Clinical trial NCT06810765: Trifecta Research Study
Official title: Trifecta Research Study: Examining Hormone Replacement Therapy, Magnetic e-Resonance Therapy, Ibogaine, and 5-MeO-DMT in the Treatment of Posttraumatic Stress Disorder and Traumatic Brain Injury-related Cognitive Symptoms
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: PTSD - Post Traumatic Stress Disorder
Cognitive Dysfunction
Brain Trauma
Brain Injuries
Keywords: PTSD
military veteran
cognitive functioning
Traumatic Brain Injury (TBI)
psychedelics
Transcranial Magnetic Stimulation (TMS)
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Special Operators Care Fund
First posted: 2025-02-06
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The Special Operations Care-Fund (SOC-F) will sponsor the application of four treatments - hormone replacement, magnetic resonance brain stimulation, ibogaine, and 5-Meo-DMT - to Special Operations Forces veterans with a history of combat deployments, traumatic brain injury, and problems with mental health and cognitive functioning. An observational study will be conducted in parallel by the Johns Hopkins Center for Psychedelic and Consciousness Research to determine the effectiveness and safety of each treatment, primarily through measuring post-treatment changes in PTSD symptoms and cognitive functioning.

Detailed description: This study uses an interventional design to evaluate the safety and effectiveness of Hormone Replacement Therapy (HRT), Magnetic e-resonance therapy (MeRT), Ibogaine, and 5-methoxy-N,N-dimethyltryptamine (5-Meo-DMT) in the treatment of PTSD and cognitive symptoms associated with combat deployment and traumatic brain injury (TBI) among Special Operations Forces (SOF) veterans. Forty participants will be recruited for this program, which combines state-of-the-art therapies tailored to each individual's needs, aiming to improve psychological and cognitive health outcomes in a population with severe, treatment-resistant conditions.

Participants will be assigned by The Special Operations Care Fund (SOC-F) to one of two sequences of interventions through SOC-F's contracted providers. One group will receive HRT, then MeRT, then Ibogaine and 5-MeO-DMT. The other group will receive HRT, then Ibogaine and 5-Meo-DMT, then MeRT. The study design includes self-reported surveys, informant reports, and cognitive task assessments, all of which will monitor the interventions' impact on participants.

The general purpose is to explore these treatments' potential to promote meaningful symptom improvement and enhanced cognitive function. A combination of subjective and objective data will allow a comprehensive assessment of treatment effectiveness and safety, with the ultimate goal of informing future clinical trials and veteran treatment services.

Specific aims and hypotheses include the following:

Aim 1: Investigate the therapeutic effect of all treatments on PTSD symptoms and cognitive function in SOF veterans with PTSD and cognitive difficulties.

H1. Treatment will be associated with reduced self-reported PTSD symptoms at 3-month follow-up (FU).

H2. Treatment will be associated with improved self-reported cognitive functioning at 3-month follow-up.

H3. Treatment will be associated with improved emotional memory, indexed by the externalizing free recall task, at post-treatment.

Aim 2: Investigate the incremental therapeutic effect of Ibogaine and 5-Meo-DMT on PTSD symptoms and cognitive function relative to HRT and Repetitive Transcranial Magnetic Stimulation (rTMS) therapy in SOF veterans with PTSD and cognitive difficulties.

H4. Ibogaine/5-Meo-DMT will be associated with an incremental reduction in self-reported PTSD symptoms following HRT and rTMS therapy.

H5. Ibogaine/5-Meo-DMT will be associated with an incremental improvement in self-reported cognitive functioning following HRT and rTMS therapy.

H6. Ibogaine/5-Meo-DMT will be associated with an incremental improvement in emotional memory, indexed by the externalizing free recall task, following HRT and rTMS therapy.

Aim 3: Investigate whether the order of interventions differentially impacts PTSD and cognitive symptoms in SOF veterans with PTSD and cognitive difficulties.

No formal hypotheses

Aim 4: Investigate adverse events related to each of the interventions. No formal hypotheses

Eligibility criteria: Inclusion Criteria:

* At least 18 years of age
* Sponsored by SOC-F Program

Exclusion Criteria:

* Diagnosis of Schizophrenia, Bipolar I or II disorder for which patient has been hospitalized or medicated, Depersonalization and/or Derealization Disorder
* Cerebellar dysfunction, Epilepsy, Psychosis or acute confusional state, Dementia
* Prolonged corrected QT interval (QTc) Interval (450ms in males; 470ms in females)
* History of heart failure or hypertrophic heart
* Active blood clots (e.g., Pulmonary embolism, Deep vein thrombosis)
* Major respiratory conditions (e.g., Emphysema, Cystic fibrosis)
* Severe chronic gastrointestinal issues (e.g., bleeding ulcer, leaky gut syndrome)
* Within 6 months of surgeries
* Abnormal blood test results (e.g., potassium or magnesium outside normal range)
* Impaired kidney or liver function
* Refusal to taper off of selective serotonin reuptake inhibitor (SSRI) medication

Primary outcomes:
measure: PTSD Checklist for Diagnostic and Statistical Manual (DSM)-5 (PCL - 5)
timeFrame: Up to 12 months follow up
measure: Medical Outcomes Study Cognitive Functioning Scale (MOS-CF)
timeFrame: UP to 12 months follow up
measure: Externalized Free Recall with Emotional Words
timeFrame: Up to 12 months follow up
measure: Incidence of Adverse Events
timeFrame: Up to 3-months follow-up
measure: Depressive Symptom Index-Suicidality Subscale (DSI-SS)
timeFrame: Up to 12 months follow up
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Center for Psychedelic and Consciousness Research
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Sandeep Nayak, MD
role: PRINCIPAL_INVESTIGATOR
References: