None listed
Conditions
Brief summary
This double-blinded, randomised controlled trial aims to determine the feasibility, tolerability, and safety of intermittent theta burst stimulation (iTBS) and oral ketamine (OK) as a combination treatment for PTSD. Given the complexity and broad range of symptom presentations in patients diagnosed with PTSD, this study seeks to capture changes in sleep quality, perceived stress, suicidality, depression, anhedonia, chronic pain, and social/occupational functioning. Findings from this study will help to identify the brain circuitry involved with and neural processes associated with these glutamatergic and GABAergic-based interventions.
Interventions
This double-blinded, randomised controlled trial (RCT) aims to determine the feasibility, tolerability, and safety of intermittent theta burst stimulation (iTBS) and oral ketamine (OK) as a comination treatment for post-traumatic stress disorder (PTSD). In this 10-week trial, participants will undergo 6 weeks of active treatment followed by 2 follow-up assessments.
Participants will be randomly assigned to one of two study arms:
1.) TMS-OK group: Participants will receive TMS five days a week o
This double-blinded, randomised controlled trial (RCT) aims to determine the feasibility, tolerability, and safety of intermittent theta burst stimulation (iTBS) and oral ketamine (OK) as a comination treatment for post-traumatic stress disorder (PTSD). In this 10-week trial, participants will undergo 6 weeks of active treatment followed by 2 follow-up assessments. Participants will be randomly assigned to one of two study arms: 1.) TMS-OK group: Participants will receive TMS five days a week over a 6-week period (30 TMS treatments total). Participants will receive a sub-anaesthetic dose of oral ketamine (OK) once a week over a 6-week period in a fixed dose of 1 mg/kg of body weight (6 ketamine treatments in total). 2.) TMS-sham + OK group: Participants will receive a sham course of TMS five days a week over a 6-week period (30 sham treatments in total). Participants will receive a sub-anaesthetic dose of oral ketamine (OK) once a week over a 6-week period in fixed dose of 1 mg/kg of body weight (6 ketamine treatments in total). Dosing for Treatment Arm: Oral Ketamine and TMS Oral Ketamine: Participants will receive a sub-anaesthetic dose of oral ketamine (OK) once a week over a 6-week period in fixed dose of 1 mg/kg of body weight (6 ketamine treatments in total). TMS: We will deliver iTBS to the location of the left DLPFC at the intensity of 80% of resting motor with total 20 of 2 second train. Each train will include 10 high frequency bursts (each burst containing 3 pulses at 50Hz) delivering at 5.0 bursts per second (5Hz) for a total of 2 seconds. Both TMS and TMS-sham will be administered on-site by trained research staff (psychiatrist, mental health nurse, registered nurse, research assistants). Each session will take between 20-30 minutes, including set-up, safety check, and treatment. Adherence will be recorded in the source documentation. If a participant is unable to attend or misses a TMS or TMS-sham treatment, they have the opportunity to make up a maximum of 5 sessions. Oral ketamine will be administered on-site by the psychiatrist as per the dosage protocol on routine basis but can be administered by the MHNP as directed by the psychiatrist. The participants will be observed at Thompson Institute for up to two hours after the drug administration. An accountability logbook and controlled drug register (as per Queensland Governmental regulations) for ketamine will be maintained throughout the trial. If a participant is unable to attend or misses a ketamine treatment, details of the deviation will be recorded in the source documentation. Participants will be withdrawn from the study if they miss more than 2 ketamine treatments.
Sponsors
Thompson Institute, University of the Sunshine Coast
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
18 Years to No maximum
Healthy volunteers
No
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, TMS treatment/sham TMS treatment, rating scales, blood testing and urinalysis in order to remain in the study and this will be monitored on an ongoing basis, as per the methodology.
Exclusion criteria
Psychiatric conditions: •Psychosis •Mania/hypomania •Acute suicidality requiring urgent psychiatric intervention •History of ketamine use disorder •History of epilepsy/seizures Physical conditions: •Participants who have active or inactive implants (including device leads), including deep brain stimulators, cochlear implants, and vagus nerve stimulators. •The presence of ferrous metal pins or plates in or near the head (within 30 cm of the coil). Including: implanted electrodes/stimulators, aneurysm clips or coils, stents, or bullet fragments. •Participants who have history of epilepsy or unexplained seizure history. •Participants who have previously undergone TMS treatment. •Uncontrolled/severe symptomatic cardiovascular disease states including: recent myocardial infarction (within prior 6 months); history of stroke; and hypertension (resting blood pressure >150/100) •Body weight of >130kg •History of intracranial mass, intracranial haemorrhage/stroke, cerebral trauma/traumatic brain injury or increased intracranial pressure (as assessed by referring general practitioner) •Liver function test (LFT) results out of normal range, as specified below: •ALT: >135 U/L •AST: >123 U/ •GAMMA GT (GGT) male participants: >210 U/L •GAMMA GT (GGT) – female participants: >135 U/L •TOTAL BILIRUBIN (BIT): >60 umol/L •ALBUMIN (A): <25g/L and >150g/L •ALK PHOS (ALP): >345 U/L •Previous reaction to ketamine (as reported by referring general practitioner and participant) •Participants who have undergone TMS treatment previously •Participants who are pregnant, currently breastfeeding, or who are planning a pregnancy during the trial •Participants who are simultaneously engaging in another clinical intervention trial while participating in TMS-OK PTSD. •Participants with a history of substance use disorder (excluding ketamine use disorder), may be eligible to participate in the study if they abstain from use of the substance two weeks prior to participation in the trial and for the remainder of the trial.
Outcome results
None listed