Anorexia Nervosa
Conditions
Keywords
Eating Disorders, Anorexia Nervosa
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.
Interventions
DRUGOlanzapine
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.
DRUGPlacebo
Control Group will receive placebo pill
Sponsors
National Institute of Mental Health (NIMH)
Weill Medical College of Cornell University
University of Pittsburgh
Johns Hopkins University
University of Toronto
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Weight Change | Weekly during 16-week trial and twice during 8 weeks follow-up | Comparison of rate of weight change between patients receiving olanzapine and those receiving placebo |
| Psychological Change | Weekly during 16-week intervention and twice during 8-week follow-up | 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. |
Countries
Canada, United States
Participant flow
Recruitment details
Recruitment took place from December 2010 through June 2016 at each of the five study sites, which are medical clinics: Columbia University-New York State Psychiatric Institute, Weill Cornell Medical College, Centre For Addiction And Mental Health in Toronto, University Of Pittsburgh and Johns Hopkins University.
Pre-assignment details
A total of 25 individuals across sites discontinued the trial prior to group assignment, and 17 were withdrawn by investigators before randomization. These individuals were excluded from the trial due to various reasons such desiring alternate care, and not being interested in medication.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Control group receiving placebo
Placebo: Control Group will receive placebo pill | 77 |
| Olanzapine Group receiving olanzapine
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. | 75 |
| Total | 152 |
Baseline characteristics
| Characteristic | Placebo | Olanzapine | Total |
|---|---|---|---|
| Age, Continuous | 30.0 Years STANDARD_DEVIATION 10.9 | 28.0 Years STANDARD_DEVIATION 10.8 | 29.0 Years STANDARD_DEVIATION 10.9 |
| BMI | 16.69 kg/m2 STANDARD_DEVIATION 1.18 | 16.79 kg/m2 STANDARD_DEVIATION 1.17 | 16.7 kg/m2 STANDARD_DEVIATION 1.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 8 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 71 Participants | 67 Participants | 138 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 71 Participants | 69 Participants | 140 Participants |
| Sex: Female, Male Female | 75 Participants | 71 Participants | 146 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 75 |
| other Total, other adverse events | 0 / 77 | 2 / 75 |
| serious Total, serious adverse events | 13 / 77 | 16 / 75 |
Outcome results
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.
Time frame: Weekly during 16-week intervention and twice during 8-week follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Psychological Change | 0.762 YBOCs score units per month | Standard Deviation 0.375 |
| Olanzapine | Psychological Change | 0.800 YBOCs score units per month | Standard Deviation 0.35 |
Primary
Rate of Weight Change
Comparison of rate of weight change between patients receiving olanzapine and those receiving placebo
Time frame: Weekly during 16-week trial and twice during 8 weeks follow-up
Population: Patients assigned to receive placebo or olanzapine for 16 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Rate of Weight Change | 0.095 kg/m^2 per month | Standard Error 0.053 |
| Olanzapine | Rate of Weight Change | 0.260 kg/m^2 per month | Standard Error 0.051 |