Clinical trial NCT01170117: Olanzapine Versus Placebo for Outpatients With Anorexia Nervosa
Official title: Olanzapine vs Placebo for Outpatients With Anorexia Nervosa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Anorexia Nervosa
Keywords: Eating Disorders
Anorexia Nervosa
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: Weill Medical College of Cornell University
name: University of Pittsburgh
name: Johns Hopkins University
name: University of Toronto
First posted: 2010-07-27
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.)

Primary outcomes:
measure: Rate of Weight Change
timeFrame: Weekly during 16-week trial and twice during 8 weeks follow-up
measure: Psychological Change
timeFrame: Weekly during 16-week intervention and twice during 8-week follow-up
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
city: White Plains
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: New York State Psychiatric Institute
name: Evelyn Attia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bissada H, Tasca GA, Barber AM, Bradwejn J. Olanzapine in the treatment of low body weight and obsessive thinking in women with anorexia nervosa: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry. 2008 Oct;165(10):1281-8. doi: 10.1176/appi.ajp.2008.07121900. Epub 2008 Jun 16.
citation: Attia E, Steinglass JE, Walsh BT, Wang Y, Wu P, Schreyer C, Wildes J, Yilmaz Z, Guarda AS, Kaplan AS, Marcus MD. Olanzapine Versus Placebo in Adult Outpatients With Anorexia Nervosa: A Randomized Clinical Trial. Am J Psychiatry. 2019 Jun 1;176(6):449-456. doi: 10.1176/appi.ajp.2018.18101125. Epub 2019 Jan 18.