A randomised, double-blind, placebo-controlled trial to evaluate the efficacy and tolerability of olanzapine as adjunctive treatment for anorexia nervosa in touth: a pilot study

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN23032339
• Date of registration: 04/11/2005
• Prospective Registration: No
• Primary sponsor: Children's Hospital of Eastern Ontario (Canada)
• Public title: A randomised, double-blind, placebo-controlled trial to evaluate the efficacy and tolerability of olanzapine as adjunctive treatment for anorexia nervosa in touth: a pilot study
• Date of first enrolment: 01/09/2005
• Target sample size: 50
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN23032339
• Study type: Interventional
• Study design: Randomised controlled trial (Treatment)

Countries of recruitment

Canada

Contacts

• Name: Wendy Spettigue

Key inclusion & exclusion criteria

Inclusion criteria: 1. Must give written informed consent or assent
2. Must be female
3. Must be between age 12 and 17 (younger than 18) at beginning of trial
4. Based on the Diagnostic and Statistical Manual of Mental Disorders (4th Edition ? Revised, American Psychiatric Association [APA], 2000) must have fulfilled the criteria for diagnosis of Anorexia Nervosa or Eating Disorder Not Otherwise Specified with a Body Mass Index =17
Exclusion criteria: 1. Subject has known sensitivity to any of the products to be administered
2. Treatment with any other anti-psychotic medication, mood stabiliser, stimulant
3. Treatment with medication known to interact with olanzapine e.g. fluvoxamine, ciprofloxacin
4. Medical illness such as: diabetes, impaired glucose tolerance, hyperlipidemia, hepatic dysfunction, substance abuse, narrrow angle glaucoma, paralytic ileus, or pancreatitis
5. Subject?s inability to comply with trial requirements including lack of comprehension of English
6. Other unspecified reasons that, in the opinion of the Investigator, make subject unsuitable for enrollment
7. Subject is pregnant or is breast-feeding
8. Laboratory exclusion criteria:
a. Total white cell count <2.5
b. Neutrophil count <1.0
c. Liver function tests (aspartate transaminase (AST)/alanine transaminase (ALT) >2 X normal)
d. Positive pregnancy test
e. Electrocardiogram (EKG) ? QTc >440 msec or arrythmia other than sinus bradycardia; conduction abnormalities prolonged QTc or other

Age minimum:
Age maximum:
Gender: Female

Health Condition(s) or Problem(s) studied

Anorexia Nervosa
Mental and Behavioural Disorders
Anorexia nervosa

Intervention(s)

Olanzapine versus Placebo; Olanzapine will be started at a very low dose and gradually titrated up to a predetermined dose.

Primary Outcome(s)

The change from baseline in the Eating Attitudes Test (EAT-26) score measured at week 12 and average weight gain over the first 12 weeks of treatment will be compared using Student?s t-test (assuming a normal distribution of the measures; otherwise, Wilcoxon Mann Whitney test will be used). If necessary, a linear regression model will be fit to assess treatment effect adjusting for variables thought to influence outcome that could result in imbalance between treatment groups at baseline. Treatment effect and its 95% confidence interval will be generated for each primary outcome.

Secondary Outcome(s)

Although the study is not powered to detect differences in safety, we will nevertheless compare the frequency of adverse events between the two study groups using chi-square or Fisher?s exact test. Change from baseline in the EAT-26 score measured at week 15 and at the end of the maintenance period (week 40) as well as weight gain measured at the same time points will be analysed as for the primary outcomes. Change from baseline in the Computer Assisted Personal Interview (CAPI), Children?s Depression Inventory (CDI), Multidimensional Anxiety Scale for Children (MASC), the Eating Disorder Clinician-Parent Rating Sheet, and Child Behavior Checklist (CBCL) will be calculated for weeks 12 and 40. Assuming a normal distribution for each variable (except for the clinician/parent rating sheet), differences between study groups will be assessed using Student?s t-tests. Wilcoxon Mann-Whitney tests or log-transformation will be performed otherwise. The Eating Disorder Clinician/Parent Rating Sheet score will also be compared using a Wilcoxon Mann-Whitney test. A Poisson regression model will be used to compare the total number of hospital admissions between study groups. Rate of hospitalisation will be calculated for each patient as the total number of days in hospital divided by the total time in days spent in the study. Average rates and 95% confidence intervals will be generated for each study group. Rates will then be compared using a Poisson regression model. In order to avoid multiple testing issues, results will be compared with an alpha value adjusted for the number of tests performed using the Bonferonni criterion.

Secondary ID(s)

N/A

Source(s) of Monetary Support

W. Garfield Weston Foundation (Canada)