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

NCT00876772 | Completed Phase 2

• 1 other identifier: OLN-ALS01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Keywords

ALS; olanazapine; Loss of Apptetite; Appetite Loss; Malnutrition; Cachexia; Zyprexa

Outcome Measures

Primary Outcomes (1)

• Self-evaluation of appetite by using the Council on Nutrition appetite questionnaire (CNAQ)

  1 month

Secondary Outcomes (6)

• Number and severity of adverse events (AE) and severe adverse events (SAE)

  1 month

• Number of patients who have completed treatment with OLN in combination with RIL in comparison with placebo treatment in combination with RIL

  1 month

• Body Mass Index (BMI) measured in body weight [kg]/(body length [m])2

  1 month

• Number of patients with a BMI <18.5 kg/m2

  1 month

• 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

  1 month

Interventions

Olanzapine DRUG

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)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (1)

Charité - Universitätsmedizin, Berlin, Germany

Berlin, 13353, Germany

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Anorexia; Malnutrition; Cachexia

Interventions

Olanzapine

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; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Nutrition Disorders; Weight Loss; Body Weight Changes; Body Weight; Thinness

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Thomas Meyer, MD

  Charité University Hospital, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Thomas Meyer

Study Record Dates

• First Submitted: April 6, 2009
• First Posted: April 7, 2009
• Study Start: March 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: February 14, 2024

Record last verified: 2024-02

Locations

DE (1)