Study of Rasagiline in Patients With Amyotrophic Lateral Sclerosis

NCT01879241 | Completed Phase 2 DMC

• 2 other identifiers: RAS-ALS2011-004482-32
• Study Type: interventional
• Target: 252
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

amyotrophic lateral sclerosis; survival time; ALS functioning Rating Scale; quality of life; survival

Outcome Measures

Primary Outcomes (1)

• Survival in ALS-Patients with Rasagiline compared to placebo

  18 Months

Secondary Outcomes (3)

• 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

Study Arms (2)

Rasagiline

EXPERIMENTAL

Rasagiline 1 mg/day; 18 months

Drug: Rasagiline

Placebo

PLACEBO COMPARATOR

once daily, 18 months

Drug: Placebo

Interventions

Rasagiline DRUG

Rasagiline

Placebo DRUG

a sugar pill manufactured to mimic Rasagiline 1 mg tablet

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Ulm: lead

Study Sites (15)

Department of Neurology, University of Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Department of Neurology, Technische Universität München

Munich, Bavaria, D-81675, Germany

Location

Department of Neurology, Universty of Regensburg

Regensburg, Bavaria, D-93053, Germany

Location

Department of Neurology, University of Wuerzburg

Würzburg, Bavaria, 91054, Germany

Location

Department of Neurology, Deutsche Klinik für Diagnostik

Wiesbaden, Hesse, D-65191, Germany

Location

Department of Neurology, University of Goettingen

Göttingen, Lower Saxony, D-37073, Germany

Location

Department of Neurology, Medical School Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Department of Neurology, University of Rostock

Rostock, Mecklenburg-Vorpommern, D-18147, Germany

Location

Department of Neurology, Universty of Bonn

Bonn, Nordrhrein-Westfalen, D-53105, Germany

Location

Neurologische Universitätsklinik Bergmannsheil

Bochum, North Rhine-Westphalia, 44789, Germany

Location

Department of Neurology, Universty of Muenster

Münster, North Rhine-Westphalia, D-48149, Germany

Location

Department of Neurology, TU Dresden

Dresden, Saxony, D-01307, Germany

Location

Department of Neurology, University of Halle-Wittenberg

Halle, Saxony-Anhalt, 06097, Germany

Location

Department of Neurology, University of Jena

Jena, Thuringia, D-07747, Germany

Location

Department of Neurology, Humboldt University

Berlin, 13353, Germany

Location

Related Publications (2)

• 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.

  PMID: 15372249 BACKGROUND

• 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.

  PMID: 29934198 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

rasagiline

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Albert C. Ludolph, MD, Prof.

  Department of Neurology, University of Ulm

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Prof.

Study Record Dates

• First Submitted: June 12, 2013
• First Posted: June 17, 2013
• Study Start: June 1, 2013
• Primary Completion: April 1, 2016
• Study Completion: August 1, 2016
• Last Updated: October 25, 2016

Record last verified: 2016-10

Locations

DE (15)