An open-label, dose ranging, clinical trial of oral ketamine, an NMDA (N-methyl-D-aspartate) receptor antagonist, with weekly dosing over six weeks in patients who are experiencing post-traumatic stress disorder (PTSD)
This open-label, dose-ranging clinical trial (n=50) aims to determine the feasibility, tolerability, and safety of weekly oral ketamine for PTSD over six weeks with follow-up assessments.
Detailed Description
Open-label, single-group Phase I/II study of once-weekly oral sub-anaesthetic ketamine for six weeks (total 6 dosing sessions) in adults with PTSD; dose starts at 0.5 mg/kg with per-session escalation up to 3.0 mg/kg as tolerated.
Primary outcome is change in PTSD symptomatology measured by the PCL-5 between baseline and follow-up 1; a second follow-up occurs 4 weeks after final treatment. Safety and tolerability are monitored throughout.
Doses are administered onsite by study psychiatrist or delegated MHNP with observation up to 2 hours post-dose; accountability logbook and controlled drug register maintained.
Study Protocol
Preparation
Dosing
Integration
Study Arms & Interventions
Oral ketamine
experimentalOnce-weekly oral sub-anaesthetic ketamine with dose escalation to a tolerated maximum (single-group, uncontrolled).
Interventions
- Ketamine0.5 - 3 mg/kgvia Oral• weekly• 6 doses total
Start 0.5 mg/kg; increase by 0.1–1.0 mg/kg per session as tolerated up to 3.0 mg/kg; continue at 3.0 mg/kg if tolerated.
Participants
Inclusion Criteria
- Current PTSD diagnosis
- Persons (male/female/other) aged over 18 years
- Participants must be able to understand and provide consent on the Participant Information and Consent Form (PICF).
- Participants must be able to tolerate the ketamine treatment, rating scales, blood testing and urinalysis in order to remain in the study and this will be monitored on an ongoing basis.
Exclusion Criteria
- Psychiatric conditions:
- Psychosis
- Mania/hypomania
- Acute suicidality requiring urgent psychiatric intervention
- History of ketamine use disorder
- Physical conditions:
- History of epilepsy or unexplained seizure history
- Uncontrolled/severe symptomatic cardiovascular disease including recent myocardial infarction (within prior 6 months); history of stroke; hypertension (resting BP >150/100)
- Body weight >150 kg
- History of intracranial mass, intracranial haemorrhage/stroke, cerebral trauma/traumatic brain injury or increased intracranial pressure
- Liver function tests out of normal range as specified: ALT >135 U/L; AST >123 U/L; GGT male >210 U/L; GGT female >135 U/L; Total bilirubin >60 µmol/L; Albumin <25 g/L or >150 g/L; ALP >345 U/L
- Previous reaction to ketamine
- Pregnant, breastfeeding, or planning pregnancy during the trial
- Simultaneous participation in another clinical intervention trial
- Participants with a history of substance use disorder (excluding ketamine use disorder) may be eligible only if abstinent from alcohol/illicit substances for two weeks prior and for the remainder of the trial.