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

• Sponsor: Yunxia Wang, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01232738
• Collaborator: Western ALS Study Group (Other)
• Enrollment: 36
• Locations: 10
• Arm: 1
• Duration (Months): 17
• Patients Per Site: 3.6
• 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. 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.

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

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 Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Center Controlled Screening Trial of Safety and Efficacy of Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS)
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) [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)

Secondary Outcome Measures

1. Difference in Time to Treatment Failure [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.

Other Outcome Measures

1. Change in JC-1 Mitochondrial Biomarkers [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.

2. Change in Mitotracker Mitochondrial Biomarkers [Baseline, 6 months, 12 months]

   The 12 month change in mitochondrial biomarkerMitotracker. We measured at baseline, 6 months and 12 months.

3. Change in Percent Annexin V Mitochondrial Biomarkers [Baseline, 6 months, 12 months]

   The 12 month change in mitochondrial biomarker Annexin V %. We measured at baseline, 6 months and 12 months.

4. Change in BCL2/BAX Mitochondrial Biomarkers [Baseline, 6 months, 12 months]

   The 12 month change in mitochondrial biomarker BCL2/BAX. We measured at baseline, 6 months and 12 months.

5. Change in ORAC Mitochondrial Biomarkers [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.

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 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Neurological Institute	Phoenix	Arizona	United States	85018
2	California Pacific Medical Center	San Francisco	California	United States	94118
3	University of Iowa	Iowa City	Iowa	United States	52242
4	University Of Kansas Medical Center	Kansas City	Kansas	United States	66160
5	University of Minnesota	Minneapolis	Minnesota	United States	55414
6	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
7	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
8	University of Tennessee	Memphis	Tennessee	United States	38104
9	The Methodist Hospital System	Houston	Texas	United States	77030
10	McGill University	Montreal	Quebec	Canada	H3A 2B4

Sponsors and Collaborators

• Yunxia Wang, MD
• Western ALS Study Group

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yunxia Wang, MD, Assistant Professor, University of Kansas Medical Center
• ClinicalTrials.gov Identifier: NCT01232738
• Other Study ID Numbers: 11922
• First Posted: Nov 2, 2010
• Last Update Posted: May 18, 2018
• Last Verified: Apr 1, 2018

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

Study Results

Participant Flow

Arm/Group Title	Rasagiline
Arm/Group Description	Open label study of rasagiline at 2 mg daily for 12 months
Period Title: Overall Study
STARTED	36
COMPLETED	23
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Rasagiline
Arm/Group Description	Open label study of 2 mg rasagiline daily
Overall Participants	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.1 (12.0)
Sex: Female, Male (Count of Participants)
Female	19 52.8%
Male	17 47.2%
Region of Enrollment (Count of Participants)
Canada	3 8.3%
United States	33 91.7%

Outcome Measures

1. Primary Outcome

Title	Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R)
Description	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)
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

The placebo arm are from the randomized, controlled studies in ALS performed during 2004-2010, corrected for symptom duration.

Arm/Group Title	ALSRFS-R Slope - Rasagiline	ALSFRS-R - Historical Placebo Control
Arm/Group Description	Change in ALSRFS-R at 12 months	Change in slope in the Historical Placebo Control group
Measure Participants	36	478
Mean (Standard Error) [units on a scale]	-1.20 (0.14)	-0.94 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALSRFS-R Slope - Rasagiline, ALSFRS-R - Historical Placebo Control
	Comments	Difference in slope of decline
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95%; -0.53 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Failure was defined as death, endotracheal intubation, tracheostomy-assisted ventilation, or use of noninvasive ventilation 23 hours/day for 14 days or more. It is defined in years.

Arm/Group Title	Difference in Time to Treatment Failure - Rasagiline	Difference in Time to Treatment Failure - Historical Control
Arm/Group Description	This group is defined as death, endotracheal intubation, tracheostomy-assisted ventilation or noninvasive ventilation >=23 hours/day for 14 days.	Historical Controls were from the previous ALS trials.
Measure Participants	36	203
Median (95% Confidence Interval) [years]	0.9367	0.8963

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALSRFS-R Slope - Rasagiline, ALSFRS-R - Historical Placebo Control
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.58
	Comments
	Method	Log Rank
	Comments

3. Other Pre-specified Outcome

Title	Change in JC-1 Mitochondrial Biomarkers
Description	The 12 month change in mitochondrial biomarkerJC-1 red/green fluorescence ratio. We measured at baseline, 6 months and 12 months.
Time Frame	Baseline, 6 months, 12 months

Outcome Measure Data

Analysis Population Description

Only 14 subjects that completed the study were able to have this biomarker analyzed.

