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)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01232738

Enrollment

Registered

2010-11-02

Start date

2011-12-31

Completion date

2013-05-31

Last updated

2018-05-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Interventions

DRUGrasagiline

rasagiline 2 mg daily for 12 months

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

21 Years to 80 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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.
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.
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.
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.

Countries

Canada, United States

Participant flow

Participants by arm

Arm	Count
Rasagiline Open label study of 2 mg rasagiline daily	36
Total	36

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	5
Overall Study	Death	3
Overall Study	Lost to Follow-up	1
Overall Study	Physician Decision	2
Overall Study	Withdrawal by Subject	2

Baseline characteristics

Characteristic	Rasagiline
Age, Continuous	61.1 years STANDARD_DEVIATION 12
Region of Enrollment Canada	3 Participants
Region of Enrollment United States	33 Participants
Sex: Female, Male Female	19 Participants
Sex: Female, Male Male	17 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	17 / 36
serious Total, serious adverse events	1 / 36

Outcome results

Primary

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)

Time frame: up to 12 months

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

Arm	Measure	Value (MEAN)	Dispersion
ALSRFS-R Slope - Rasagiline	Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R)	-1.20 units on a scale	Standard Error 0.14
ALSFRS-R - Historical Placebo Control	Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R)	-0.94 units on a scale	Standard Error 0.04

Comparison: Difference in slope of declinep-value: 0.0795% CI: [-0.53, 0.02]Chi-squared

Secondary

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.

Time frame: up to 12 months

Population: 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	Measure	Value (MEDIAN)
ALSRFS-R Slope - Rasagiline	Difference in Time to Treatment Failure	0.9367 years
ALSFRS-R - Historical Placebo Control	Difference in Time to Treatment Failure	0.8963 years

p-value: 0.58Log Rank

Other Pre-specified

Change in BCL2/BAX Mitochondrial Biomarkers

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