None listed
Conditions
Brief summary
The primary purpose of the study is to investigate the effects of 4 different novel pharmacological treatments in the treatment of anorexia nervosa. We hypothesise that there will be a significant difference in a) improvement in AN symptoms from baseline to end of treatment, and 2) increase in BMI from baseline to end of treatment in the 4 groups receiving pharmacological treatment as compared to the control group.
Interventions
ARM 1:
Drug - Memantine hydrochloride
Dose - 20 mg once daily
Duration - 12 weeks
Mode - Oral tablet
ARM 2:
Drug - Brexpiprazole
Dose - 1 mg once daily
Duration - 12 weeks
Mode - Oral tablet
ARM 3:
Drug - Zinc gluconate
Dose - 228.5 mg once daily
Duration - 12 weeks
Mode - Oral tablet
Adherence monitoring:
We'll be asking participants of their adherence during the fortnightly catch-up.
We typically ask:
- Have you missed any pills in the last fortnight? If so, how many
- How many pills do yo
ARM 1: Drug - Memantine hydrochloride Dose - 20 mg once daily Duration - 12 weeks Mode - Oral tablet ARM 2: Drug - Brexpiprazole Dose - 1 mg once daily Duration - 12 weeks Mode - Oral tablet ARM 3: Drug - Zinc gluconate Dose - 228.5 mg once daily Duration - 12 weeks Mode - Oral tablet Adherence monitoring: We'll be asking participants of their adherence during the fortnightly catch-up. We typically ask: - Have you missed any pills in the last fortnight? If so, how many - How many pills do you have left? - If more than 2 pills missed, did you miss these 2 days in a row? - Record any other details The fortnightly catch-up will be conducted by the study doctor or nurse. It will either be a brief 5-10 min phone call or completed in conjunction with a visit to the research site (depending on whether the participant is scheduled to visit the research site that week). Participants will also undertake a nutritional assessment with a dietician at baseline. This assessment should take approximately 30 minutes. Further, those participants who are not already receiving external clinical care will be receiving supportive therapy from trained research staff on a fortnightly basis. This will either be a 30 minute phone or Zoom call or completed in conjunction with a visit to the research site, depending on whether the participant is scheduled to visit the research site that week. Scheduled visits to the research site will take place at Baseline (3 hours), Week 4 (1 hour), Week 8 (1 hour), Week 12. (2.5 hours) There will also be a scheduled follow-up visit to the research site 3 months after having completed the study., which should take approximately 1 hour. Baseline Visit: At the Baseline Visit, the following assessments will be conducted: • The participant will be asked some questions regarding current symptoms of AN, quality of life and readiness to change. • The participant will be required to complete some cognitive tasks that measure thinking (i.e., memory and attention), and decision-making skills. • The participant will be asked to fixate on a fixation cross while being measured using an eye tracker. • A physical examination will be performed by a nurse or the study doctor. • A nutritional assessment, where we ask questions about dietary intake At the end of this session, the study medication will be prescribed. Visits 3 and 4 The participant will be: • asked questions about mood and symptoms • asked about experiences of side effects and any adverse events or health problems since last visit • A physical examination will be performed by a nurse or the study doctor • A blood test to measure liver, kidney, white blood cell, inflammation, glucose, hormones and levels of calcium, magnesium and phosphate .(25 ml) Visit 5: Final Treatment Visit The following assessments will be conducted: • The participant will be asked some questions regarding current symptoms of AN, quality of life and readiness to change. • The participant will be asked whether he/she has experienced any side effects or adverse events. • The participant will be interviewed regarding mood and other symptoms in the past two weeks. • The participant will be asked questions about your quality of life. • The participant will be asked to fixate on a fixation cross while being measured using an eye tracker • A physical examination will be performed by the study doctor. • If completed at baseline, the participant will be required to complete some cognitive tasks that measure thinking (i.e., memory and attention) skills and decision-making skills . • Blood tests and a urine and faecal sample will be collected to assess how symptoms affect biological markers in the blood. These will be compared to the blood tests collected at baseline and throughout the study to assess response to the medication. • A blood test to measure your liver, kidney, white blood cell, inflammation, glucose, hormones and levels of calcium, magnesium, phosphate and zinc (24.5 ml) • A saliva test to measure your cortisol levels (1 x 5 ml). This will be compared to the saliva samples collected at baseline to assess response to the medication. • The participant will be asked to provide a stool sample (can be collected at home or in a private space at the research site, depending on preference) to measure butyrate and zinc levels. • A nutritional assessment, • Cortisol measures will be evaluated via saliva samples (1x 5mL) This will be compared to the saliva samples collected at baseline to assess your response to the medication. The supportive therapy will be administered either by a mental health dietician, psychologist or trained research staff. During supportive therapy sessions, we will check in with you to see how the participant is doing. The sessions will be non-judgemental and led by the participant, and will allow us to establish a good therapeutic alliance and identify your strengths.
