NCT06810765

Trifecta Research Study

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

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Johns Hopkins University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Conditions

• PTSD - Post Traumatic Stress Disorder
• Cognitive Dysfunction
• Brain Trauma
• Brain Injuries

Interventions

Type	Name	Description
OTHER	Hormone Replacement Therapy (HRT)	Hormone Replacement Therapy (HRT) is a medical treatment that involves restoring healthy endocrine functioning through supplementing or balancing hormones, such as testosterone or estrogen, to address deficiencies caused by injury, aging, or stress.
OTHER	Magnetic Resonance Therapy (MeRT)	MeRT, an EEG (electroencephalography)-guided Repetitive Transcranial Magnetic Stimulation therapy, is a non-invasive treatment that uses magnetic pulses to stimulate specific areas of the brain, guided by an individual's brain patterns. MeRT is a neuromodulatory tool that has shown therapeutic efficacy in relation to a number of psychopathological targets including PTSD, depression, and TBI-related cognitive impairment through promoting cortical excitability, modulating neurotransmission, and restoring neuroplasticity.
DRUG	ibogaine with magnesium treatment	Ibogaine, an indole alkaloid that interacts with mu opioid, kappa opioid, N-methyl-D-aspartate receptor (NMDA), and nicotinic acetylcholine receptors, shows early signs of effectiveness as a rapid-acting treatment for a number of mental health disorders including addiction. It is believed to work by promoting neuroplasticity and modulating brain chemistry, which may help reset dysfunctional neural circuits. The treatment is unique in its psychoactive properties, offering a deeply introspective experience that may help individuals process emotional material from the individual's lives.
DRUG	5-MeO-DMT	5-MeO-DMT, as described in the study, is a 5-HT 2A agonist compound used in previous clinical research to address depression. Unlike other treatments, 5-MeO-DMT acts rapidly and has a short duration of action, offering an intense but time-limited psychoactive state. Its potential to enhance neuroplasticity and recalibrate dysfunctional brain networks makes it a unique approach for addressing the complex interplay of psychological and neurological symptoms.

Timeline

• Start date: 2025-09-01
• Primary completion: 2026-12-01
• Completion: 2027-12-01
• First posted: 2025-02-06
• Last updated: 2025-08-22

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study