Olanzapine for the Treatment of Appetite Loss in Amyotrophic Lateral Sclerosis (ALS)

Charité University Medicine Berlin

Status and phase

Completed

Phase 3

Phase 2

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Treatments

Drug: Olanzapine

Study type

Interventional

Funder types

Other

Identifiers

NCT00876772

OLN-ALS01

Details and patient eligibility

About

Amyotrophic Lateral Sclerosis (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. More than 80% of ALS patients present with a clinically significant and undesirable weight loss. The cause of weight loss is heterogeneous. Fundamentally, the investigators must distinguish malnutrition, cachexia and loss of appetite. Loss of weight is an independent prognosis factor in ALS. Effective treatment of undesirable weight loss 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 employ OLN-induced weight gain or weight stabilization as a symptomatic therapy for the loss of appetite. 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.

Full description

After 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.

Enrollment

40 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients between the ages of 18 and 80 years old
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 a steady dose of RIL 100 mg/day for at least 1 month
A score of ≤ 28 in the symptom-oriented Council on Nutrition appetite questionnaire (CNAQ) by which appetite is evaluated
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
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
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