with ALS.


Estimated Enrollment: 80
Study Start Date: September 2012
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

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

Ages Eligible for Study:   21 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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, 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. 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 blood pressure SBP > 160 mmHg and/or DBP > 95 mmHg.
  18. Use of BiPAP at screening.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01786603

Locations
United States, Arizona
Phoenix Neurological Associates
Phoeniz, Arizona, United States, 85018
United States, California
University of California - Irvine
Irvine, California, United States, 92868
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Missouri
St. Louis University
St. Louis, Missouri, United States, 63104
United States, Nebraska
University of Nebraska
Omaha, Nebraska, United States, 68198
United States, New York
Columbia University
New York, New York, United States, 10032
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
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
  More Information

Responsible Party: Richard Barohn, MD, Gertrude and Dewey Zeigler Professor of Neurology and Chair, University of Kansas Medical Center Research Institute
ClinicalTrials.gov Identifier: NCT01786603     History of Changes
Other Study ID Numbers: 12312  RO1FD003739 
Study First Received: November 28, 2012
Last Updated: May 1, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Rasagiline
Monoamine Oxidase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 25, 2016