Olanzapine for the Treatment of Amyotrophic Lateral Sclerosis (ALS) Cachexia - Full Text View

Sponsored by:	Charite University, Berlin, Germany
Information provided by:	Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:	NCT00876772

Purpose

ALS is an adult neurodegenerative disease that is caused by a selective degeneration of the motor nerve cells in the cortex and myelon. As a result of motor neurodegeneration, a progredient paralysis of the extremities and of the speaking, swallowing, and breathing musculature develops. ALS leads to death by respiratory insufficiency in a mean course of 3-5 years. A clinically significant and undesired weight loss occurs in more than 80% of ALS patients. The weight loss is an independent prognosis factor of ALS. Effective treatment of malnutrition and cachexia is an important therapy goal for ALS.

The researchers propose an investigational therapy of ALS with oral administration of Olanzapine. The rationale for this study is based on the weight-increasing effect of OLN. The clinical trial aims to use the OLN-induced weight gain as symptomatic therapy for ALS cachexia and malnutrition. An undesired weight loss of at least 10% of the body weight should be reduced through the weight-increasing effect of OLN. The hypothesis states that the undesired weight loss in ALS patients during treatment with OLN 10mg in combination with Riluzole (RIL) 100mg is at least 20 percentage points less than for treatment with placebo in combination with 100 mg RIL.

Condition	Intervention	Phase
Amyotrophic Lateral Sclerosis (ALS)	Drug: Olanzapine	Phase II Phase III

Genetics Home Reference related topics: amyotrophic lateral sclerosis

MedlinePlus related topics: Amyotrophic Lateral Sclerosis Weight Control

Drug Information available for: Olanzapine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Randomized, Stratified, Placebo-Controlled, Parallel Group Trial to Evaluate an Oral Dose of 10 mg Olanzapine in Combination With Riluzole for Treatment of Undesired Weight Loss Through Cachexia and Malnutrition in Patients With Amyotrophic Lateral Sclerosis(ALS)

Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:

Body Mass Index (BMI) measured in body weight [kg]/(body length [m])2 [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Number and severity of adverse events (AE) and severe adverse events (SAE) [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	March 2009
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Intervention Details:

Randomized, stratified, placebo-controlled, parallel group trial to evaluate the effectiveness and tolerability of an oral dose of 10 mg Olanzapine in combination with Riluzole for the treatment of undesired weight loss through cachexia and malnutrition in patients with amyotrophic lateral sclerosis (ALS)

Detailed Description:

After stratification and randomization, there is a placebo-controlled parallel group treatment with 10 mg OLN in combination with the standard treatment of Riluzole (100mg/day)(Group 1) in comparison to treatment with placebo in combination with 100 mg RIL (Group 2). Study drug will be provided as 5 mg tablets. OLN will be begun in an initial dosage of 5 mg/day for one week. The intake will occur in the evening hours in the form of a capsule containing 5 mg OLN. The evening dose of Riluzole can be taken together with the OLN medication. After one week (day 8), the dose will be increase to 10 mg OLN/day, which will be taken in the form of two capsules at the same timepoint in the evening hours. This dose will be continued for 51 weeks.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients between the ages of 18 and 80
Clinical diagnosis of definitive, probable, and possible ALS (revised El Escorial Criteria) or diagnosis of the clinical ALS-variants of Progressive Muscle Atrophy (PMA)
Sporadic and familial ALS
Beginning of symptoms of paralysis at least 6 months prior
Treatment with RIL 100 mg/day for at least 1 month
Undesired weight loss > 10% of the body weight within the past 12 months or > 5% of the body weight in 6 months or > 3.5% of the body weight in 3 months or
Undesired weight loss ≥ 5% of the premorbid body weight with a BMI ≤ 20 kg/m2
Progression rate of the degree of ALS severity using the ALS-Functional Rating Scale, revised (ALS-FRS-R) with a monthly change of the ALS-FRS-R (ΔALS-FRS-R/month) of ≥ 0.2/month
Swallowing function with a subscore of the ALS-Functional Rating Scale, revised (ALS-FRS-R) for the evaluation of swallowing function of ≥ 2 and the ALS-Swallowing Severity Scale (ALS-SSS) > 7
Patient consent

Exclusion Criteria:

