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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2011 by Charite University, Berlin, Germany.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT00876772
First received: April 6, 2009
Last updated: March 23, 2011
Last verified: March 2011
  Purpose

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.


Condition Intervention Phase
Amyotrophic Lateral Sclerosis (ALS)
Drug: Olanzapine
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Placebo-controlled Parallel Group Study for the Evaluation of an Oral Dose of 10mg Olanzapine in Combination With Riluzole for the Treatment of Loss of Appetite in Patients With Amyotrophic Lateral Sclerosis (ALS)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Self-evaluation of appetite by using the Council on Nutrition appetite questionnaire (CNAQ) [ 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 ]
  • Number of patients who have completed treatment with OLN in combination with RIL in comparison with placebo treatment in combination with RIL [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
  • Body Mass Index (BMI) measured in body weight [kg]/(body length [m])2 [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
  • Number of patients with a BMI <18.5 kg/m2 [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
  • Median daily oral food intake in [kcal] which will be determined retrospectively and anamnestically by composing a dietary protocol and by conducting a standardized interview [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
  • Median daily energy balance [kcal] (difference between actual food intake and target food intake)determined retrospectively and anamnestically by composing a dietary protocol and by conducting a standardized interview [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: March 2011
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Olanzapine
    Randomized, 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 Loss of Appetite in patients with amyotrophic lateral sclerosis (ALS)
Detailed 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.

  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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 University, Berlin, Germany, Charité - Universitätsmedizin, Berlin, Germany
ClinicalTrials.gov Identifier: NCT00876772     History of Changes
Other Study ID Numbers: OLN-ALS01
Study First Received: April 6, 2009
Last Updated: March 23, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:
ALS
olanazapine
Loss of Apptetite
Appetite Loss
Malnutrition
Cachexia
Zyprexa

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
TDP-43 Proteinopathies
Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Pathologic Processes
Olanzapine
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents

ClinicalTrials.gov processed this record on August 21, 2014