Study of Rasagiline in Patients With Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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The primary objective of the trial is to investigate the survival time (the time from randomization until death or end of the trial) compared between control group and experimental group. This is a prospective, multicenter, randomized, stratified, parallel-group, double-blind trial comparing placebo with 1 mg/d rasagiline as add-on therapy to 100 mg riluzole in amyotrophic lateral sclerosis (ALS) in 250 enrolled patients. For entry, the El Escorial Criteria for the diagnosis of ALS will be used. The patients have to be stable on riluzole at least 4 weeks prior to randomization.

Official Title
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Efficacy, Safety and Tolerability Study of 1 mg Rasagiline in Patients With Amyotrophic Lateral Sclerosis (ALS) Receiving Standard Therapy (Riluzole) - An AMG Trial With a Market Authorized Substance

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: Rasagiline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Possible, probable (clinically or laboratory) or definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria Disease duration more than 6 months and less than 3 years (inclusive). Disease onset defined as date of first muscle weakness, excluding fasciculations and cramps Vital capacity more than 50% of normal (slow vital capacity; best of three measurements) Age: ≥ 18 years Continuously treated with 100 mg riluzole for at least four weeks Capable of thoroughly understanding all information given and giving full informed consent according to GCP Women of childbearing age must be non-lactating and surgically sterile or using a highly effective method of birth control and have a negative pregnancy test. Acceptable methods of birth control with a low failure rate i.e. less than 1% per year) when used consistently and correct are such as implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), or double-barrier methods (condom or diaphragm with spermicidal agent or IUD), sexual abstinence or vasectomized partner Exclusion Criteria: Previous participation in another clinical study within the preceding 12 weeks Tracheostomy or assisted ventilation of any type during the preceding three months Gastrostomy Any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS Presence of any concomitant life-threatening disease or impairment likely to interfere with functional assessment Patients on sympathomimetic agents. This includes pseudoephedrine, phenylephrine, phenylpropanolamine, and ephedrine. Patients on analgesics with serotoninergic properties such as meperidine, tramadol, methadone and propoxyphene. Patients on serotonin reuptake inhibitors (SSRIs). This includes fluoxetine or fluvoxamine. Patients on dextromethorphan, St. John's wort, cyclobenzaprine or other MAO inhibitors (selective or non-selective) Patients taking Antidepressants Confirmed hepatic insufficiency or abnormal liver function (ASAT and/or ALAT greater than 3 times the upper limit of the normal range) Renal insufficiency (serum creatinine more than 2.26 mg/dL) Evidence of major psychiatric disorder or clinically evident dementia precluding evaluation of symptoms Known hypersensitivity to any component of the study drug Liable to be not cooperative or comply with the trial requirements (as assessed by the investigator), or unable to be reached in the case of emergency Female with childbearing potential, if no adequate contraceptive measures are used Pregnancy or breast-feeding females

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rasagiline<br>Rasagiline 1 mg/day; 18 months | Drug: Rasagiline<br> <br> |
| Placebo Comparator: Placebo<br>once daily, 18 months | Drug: Placebo<br>* a sugar pill manufactured to mimic Rasagiline 1 mg tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival in ALS-Patients with Rasagiline compared to placebo |  | 18 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of total score of ALS Functional Rating Scale - Revised (ALSFRS-R) |  | 18 Months | 
| Change of individual Quality of Life (SEIQoL, Schedule for the Evaluation of Individual Quality of Life |  | 18 Months | 
| Change of slow vital capacity |  | 18 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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survival time, amyotrophic lateral sclerosis, ALS functioning Rating Scale, quality of life, survival