Olanzapine Versus Placebo for Outpatients With Anorexia Nervosa

Study Overview
=================
Brief Summary
-----------------
Anorexia Nervosa (AN) is a serious illness associated with substantial morbidity and mortality. Weight restoration is a treatment priority, and better treatments are needed.

Detailed Description
-----------------
This study is a 16-week randomized, double-blind, placebo-controlled trial of olanzapine in adult outpatients with AN. 160 individuals with AN, ages > 18, will be randomly assigned to receive olanzapine or placebo for 16 weeks together with a medication management treatment. Primary outcomes will include weight gain as well as psychological symptoms known to be associated with AN, including obsessionality, mood, and anxiety. This project is based on evidence from a recently completed 8-week pilot study comparing the efficacy of olanzapine to placebo in outpatients with AN (PI: Evelyn Attia, MD), as well as a recently published 12-week trial of olanzapine vs placebo (Bissada et al, Am J Psychiatry, 2007) in which outpatient treatment with olanzapine was associated with weight improvement, improved psychological status, and no untoward metabolic effects among low-weight patients. The investigators hypothesize that among underweight adult outpatients with AN receiving olanzapine vs. placebo, together with medication management treatment: 1)patients with AN receiving olanzapine will gain weight at a faster rate than those receiving placebo; and 2) patients with AN receiving olanzapine will demonstrate greater reduction in psychological symptoms, including obsessionality, mood, anxiety and eating disorder symptoms, than those receiving placebo.

Official Title
-----------------
Olanzapine vs Placebo for Outpatients With Anorexia Nervosa

Conditions
-----------------
Anorexia Nervosa

Intervention / Treatment
-----------------
* Drug: Olanzapine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of Anorexia Nervosa Body Mass Index (BMI) between 14.0 and 18.5 kg/m2 Between 18-75 years old Patient not pursuing intensive treatment (inpatient or day treatment) for weight restoration if BMI less than 18 kg/m2 serum potassium > 2.5 mEq/L Exclusion Criteria: Any medical or psychiatric problem requiring medical or psychiatric attention, significant metabolic disturbance upon psychiatrist presentation, and/or significant co-morbid illnesses that are not likely to benefit from proposed treatments or that need specialized treatments for non-eating disorder symptoms. Diabetes mellitus QTc > 480 msec at baseline or increase in QTc of > 35 msec since baseline ECG Significant hyperlipidemia (cholesterol, triglycerides > 1.5 x upper limit of normal) Current diagnosis of substance abuse or dependence Diagnosis of schizophrenia, schizophreniform disorder, bipolar illness (type I) Presence of movement disorder, tardive dyskinesia History of seizure disorder Dementia (subjects over age 55 will be assessed by an MMSE administered by a psychiatrist; those who receive an MMSE score >25 will be excluded) Allergy to olanzapine Documented treatment with 10 mg/day olanzapine x 8 weeks or known inability to tolerate olanzapine 10 mg/day Taking psychotropic (antidepressant, antianxiety, mood stabilizer, antipsychotic) medication within the 4 weeks prior to randomization, other than stable dose of Selective Serotonin Reuptake Inhibitor (SSRI) or Serotonin/Norepinephrine Reuptake Inhibitor (SNRI), or use of benzodiazepine or non-benzodiazepine sleep agents. These permissible medications may be continued during the trial if they have been in use by the patient for a period of > 4 weeks at an unchanged dose without any evidence of consistent weight gain (i.e., > 3 lbs/months) Taking other medication within the last four weeks prior to randomization, known to affect weight (e.g., steroids) Participation in a psychotherapeutic intervention associated with consistent weight gain (i.e. > 3 lbs/month). (Subjects may participate in the study if they are receiving stable outpatient psychotherapy for the 4 weeks prior to randomization as long as there have been no changes in therapy intensity and the psychotherapy has not been associated with weight gain > 3 lbs over the previous 4 weeks. Subjects may also participate if they recently received partial weight restoration treatment in an intensive inpatient or day program as long as they can document that they have not consistently gained weight in their current treatment setting for the 4 weeks prior to baseline screening.)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Control group receiving placebo | Drug: Placebo<br>* Control Group will receive placebo pill<br>|
| Experimental: Olanzapine<br>Group receiving olanzapine | Drug: Olanzapine<br>* Dosing of olanzapine will begin at 2.5 mg and will be titrated to a maximum dose of 10 mg. The target dose of 10 mg of olanzapine was selected because published data from studies that used this dose indicated that it was helpful to patients.<br>* Other names: Zyprexa;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Weight Change | Comparison of rate of weight change between patients receiving olanzapine and those receiving placebo | Weekly during 16-week trial and twice during 8 weeks follow-up | 
| Psychological Change | Comparison of psychological change as measured by the Yale-Brown Obsessive Compulsive Scale (YBOCS), in patients receiving olanzapine compared with those receiving placebo. The Y-BOCS is divided into two sections: obsessive and compulsive. The scores for each section range from 1 to 20. The overall scores are obtained from adding scores for the two sections, to obtain a range between 2-40. A lower score reflects improvement/ fewer obsessive compulsive symptoms. A score of 25 or more is considered moderately severe, a score of 30 or more is considered severe, and a score of more than 35 is considered very severe. | Weekly during 16-week intervention and twice during 8-week follow-up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Eating Disorders, Anorexia Nervosa