Clinical trial NCT01184443: Evaluation of the Efficacy and Safety of Olanzapine for Anorexia Nervosa in Children and Adolescents
Official title: Evaluation of the Efficacy and Safety of Olanzapine as an Adjunctive Treatment for Anorexia Nervosa in Children and Adolescents: An Open-label Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Eating Disorder
Keywords: Anorexia Nervosa
Eating Disorder Not Otherwise Specified
Olanzapine
Pediatric
Lead sponsor: Children's Hospital of Eastern Ontario
Sponsor class: OTHER
First posted: 2010-08-19
Enrollment: 38
Sex: ALL
Minimum age (years): 11
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to evaluate the safety and efficacy of the atypical antipsychotic, olanzapine, for the treatment of youth suffering from Anorexia Nervosa (AN).

Adolescent males and females between the ages of 11 and 17 years who are being treated by a physician on the Eating Disorder team at the Children's Hospital of Eastern Ontario will be invited to join the study if they have been diagnosed with AN or Eating Disorder Not Otherwise Specified (EDNOS), and if they weigh less than or equal to 85% of their ideal body weight. Those who meet inclusion and not exclusion criteria, and consent to participating in the trial will be offered adjunctive treatment with olanzapine. Those who agree to take olanzapine will belong to the olanzapine group, and those who decline will belong to the comparison group. Olanzapine doses will be in keeping with the investigators current clinical practice, with flex doses ranging from 1.25 mg to 10.0 mg daily (the majority of patients are treated with 2.5 mg or 5.0 mg at bedtime); dose adjustments made based on individual need and tolerability. Participants will remain in the study for 12 weeks. Those who initially decline olanzapine treatment may change their minds and take olanzapine up until week 9 of the trial.

It is hypothesized that those children and adolescents who choose to take olanzapine at entry into the trial will be more motivated to recover and more compliant with treatment. Compared to those who do not receive medication, it is expected that these adolescents will demonstrate reduced disordered eating attitudes and behaviours, as well as an increased rate of weight gain.

Finally, it is predicted that the rates of discontinuation and the adverse effects of olanzapine will be minor given the relatively low dose (as compared to treatment for patients with schizophrenia), slow titration, and short-term use of olanzapine the investigators will be using.

By comparing the well-being and outcome of patients in the two groups, the investigators hope to begin to answer the question of whether olanzapine does or does not lead to improved clinical outcome for patients with severe eating disorders such as AN or EDNOS, and the question of whether the benefits of using the medication outweigh the risks.


Eligibility criteria: Inclusion Criteria:

* Male or female between 11 and 17 (less than 18) at beginning of trial
* Based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), patient fulfills criteria for diagnosis of Anorexia Nervosa (of which there are two types: restricting or binge-eating/purging) or Eating Disorder Not Otherwise Specified, with a weight of less than or equal to 85% of his or her ideal body weight, as can best be determined at the time of assessment
* Treated by physician on the eating disorder team at the Children's Hospital of Eastern Ontario (CHEO)

Exclusion Criteria:

* Currently receiving treatment with any other antipsychotic medication, mood stabiliser, or stimulant
* Known diagnosis of: diabetes, impaired glucose tolerance, hyperlipidemia, hepatic dysfunction, substance dependence, narrow angle glaucoma, paralytic ileus, or pancreatitis, or any other medical illness that would be considered to significantly impact treatment or recovery from the eating disorder
* Any uncontrolled comorbid disease affecting any system including infectious, endocrine, renal, gastroenterologic, respiratory, cardiac, immunologic, or hematologic. Potential participants with controlled comorbidities in these areas may be invited to participate at the discretion of the primary investigator.
* Experienced one or more seizures without clear and resolved etiology
* Inability to comply with trial requirements including lack of comprehension of English
* Pregnant or breast-feeding
* High blood pressure
* Known allergy or known sensitivity to products in olanzapine
* Other unspecified reasons that, in the opinion of the investigator, amke the patient unsuitable for enrollment
* Officially declared incapable of consenting to treatment under the Mental Health Act (Note: If a patient is involuntarily hospitalized, he or she can be invited to participate provided that he or she has not officially been deemed incapable of making treatment decision under the Mental Health Act)
* Clinically judged to be at serious suicidal ris
* More than 6 months have passed between the patient's initial eating disorder assessment and the time of study entry
* Liver function test (ALT) \> 1.5 x upper limit of normal (ULN)
* Positive pregnancy test
* Electrocardiogram (ECG): QTc \> 450 msec or arrythmia other than sinus bradycardia; conduction abnormalities, prolonged QTc or other
* LDL-C \> 4.9 mmol/L
* Total cholesterol/HDL ratio \> 6
* Fasting glucose \> or equal to 6.1 mmol/L
* Neutrophil count \< 0.5 x 10\^9/L
* Prolactin level at assessment \> 200 ng/mL

Primary outcomes:
measure: Eating Disorder Symptom Severity Scale
timeFrame: 12 weeks
measure: Rate of weight gain
timeFrame: 12 weeks
Secondary outcomes:
measure: Children's Depression Inventory
timeFrame: 12 weeks
measure: Multidimensional Anxiety Scale for Children
timeFrame: 12 weeks
measure: Eating Disorder Examination Questionnaire-Adolescent
timeFrame: 12 weeks
measure: The Children's Eating Attitudes Test
timeFrame: 12 weeks
measure: Child Behavior Checklist
timeFrame: 12 weeks
measure: Eating Disorder Restlessness Agitation Drug Sleep Scale (for youth and parents)
timeFrame: 12 weeks
measure: Eating Disorder Inventory-3
timeFrame: 12 weeks
measure: Overall Safety Profile
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
Study officials:
affiliation: Children's Hospital of Eastern Ontario
name: Wendy J Spettigue, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Spettigue W, Norris ML, Maras D, Obeid N, Feder S, Harrison ME, Gomez R, Fu MC, Henderson K, Buchholz A. Evaluation of the Effectiveness and Safety of Olanzapine as an Adjunctive Treatment for Anorexia Nervosa in Adolescents: An Open-Label Trial. J Can Acad Child Adolesc Psychiatry. 2018 Aug;27(3):197-208. Epub 2018 Jul 1.