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

Primary Purpose

Amyotrophic Lateral Sclerosis (ALS)

Status

Unknown status

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

Olanzapine

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis (ALS) focused on measuring ALS, olanazapine, Loss of Apptetite, Appetite Loss, Malnutrition, Cachexia, Zyprexa

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Charité - Universitätsmedizin, Berlin, GermanyRecruiting

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

Number of patients with a BMI <18.5 kg/m2

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

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

Full Information

NCT ID

NCT00876772

First Posted

April 6, 2009

Last Updated

March 23, 2011

Sponsor

Charite University, Berlin, Germany

1. Study Identification

Unique Protocol Identification Number

NCT00876772

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2011

Overall Recruitment Status

Unknown status

Study Start Date

March 2011 (undefined)

Primary Completion Date

July 2012 (Anticipated)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

Charite University, Berlin, Germany

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis (ALS)

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Olanzapine

Intervention Description

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)

Primary Outcome Measure Information:

Title

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

Time Frame

1 month

Secondary Outcome Measure Information:

Title

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

Time Frame

1 month

Title

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

Title

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

Time Frame

1 month

Title

Number of patients with a BMI <18.5 kg/m2

Time Frame

1 month

Title

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

Title

Time Frame

1 month

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Thomas Meyer, MD

Phone

+49.30.450660032

thomas.meyer@charite.de

First Name & Middle Initial & Last Name or Official Title & Degree

Teresa Holm, MD

Phone

+49.30.450660218

teresa.holm@charite.de

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thomas Meyer, MD

Organizational Affiliation

Charité University Hospital, Berlin, Germany

Official's Role

Principal Investigator

Facility Information:

Facility Name

Charité - Universitätsmedizin, Berlin, Germany

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Thomas Meyer, MD

Phone

+49.30.450660032

thomas.meyer@charite.de

First Name & Middle Initial & Last Name & Degree

Teresa Holm, MD

Phone

+49.30.450660218

teresa.holm@charite.de

First Name & Middle Initial & Last Name & Degree

Thomas Meyer, MD

12. IPD Sharing Statement

Learn more about this trial

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

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