Arm/Group Title	Rasagiline
Arm/Group Description	Open label study of rasagiline at 2 mg daily for 12 months
Measure Participants	14
Mean (95% Confidence Interval) [ratio]	1.92

4. Other Pre-specified Outcome

Title	Change in Mitotracker Mitochondrial Biomarkers
Description	The 12 month change in mitochondrial biomarkerMitotracker. We measured at baseline, 6 months and 12 months.
Time Frame	Baseline, 6 months, 12 months

Outcome Measure Data

Analysis Population Description

Only 17 subjects that completed the study were able to have this biomarker analyzed.

Arm/Group Title	Rasagiline
Arm/Group Description	Open label study of rasagiline at 2 mg daily for 12 months
Measure Participants	17
Mean (95% Confidence Interval) [Relative Fluorescent Intensity]	54.14

5. Other Pre-specified Outcome

Title	Change in Percent Annexin V Mitochondrial Biomarkers
Description	The 12 month change in mitochondrial biomarker Annexin V %. We measured at baseline, 6 months and 12 months.
Time Frame	Baseline, 6 months, 12 months

Outcome Measure Data

Analysis Population Description

Only 17 subjects that completed the study were able to have this biomarker analyzed.

Arm/Group Title	Rasagiline
Arm/Group Description	Open label study of rasagiline at 2 mg daily for 12 months
Measure Participants	17
Mean (95% Confidence Interval) [Annexin V %]	-6.67

6. Other Pre-specified Outcome

Title	Change in BCL2/BAX Mitochondrial Biomarkers
Description	The 12 month change in mitochondrial biomarker BCL2/BAX. We measured at baseline, 6 months and 12 months.
Time Frame	Baseline, 6 months, 12 months

Outcome Measure Data

Analysis Population Description

Only 10 subjects that completed the study were able to have this biomarker analyzed.

Arm/Group Title	Rasagiline
Arm/Group Description	Open label study of rasagiline at 2 mg daily for 12 months
Measure Participants	10
Mean (95% Confidence Interval) [Ratio]	0.24

7. Other Pre-specified Outcome

Title	Change in ORAC Mitochondrial Biomarkers
Description	The 12 month change in mitochondrial biomarker Oxygen Radical Antioxidant Capacity. We measured at baseline, 6 months and 12 months.
Time Frame	Baseline, 6 months, 12 months

Outcome Measure Data

Analysis Population Description

Only 17 subjects that completed the study were able to have this biomarker analyzed.

Arm/Group Title	Rasagiline
Arm/Group Description	Open label study of rasagiline at 2 mg daily for 12 months
Measure Participants	17
Mean (95% Confidence Interval) [Trolox equivalents]	1028.70

8. Other Pre-specified Outcome

Title	Change in ORAC Mitochondrial Biomarkers
Description	The 12 month change in mitochondrial biomarker Oxygen Radical Antioxidant Capacity. We measured at baseline, 6 months and 12 months.
Time Frame	Baseline, 6 months, 12 months

Outcome Measure Data

Analysis Population Description

Only 17 subjects that completed the study were able to have this biomarker analyzed.

Arm/Group Title	Rasagiline
Arm/Group Description	Open label study of rasagiline at 2 mg daily for 12 months
Measure Participants	17
Mean (95% Confidence Interval) [umol Trolox equivalents]	1028.70

9. Other Pre-specified Outcome

Title	Change in ORAC Mitochondrial Biomarkers
Description	The 12 month change in mitochondrial biomarker Oxygen Radical Antioxidant Capacity. We measured at baseline, 6 months and 12 months.
Time Frame	Baseline, 6 months, 12 months

Outcome Measure Data

Analysis Population Description

Only 17 subjects that completed the study were able to have this biomarker analyzed.

Arm/Group Title	Rasagiline
Arm/Group Description	Open label study of rasagiline at 2 mg daily for 12 months
Measure Participants	17
Mean (95% Confidence Interval) [Trolox equivalents]	1028.70

Adverse Events

Arm/Group Title	Rasagiline
Arm/Group Description	Treated for 12 months with rasagiline 2mg orally, once daily. rasagiline: rasagiline 2 mg daily for 12 months
All Cause Mortality
	Rasagiline
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Rasagiline
	Affected / at Risk (%)	# Events
Total	1/36 (2.8%)
Injury, poisoning and procedural complications
Fracture	1/36 (2.8%)	1
Other (Not Including Serious) Adverse Events
	Rasagiline
	Affected / at Risk (%)	# Events
Total	17/36 (47.2%)
Blood and lymphatic system disorders
Dizziness	3/36 (8.3%)	3
Hypertension	1/36 (2.8%)	1
Gastrointestinal disorders
Constipation	2/36 (5.6%)	2
nausea	4/36 (11.1%)	4
General disorders
Xerostomia	1/36 (2.8%)	1
Hepatobiliary disorders
Lab abnormality (elevated ALT)	1/36 (2.8%)	1
Nervous system disorders
Headache	2/36 (5.6%)	2
Psychiatric disorders
Anxiety	2/36 (5.6%)	2
Skin and subcutaneous tissue disorders
Alopecia	1/36 (2.8%)	1

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.