Clinical TrialDepressive DisordersKetaminePlaceboRecruiting
Ketamine for the treatment of depression with anorexia nervosa
This randomised, double-blind, placebo-controlled Phase II trial (n=60) will study the feasibility, safety, and acceptability of oral ketamine (60–180 mg, administered twice weekly) as a treatment for adults with long-standing anorexia nervosa and comorbid treatment-resistant depression.
Target Enrollment
60 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind
Registry
Detailed Description
Randomised, single-centre, double-dummy, quadruple-blind feasibility trial (EDEN) comparing oral KET-IR (60–180 mg) versus placebo, dosed twice weekly for four weeks (eight supervised in-person dosing sessions).
Primary outcomes focus on feasibility metrics (recruitment, retention, adherence); exploratory clinical measures include MADRS for depression, EDE-Q for eating disorder psychopathology, quality of life (EQ-5D-5L), and safety/tolerability.
Study Protocol
Preparation
sessions
Dosing
8 sessions
Integration
sessions
Study Arms & Interventions
KET-IR
experimentalOral immediate-release ketamine (KET-IR) titrated 60→120→180 mg, double-dummy; twice-weekly for 4 weeks.
Interventions
- Ketamine60 - 180 mgvia Oral• twice weekly• 8 doses total
KET-IR (60 mg capsules); participants ingest 1–3 capsules (60–180 mg) with double-dummy to total 3 capsules; dose may escalate after safety review.
Placebo
inactiveVisually identical placebo capsules, double-dummy, twice-weekly for 4 weeks.
Interventions
- Placebovia Oral• twice weekly• 8 doses total
Three visually identical capsules (placebo) using double-dummy approach; mirrors experimental arm schedule.
Participants
Ages
18 – 99
Sexes
Male & Female
BMI
14 - +
Psychosis History
-
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
- 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.
Study Details
- StatusRecruiting
- PhasePhase II
- Typeinterventional
- DesignRandomizedquadruple Blind
- Target Enrollment60 participants
- TimelineStart: 2025-06-12End: 2028-05-01
- Compounds
- Topic
Locations
King's College London — London, United Kingdom