Treatment of depressive symptoms in people with anorexia nervosa (duration of at least 3 years) and comorbid severe depression that has not responded to at least one treatment. Mental and Behavioural Disorders
Conditions
Interventions
60 participants will be randomised (1:1) to receive four weeks of oral ketamine 60-180mg (2 x weekly) or placebo. Trial participation will consist of three phases: i) screening, ii) dosing sessions (c
Keticap® Immediate Release, manufactured by Neurocentrx Ltd.) or placebo, twice weekly for a total of four weeks. KET-IR is a novel formulation of immediate-release ketamine hydrochloride within a HP
Sponsors
King's College London
South London and Maudsley NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent form 2. SE-AN as defined by i) a primary diagnosis of AN as specified in the International Classification of Diseases (ICD)-11 and ii) at least 3 years history of AN (since diagnosis), based on medical records, clinical assessment, BMI, MINI at screening 3. Severe depression with a failed treatment attempt, as defined by i) severe depression as specified in the ICD-11 and ii) non-response or failure to achieve remission after one or more treatments recommended by NICE for severe depression. 4. Aged 18 years old or above at screening 5. Capacity to consent 6. Screening Body Mass Index (BMI) =14kg/m² 7. Weight above 40kg 8. At low risk for suicidality as assessed by the research team 9. Medically stable as determined by screening: clinical interview, clinical laboratory values, vital signs, ECG and medical history. 10. Agreement to follow the contraception requirements of the study. 11. Registered with a General Practitioner (GP) in the UK, and agreement for the team to maintain contact with the GP and/or specialist ED team for the duration of the study.
Exclusion criteria
Exclusion criteria: 1. Cardiovascular conditions, including stroke, myocardial infarction or clinically significant arrythmia within 1 year of screening, uncontrolled hypertension, bradycardia, abnormalities on ECG (e.g., elongated QT interval corrected by Fridericia), based on an assessment of medical history and ECG and vital signs at screening. 2. Clinically significant abnormalities in laboratory tests at screening, including full blood count, total bilirubin, creatinine, glomerular filtration rate (GFR), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). 3. Any other clinically significant physical illness or contraindication (e.g. but not limited to, renal, hepatic, pulmonary, cardiovascular, gastrointestinal) that the investigator deems may interrupt the participation in the study or pose a health risk for the participant if they were to take part in the study. 4. Relevant neurological comorbidity, in particular dementia; lifetime seizures; epilepsy; increased intracranial pressure. 5. Recent heart or head surgery. 6. Significant weight loss (=2kg) in the month before screening. 7. Weight loss of over 1kg per week between screening and baseline. 8. (For females of childbearing potential) Unwillingness to follow the contraceptive requirements of the study, and to take pregnancy tests throughout the study. 9. (For females) Current breastfeeding. 10. Recent illicit drug use as determined by urine drug screening at the screening visit. 11. Hypersensitivity to the study drug (KET-IR or placebo) or any of its excipients 12. Dosage in any investigational drug or device study within three months of screening or any other study that may constitute a contraindication for taking ketamine. 13. Blood or needle phobia. 14. No email access. 15. Previous or current alcohol or substance use disorder as assessed by medical history, the MINI, ASSIST and urine toxicology at screening. 16. Previous or current psychotic disorder or bipolar disorder, as assessed by a review of medical history and the MINI. 17. Previous or current schizoid, schizotypal, paranoid, histrionic, antisocial or narcissistic personality disorder, as based on medical history, the Standardised Assessment of Personality (SAPAS), the Personality Assessment Questionnaire for DSM-11 (PSQ-11) and clinical judgment 18. Current panic disorder or panic attacks/episodes within the past year, as determined by the MINI and clinical judgment 19. Significant suicide risk at screening, as assessed by suicidal behaviours during the previous year as assessed through clinical interview and medical records; suicidal ideation or significant suicidal risk expressed in the C-SSRS or during clinical interview. 20. Self-reported exposure to ketamine therapeutically or recreationally within the past six months. 21. Use of contraindicated medications as listed in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Study feasibility: 1. Recruitment (expressed as total number recruited as percentage of the required sample size), at end of study 2. Lost to follow up rate, expressed as percentage who withdraw from data collection out of number randomised, by study arm, at end of study; and 28-days [primary], 3 months and 6 months, [secondary] 3. Assessment response rate (expressed as percentage of questionnaires fully completed, by study arm), at end of study; and 28-days [primary], 3 months and 6 months, [secondary] 4. Proportion who remained on the intervention (Ketamine or Placebo) (expressed as a percentage, by study arm), at end of study; and 28-days [primary], 3 months and 6 months, [secondary] 5. Adherence to treatment (expressed as a proportion of participants who take 60% of total prescribed dose; by study arm), at end of study; and 28-days [primary], 3 months and 6 months, [secondary] | — |
Secondary
| Measure | Time frame |
|---|---|
| Study acceptability 1. Likert scales of acceptability (measured as a final value; expressed as a mean±standard deviation, per study arm) at end of study 2. Perceived acceptability of interventional medicinal product and study design (from qualitative interviews, expressed as theme/subtheme, per study arm) at end of study Exploratory preliminary assessment (descriptive only; no hypothesis testing will be carried out) of clinical measures: 3. Change in depression scores (MADRS change; measured as a change from baseline; expressed as a mean±standard deviation, per study arm) at 28 days [primary], 3 months and 6 months [secondary] 4. Change in eating disorder psychopathology (EDE-Q; measured as a change from baseline; expressed as a mean±standard deviation, per study arm) at 28 days [primary], 3 months and 6 months [secondary] 5. Change in quality of life (EQ-5D-5L; measured as a change from baseline; expressed as a mean±standard deviation, per study arm) at 28 days [primary], 3 months and 6 months [secondary] Exploratory assessment (descriptive only; no hypothesis testing will be carried out) of safety and tolerability, at end of study 6. Incidence of adverse events (measured as a final value; expressed as a percentage who experienced in each arm, split by whether or not an SAE, relatedness to study drug and body system), at end of study 7. Incidence of side effects (measured as a final value per side effect category; expressed as a total sum, per study arm), at end of study | — |
Countries
England, United Kingdom
Contacts
Public ContactJohanna Keeler
Outcome results
None listed