Sponsors
Monash University
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of anorexia nervosa (restrictive or binge-eating/purging subtype), in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5). 2. 16 years or older in age. 3. Baseline body mass index (BMI) of equal to or greater than 14 4. Demonstrated capacity to give informed consent. 5. No initiation of therapies targeting AN within the 4 weeks prior to screening. This includes pharmacological and psychological therapies. 6. No increase or initiation of medications with appetite suppressing and/or weight loss effects within the 4 weeks prior to screening. 7. Engagement with a GP at the time of enrolment and over the course of trial participation. 8. Consent for the research team to communicate with the participant’s clinical treatment team in regard to a) Their progress through the trial and b) Communicate clinical deterioration and risks to allow facilitation of appropriate management, where clinically-indicated.
Exclusion criteria
1. Inability to provide informed consent. 2. Hospitalisation within the 2-months prior to screening for the purpose of managing risk of refeeding or treatment of other medical instability that has a causal link with AN. 3. Physical parameters meeting Criteria for Medical Ward Admission as per the The Royal Australian and New Zealand College of Psychiatrists (RANZCP) Alfred Health Eating Disorder – Inpatient Access and Treatment Pathways Guideline, namely: a. High refeeding risk; b. Vital signs as follows: i. Systolic BP < 80 mmHg; ii. Postural BP drop > 20 mmHg systolic, > 10 mmHg diastolic; iii. Heart rate < 40 or > 110; iv. Postural tachycardia >20bpm v. Temperature < 35.5°C. c. ECG changes not overtly benign d. Blood tests within the preceding 7 days showing: i. Blood Glucose <3.0 mmol/L ii. Serum sodium <130 mmol/L iii. Serum magnesium < 0.6 mmol/L iv. Serum potassium <3.0 mmol/L v. Serum phosphate <0.7 mmol/L vi. Glomerular filtration rate < 60ml/min (Cockroft-Gault) vii. Albumin <27 g/L viii. Liver Enzymes ALT > 3 x upper limit of normal ix. Neutrophils <1.0x109/L e. GCS <15 4. Participants who are pregnant or breastfeeding 5. Participants who are taking antipsychotic medication. Antipsychotics that are used as needed may be accepted at the clinical judgement of the investigator. 6. Taking equal to or greater than 4 psychotropic medications at the time of screening. 7. Diagnosed with Type I diabetes, hyperthyroidism, Crohn’s disease or other conditions that reduce weight 8. Other clinically significant cardiac, respiratory, renal, oncological or endocrine conditions, or evidence of medical instability, at the clinical judgement of the investigator. 9. Current substance use meeting DSM-5 criteria for severe substance use disorder. 10. Diagnosis of any other mental disorder that is the participant’s primary diagnosis or main mental health syndrome of concern at the time of screening, which may significantly affect psychiatric status and assessed as likely to impact trial participation, at the clinical judgement of the investigator. 11. Use of any investigational procedure (e.g., clinical trial) within 30 days prior to randomisation. In case of exposure to an investigational medicinal product, the investigator must ensure that it is adequately washed out prior to randomisation (at least 30 days or 5 half-lives of the investigational medicinal product, whatever is longer). 12. Participants with severe and enduring anorexia, defined by an illness duration of at least 7 years.
Outcome results
None listed