Clinical trial NCT01879241: Study of Rasagiline in Patients With Amyotrophic Lateral Sclerosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: amyotrophic lateral sclerosis
survival time
ALS functioning Rating Scale
quality of life
survival
Lead sponsor: University of Ulm
Sponsor class: OTHER
First posted: 2013-06-17
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Survival in ALS-Patients with Rasagiline compared to placebo
timeFrame: 18 Months
Secondary outcomes:
measure: Change of total score of ALS Functional Rating Scale - Revised (ALSFRS-R)
timeFrame: 18 Months
measure: Change of individual Quality of Life (SEIQoL, Schedule for the Evaluation of Individual Quality of Life
timeFrame: 18 Months
measure: Change of slow vital capacity
timeFrame: 18 Months
Other outcomes:
Locations:
city: Ulm
country: Germany
facility: Department of Neurology, University of Ulm
state: Baden-Württemberg
city: Muenchen
country: Germany
facility: Department of Neurology, Technische Universität München
state: Bayern
city: Regensburg
country: Germany
facility: Department of Neurology, Universty of Regensburg
state: Bayern
city: Wuerzburg
country: Germany
facility: Department of Neurology, University of Wuerzburg
state: Bayern
city: Wiesbaden
country: Germany
facility: Department of Neurology, Deutsche Klinik für Diagnostik
state: Hessen
city: Rostock
country: Germany
facility: Department of Neurology, University of Rostock
state: Mecklenburg-Vorpommern
city: Goettingen
country: Germany
facility: Department of Neurology, University of Goettingen
state: Niedersachsen
city: Hannover
country: Germany
facility: Department of Neurology, Medical School Hannover
state: Niedersachsen
city: Bochum
country: Germany
facility: Neurologische Universitätsklinik Bergmannsheil
state: Nordrhein-Westfalen
city: Muenster
country: Germany
facility: Department of Neurology, Universty of Muenster
state: Nordrhein-Westfalen
city: Bonn
country: Germany
facility: Department of Neurology, Universty of Bonn
state: Nordrhrein-Westfalen
city: Halle/Saale
country: Germany
facility: Department of Neurology, University of Halle-Wittenberg
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Department of Neurology, TU Dresden
state: Sachsen
city: Jena
country: Germany
facility: Department of Neurology, University of Jena
state: Thueringen
city: Berlin
country: Germany
facility: Department of Neurology, Humboldt University
Study officials:
affiliation: Department of Neurology, University of Ulm
name: Albert C. Ludolph, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.