Patients with known hypersensitivity to OLN, RIL, or one of the active ingredients
Percutaneous Endoscopic Gastronomy (PEG)
Clinically significant eating disorder
Undesired weight loss ≥ 10% of the body weight >12 months before the beginning of paralysis
deliberate weight loss
Underlying consumptive disease with undesired weight loss
Overweight with BMI ≥ 25 kg/m2
Clinically significant hypotonia and history of recurrent syncopes (> 1 syncope)
Clinically severe concomitant illnesses, including psychiatric illnesses
Pregnant or nursing women
Severe neutropenia (<750/mm3)
Open angle glaucoma
Diabetes mellitus
Prostatic hyperplasia
Extrapyramidal movement disorders including from late dyskinesia
Dementia and incompetence to grant informed consent
Clinically significant EKG changes including symptomatic bradycardia
EKG proof of a QT time corrected according to Fridericia (QTcF) > 500 ms
Treatment with substances that are metabolized by the Cytochrom-P450-System CYP1A2 (e. g. Carbamazepine, Fluvoxamin, and Ciprofloxacin)
Treatment with Mirtazapine within the past 3 months
Treatment with steroids or appetite-stimulating substances including anabolics within the past 3 months
Treatment with Valproat within the past 3 months
Treatment with hepatotoxic medicines
Treatment with tetrahydrocannabinol within the past 3 months
Treatment with another atypical or typical neuroleptic within the past 3 months
Treatment with any other study medication < 1 month before the beginning of the study
Destructive use of psychotropic substances within the past 3 months
Destructive use of alcohol
Laboratory parameters outside the normal range that are associated with a clinically significant cardiovascular, pulmonologic, hematologic, hepatological, metabolic, or renal disease or that interfere with interpretation of the clinical study or that require medications that are not permitted in the study protocol
Elevation of the serum transaminase levels (ALT/AST) to more than 3-times of the upper normal value
Elevation of the bilirubin and gamma glutamyl transferase levels (GGT) to beyond the maximum normal value
History of a cardiopulmonary reanimation und prevention of sudden cardiac death
History of clinically significant EKG changes
History of thrombotic events including deep leg vein thrombosis and pulmonary artery embolism
History of a paralytic ileus
History of epilepsy or an episodic seizure

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00876772

Contacts

Contact: Thomas Meyer, MD	+49.30.450660032	thomas.meyer@charite.de
Contact: Teresa Holm, MD	+49.30.450660218	teresa.holm@charite.de

Locations

Germany
Charité - Universitätsmedizin, Berlin, Germany	Recruiting
Berlin, Germany, 13353
Contact: Thomas Meyer, MD +49.30.450660032 thomas.meyer@charite.de
Contact: Teresa Holm, MD +49.30.450660218 teresa.holm@charite.de
Principal Investigator: Thomas Meyer, MD

Sponsors and Collaborators

Charite University, Berlin, Germany

Investigators

Principal Investigator:

Thomas Meyer, MD

Charité University Hospital, Berlin, Germany

More Information

No publications provided

Responsible Party:	Charité - Universitätsmedizin, Berlin, Germany ( Charité University, Berlin, Germany )
Study ID Numbers:	OLN-ALS01
Study First Received:	April 6, 2009
Last Updated:	April 6, 2009
ClinicalTrials.gov Identifier:	NCT00876772 History of Changes
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:

ALS
olanazapine
Malnutrition
Cachexia
Zyprexa

Study placed in the following topic categories:

Neurotransmitter Agents
Spinal Cord Diseases
Olanzapine
Psychotropic Drugs
Antiemetics
Cachexia
Neurodegenerative Diseases
Body Weight
Signs and Symptoms
Malnutrition
Neuromuscular Diseases
Weight Loss
Body Weight Changes
Motor Neuron Disease

Degenerative Motor System Disease
Riluzole
Tranquilizing Agents
Central Nervous System Diseases
Central Nervous System Depressants
Sclerosis
Emaciation
Antipsychotic Agents
Serotonin Uptake Inhibitors
Serotonin
Lou Gehrig's Disease
Amyotrophic Lateral Sclerosis
Peripheral Nervous System Agents

Additional relevant MeSH terms:

Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Spinal Cord Diseases
Physiological Effects of Drugs
Olanzapine
Psychotropic Drugs
Antiemetics
Cachexia
Neurodegenerative Diseases
Body Weight
Signs and Symptoms
Pathologic Processes
Neuromuscular Diseases
Therapeutic Uses

Weight Loss
Body Weight Changes
Motor Neuron Disease
Tranquilizing Agents
Nervous System Diseases
Gastrointestinal Agents
Central Nervous System Diseases
Central Nervous System Depressants
Sclerosis
Emaciation
Antipsychotic Agents
Serotonin Uptake Inhibitors
Pharmacologic Actions
Serotonin Agents
Autonomic Agents

ClinicalTrials.gov processed this record on May 07, 2009