Study of Rasagiline in Patients With Amyotrophic Lateral Sclerosis

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

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.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Rasagiline; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 252
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Department of Neurology, Humboldt University
  • Baden-Württemberg
    • Ulm, Baden-Württemberg, Germany, 89081
      • Department of Neurology, University of Ulm
  • Bayern
    • Muenchen, Bayern, Germany, D-81675
      • Department of Neurology, Technische Universität München
    • Regensburg, Bayern, Germany, D-93053
      • Department of Neurology, Universty of Regensburg
    • Wuerzburg, Bayern, Germany, 91054
      • Department of Neurology, University of Wuerzburg
  • Hessen
    • Wiesbaden, Hessen, Germany, D-65191
      • Department of Neurology, Deutsche Klinik für Diagnostik
  • Mecklenburg-Vorpommern
    • Rostock, Mecklenburg-Vorpommern, Germany, D-18147
      • Department of Neurology, University of Rostock
  • Niedersachsen
    • Goettingen, Niedersachsen, Germany, D-37073
      • Department of Neurology, University of Goettingen
    • Hannover, Niedersachsen, Germany, 30625
      • Department of Neurology, Medical School Hannover
  • Nordrhein-Westfalen
    • Bochum, Nordrhein-Westfalen, Germany, 44789
      • Neurologische Universitätsklinik Bergmannsheil
    • Muenster, Nordrhein-Westfalen, Germany, D-48149
      • Department of Neurology, Universty of Muenster
  • Nordrhrein-Westfalen
    • Bonn, Nordrhrein-Westfalen, Germany, D-53105
      • Department of Neurology, Universty of Bonn
  • Sachsen
    • Dresden, Sachsen, Germany, D-01307
      • Department of Neurology, TU Dresden
  • Sachsen-Anhalt
    • Halle/Saale, Sachsen-Anhalt, Germany, 06097
      • Department of Neurology, University of Halle-Wittenberg
  • Thueringen
    • Jena, Thueringen, Germany, D-07747
      • Department of Neurology, University of Jena

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Ulm
• Investigators: Principal Investigator: Albert C. Ludolph, MD, Prof., Department of Neurology, University of Ulm

Publications and helpful links

General Publications

• Waibel S, Reuter A, Malessa S, Blaugrund E, Ludolph AC. Rasagiline alone and in combination with riluzole prolongs survival in an ALS mouse model. J Neurol. 2004 Sep;251(9):1080-4. doi: 10.1007/s00415-004-0481-5.
• Ludolph AC, Schuster J, Dorst J, Dupuis L, Dreyhaupt J, Weishaupt JH, Kassubek J, Weiland U, Petri S, Meyer T, Grosskreutz J, Schrank B, Boentert M, Emmer A, Hermann A, Zeller D, Prudlo J, Winkler AS, Grehl T, Heneka MT, Wollebaek Johannesen S, Goricke B; RAS-ALS Study Group. Safety and efficacy of rasagiline as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomised, double-blind, parallel-group, placebo-controlled, phase 2 trial. Lancet Neurol. 2018 Aug;17(8):681-688. doi: 10.1016/S1474-4422(18)30176-5. Epub 2018 Jun 19.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: June 12, 2013
• First Submitted That Met QC Criteria: June 12, 2013
• First Posted (Estimate): June 17, 2013

Study Record Updates

• Last Update Posted (Estimate): October 25, 2016
• Last Update Submitted That Met QC Criteria: October 24, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: quality of life; survival; amyotrophic lateral sclerosis; survival time; ALS functioning Rating Scale
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Monoamine Oxidase Inhibitors; Rasagiline
• Other Study ID Numbers: RAS-ALS; 2011-004482-32 (EudraCT Number)