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

• ClinicalTrials.gov Identifier: NCT01232738
• Recruitment Status: Completed
• First Posted: November 2, 2010
• Results First Posted: May 18, 2018
• Last Update Posted: May 18, 2018
• Sponsor: Yunxia Wang, MD
• Collaborator: Western ALS Study Group
• Information provided by (Responsible Party): Yunxia Wang, MD, University of Kansas Medical Center

Tracking Information

• First Submitted Date: October 22, 2010
• First Posted Date: November 2, 2010
• Results First Submitted Date: November 16, 2016
• Results First Posted Date: May 18, 2018
• Last Update Posted Date: May 18, 2018
• Study Start Date: December 2011
• Actual Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 17, 2018)

Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) [ Time Frame: up to 12 months ]

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)

Original Primary Outcome Measures (submitted: October 29, 2010)

The primary outcome measure is the difference in the rate of decline in function. [ Time Frame: up to 12 months ]

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.

Current Secondary Outcome Measures (submitted: April 17, 2018)

Difference in Time to Treatment Failure [ Time Frame: up to 12 months ]

This group is defined as death, endotracheal intubation, tracheostomy-assisted ventilation or use of noninvasive ventilation >= 23 hours/day for 14 days or more.

Original Secondary Outcome Measures (submitted: October 29, 2010)

Measure Disease progression [ Time Frame: up to 12 months ]

Secondary Outcome measures include: changes in disease progression rate as measured by pulmonary function (the rate of decline of vital capacity, percent predicted), quality of life, safety, and survival (mortality combined with initiation of mechanical ventilations).

Current Other Pre-specified Outcome Measures (submitted: April 17, 2018)

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

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial of Safety and Efficacy of Rasagiline in Patients With Amyotrophic Lateral Sclerosis (ALS)
• Official Title: A Multi-Center Controlled Screening Trial of Safety and Efficacy of Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS)

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. 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.

• 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
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Amyotrophic Lateral Sclerosis (ALS)

Intervention

Drug: rasagiline

rasagiline 2 mg daily for 12 months

Study Arms

Experimental: rasagiline

Treated for 12 months with rasagiline 2mg orally, once daily.

Intervention: Drug: rasagiline

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 17, 2018): 36
• Original Estimated Enrollment (submitted: October 29, 2010): 60
• Actual Study Completion Date: May 2013
• Actual Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)

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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT01232738
• Other Study ID Numbers: 11922
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Yunxia Wang, MD, University of Kansas Medical Center
• Original Responsible Party: Yunxia Wang, MD, University Of Kansas Medical Center
• Current Study Sponsor: Yunxia Wang, MD
• Original Study Sponsor: University of Kansas
• Collaborators: Western ALS Study Group

Investigators

• Principal Investigator: Yunxia Wang, MD; University of Kansas Medical Center

• PRS Account: University of Kansas Medical Center
• Verification Date: April 2018