Olanzapine Versus Placebo for Outpatients With Anorexia Nervosa

Anorexia Nervosa Clinical Trial

Official title:

Olanzapine vs Placebo for Outpatients With Anorexia Nervosa

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01170117
• Other study ID #: #6142/7117R
• Secondary ID: R01MH085921
• Status: Completed
• Phase: N/A
• Start date: August 2010
• Est. completion date: June 2017

Study information

• Verified date: May 2018
• Source: New York State Psychiatric Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: June 2017
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.)

Related Conditions & MeSH terms

• Anorexia
• Anorexia Nervosa

Intervention

Drug:
• Olanzapine
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.
• Placebo
Control Group will receive placebo pill

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario
United States	Johns Hopkins	Baltimore	Maryland
United States	New York State Psychiatric Institute	New York	New York
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Weill Cornell Medical Center	White Plains	New York

Sponsors (6)

Lead Sponsor	Collaborator
New York State Psychiatric Institute	Johns Hopkins University, National Institute of Mental Health (NIMH), University of Pittsburgh, University of Toronto, Weill Medical College of Cornell University

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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