Title: Olanzapine for young PEople with aNorexia nervosa: An open-label feasibility study to test recruitment, treatment acceptance, adherence, safety, outcome measures and patients' experience to prepare for a randomised placebo-controlled trial (OPEN)
Funder: Department of Health and Social Care

Abstract: The present treatments for anorexia are not really helping severely ill people with anorexia. Many doctors prescribe medications that are not approved for treating anorexia; however, it is unclear whether these drugs are safe or help at all._x000D_ _x000D_ We talked to patients, their families and leading experts about their views on drugs that could help with anorexia and have evaluated what has been written on the subject by experts. Olanzapine appears to be a helpful and safe medication; it may help with anorexic thoughts, low mood, sleep and anxieties, which are considered important factors for patients. Olanzapine has also been shown to help increase weight gain; however, further evidence is required. It is not currently approved for anorexia._x000D_ _x000D_ We gathered a team with strong expertise in anorexia and mental health medicines. The team includes patients with lived experience of anorexia. Researchers from Sydney would like to join us and perform an additional component of this project in Australia. Nine NHS Trusts and two Australian eating disorder services will be used as treatment centres. The Australian arm of the study is funded by the National Health and Medical Research Council._x000D_ _x000D_ At present, we do not know whether a sufficient number of patients with anorexia would consider taking olanzapine or take part in a study assessing olanzapine. How long patients might adhere to this medication is also unclear. Thus, we are planning to perform a preliminary study with 70 patients (55 female or male patients with anorexia in the UK plus 15 patients in Australia), who are aged 12–24 years, can safely take olanzapine and have not gained sufficient weight under specialist treatment. We recommend patients take olanzapine for a 12-month period in the study._x000D_ _x000D_ We will determine how many patients need to be asked to recruit 70, who will agree to take part, receive olanzapine as a normal prescription alongside their usual treatment, and assess whether olanzapine has helped them. For adolescent patients, their parents or guardians will also need to provide consent for their involvement._x000D_ _x000D_ In addition to questionnaires, physical examinations and laboratory investigations are planned. A researcher will have in-depth talks with the study participants to find out about their experience, why they agreed/did not agree to olanzapine, and why they took it for 12 months or stopped. Patients will be examined after 8 and 16 weeks, after 6 months and after 12 months. At each time point, doctors will review the treatment together with the patients and make a decision on whether to continue with olanzapine. After this preliminary study, we will be able to determine whether the methods we intend to use to measure outcomes work. These outcomes are change in body weight, negative thoughts, low mood, anxiety and sleep, unwanted effects of olanzapine, and patients’ and carers’ quality of life. The patients will also be asked whether they would take part in a study in which they would receive either olanzapine or a dummy pill (placebo) without knowing which one._x000D_ _x000D_ Once we have the above information, we can prepare a larger study with >300 participants. This number will be necessary to draw firm conclusions. Our findings will be published in journals in cooperation with patients with anorexia, and presented at patients’ and carers’ meetings, and scientific conferences. Interested participants will be kept up-to-date with the study progress. Before applying for this larger study, we will discuss the full research plan with patients, carers and experts.

Lay abstract: Research Question: For young people with anorexia nervosa (AN), is it feasible to conduct a trial to examine the benefits and harms of prescribing olanzapine to those who have not responded to first-line treatments?_x000D_ _x000D_ Design: Feasibility study; open treatment of 70 patients (55 in the UK, 15 in Australia) with olanzapine for 12 months. Participants will be examined at baseline, and at 8 weeks, 16 weeks, 6 months and 12 months after start of treatment. The Australian arm of the study is funded by the National Health and Medical Research Council (NHMRC)._x000D_ _x000D_ Setting: Specialist eating disorder services for adolescents and adults._x000D_ _x000D_ Team:_x000D_ • Eating disorder specialists for adults and adolescents_x000D_ • Researchers_x000D_ • People with lived experience of AN_x000D_ _x000D_ Aims:_x000D_ • To assess the proportion of patients in different treatment settings who: _x000D_ - agree to take olanzapine unblinded and under real-life conditions_x000D_ - adhere to olanzapine_x000D_ - complete all study assessments and questionnaires at the five assessment points_x000D_ • To examine different methods to measure adherence_x000D_ • To study patients’ experience of recruitment and treatment, reasons for adherence and non-adherence_x000D_ • To examine and document what treatment as usual (TAU) means in practice _x000D_ • To examine adverse effects and safety_x000D_ • To assess willingness to participate in a randomised-controlled trial (RCT; blinded, placebo-controlled)_x000D_ _x000D_ Study sample:_x000D_ • 70 patients (55 UK, 15 Australia, 12–24 years, males and females) with the inclusion criteria: _x000D_ - Adolescent or young adult inpatients, day-care or outpatients with AN_x000D_ - Inadequate response to first-line treatments, defined by <2 kg weight gain within at least one month_x000D_ • Exclusion criteria:_x000D_ - Serious self-harm, suicidality or harm to others_x000D_ - Serious medical comorbidities, seriously abnormal laboratory parameters or ECG _x000D_ - Contraindications for olanzapine. _x000D_ _x000D_ Intervention: _x000D_ Olanzapine (dose: 1.25–10 mg/d) plus TAU for 12 months prescribed off-label as normal_x000D_ _x000D_ Outcomes: _x000D_ • Recruitment and willingness to take olanzapine and adhere to it_x000D_ • Patients’ experience of recruitment and treatment, reasons for adherence and non-adherence_x000D_ • Elements of TAU in practice_x000D_ • Feasibility of questionnaires, assessments (incl. BMI) and adherence measures_x000D_ • Adverse effects and safety_x000D_ • Willingness to participate in an RCT (blinded, placebo-controlled)_x000D_ _x000D_ Analyses: _x000D_ • Summary statistics related to: _x000D_ - Patients approached, screened and included in the study_x000D_ - Adherence and the return of completed assessments and questionnaires_x000D_ - Willingness to take part in an RCT_x000D_ - Elements that constitute TAU_x000D_ - Adverse effects _x000D_ • Qualitative analysis: Patients’ experience (recruitment, treatment, reasons for adherence and non-adherence)_x000D_ _x000D_ Dissemination and projected outputs:_x000D_ • Registration with trial registries_x000D_ • Presentation of findings at national/international conferences, charities, service user & carers meetings_x000D_ • Publication of design/findings: KCL/NHS press offices, scientific journals, NIHR HTA Journal_x000D_ • Interested participants to be routinely informed about the study_x000D_ _x000D_ Project timetable: _x000D_ • Before project start: Manuals, consent and participant information sheets, ethics_x000D_ • Months 0–6: Site training, set-up_x000D_ • Months 0–12: Recruitment: N=70 (55 UK, 15 Australia)_x000D_ • Month 1–19: Assessments and treatment with olanzapine + TAU, documentation and reporting_x000D_ • Month 20: Data evaluation, writing reports, publications_x000D_ • After project: If feasibility study is successful: _x000D_ - PPI consultation_x000D_ - Application for pilot/RCT

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH