Trifecta Research Study

NCT06810765 | Withdrawn Phase 2 FDA Drug FDA Device

• 1 other identifier: IRB00473770
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

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)

Outcome Measures

Primary Outcomes (5)

• PTSD Checklist for Diagnostic and Statistical Manual (DSM)-5 (PCL - 5)

  The PTSD Checklist for DSM-5 (PCL-5) is a self-report questionnaire designed to assess the severity of PTSD symptoms in alignment with the DSM-5 diagnostic criteria. A total symptom severity score (range - 0-80) can be obtained by summing the scores for each of the 20 items with higher scores indicating greater symptom severity. Collected - Group 1: Baseline, pre-HRT, pre-MeRT, mid-MeRT (week 3 MeRT), pre-Ibo/5Meo, post-Ibo/5Meo, 3 month follow up (MFU), 6 MFU, 12 MFU; Group 2: Baseline, pre-HRT, pre-Ibo/5Meo, pre-MeRT, mid-MeRT, Post-MeRT, 3 MFU, 6 MFU, 12 MFU

  Up to 12 months follow up

• Medical Outcomes Study Cognitive Functioning Scale (MOS-CF)

  The Medical Outcomes Study - Cognitive Functioning (MOS-CF) self-report scale consists of 6 items that are designed to measure perceived cognitive functioning. Each item is scored on a 6-point scale (1-6), with 1 being 'all of the time' and 6 being 'none of the time.' Higher scores indicate higher cognitive functioning and lower cognitive symptoms. Collected - Group 1: Baseline, pre-HRT, pre-MeRT, mid-MeRT (week 3 MeRT), pre-Ibo/5Meo, post-Ibo/5Meo, 3 month follow up (MFU), 6 MFU, 12 MFU; Group 2: Baseline, pre-HRT, pre-Ibo/5Meo, pre-MeRT, mid-MeRT, Post-MeRT, 3 MFU, 6 MFU, 12 MFU

  UP to 12 months follow up

• Externalized Free Recall with Emotional Words

  In the Externalized Free Recall with Emotional Words task, participants will be presented with a series of emotionally positive, negative, and neutral stimuli (e.g., words or images) and asked to recall the stimuli. The task captures how well individuals retain and recall emotional versus neutral content. Dependent variables include the total number of words recalled, total number of words recalled as a function of emotion, total number of recall intrusions, total number of prior-list intrusions as a function of emotion, overall monitoring accuracy percentage, and monitoring accuracy percentage, as a function of emotion. Collected - Group 1: Baseline, pre-HRT, pre-MeRT, mid-MeRT (week 3 MeRT), pre-Ibo/5Meo, post-Ibo/5Meo, 3 month follow up (MFU), 6 MFU, 12 MFU; Group 2: Baseline, pre-HRT, pre-Ibo/5Meo, pre-MeRT, mid-MeRT, Post-MeRT, 3 MFU, 6 MFU, 12 MFU

  Up to 12 months follow up

• Incidence of Adverse Events

  Adverse event monitoring at post-treatment and follow-up

  Up to 3-months follow-up

• Depressive Symptom Index-Suicidality Subscale (DSI-SS)

  Used to assess severity of suicide ideation. The measure consists of 4 items, each with a Likert-type scale (0-4) indicating the frequency and severity of different aspects of suicidal ideation (e.g., planfulness, control, impulse). Higher scores indicate greater levels of suicidal ideation. Collected - Group 1: Baseline, pre-HRT, pre-MeRT, mid-MeRT (week 3 MeRT), pre-Ibo/5Meo, post-Ibo/5Meo, 3 month follow up (MFU), 6 MFU, 12 MFU; Group 2: Baseline, pre-HRT, pre-Ibo/5Meo, pre-MeRT, mid-MeRT, Post-MeRT, 3 MFU, 6 MFU, 12 MFU

  Up to 12 months follow up

Study Arms (2)

Individuals in this arm will undergo HRT, then Ibogaine and 5-MeO treatment, and then MeRT therapy.

EXPERIMENTAL

Other: Hormone Replacement Therapy (HRT); Other: Magnetic Resonance Therapy (MeRT); Drug: ibogaine with magnesium treatment; Drug: 5-MeO-DMT

Individuals in this arm will undergo HRT, then MeRT therapy, and then Ibogaine and 5-MeO-DMT.

ACTIVE COMPARATOR

Other: Hormone Replacement Therapy (HRT); Other: Magnetic Resonance Therapy (MeRT); Drug: ibogaine with magnesium treatment; Drug: 5-MeO-DMT

Interventions

Hormone Replacement Therapy (HRT) OTHER

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.

Individuals in this arm will undergo HRT, then Ibogaine and 5-MeO treatment, and then MeRT therapy.; Individuals in this arm will undergo HRT, then MeRT therapy, and then Ibogaine and 5-MeO-DMT.

Magnetic Resonance Therapy (MeRT) OTHER

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.

Also known as: Transcranial Magnetic Stimulation

Individuals in this arm will undergo HRT, then Ibogaine and 5-MeO treatment, and then MeRT therapy.; Individuals in this arm will undergo HRT, then MeRT therapy, and then Ibogaine and 5-MeO-DMT.

ibogaine with magnesium treatment DRUG

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.

Individuals in this arm will undergo HRT, then Ibogaine and 5-MeO treatment, and then MeRT therapy.; Individuals in this arm will undergo HRT, then MeRT therapy, and then Ibogaine and 5-MeO-DMT.

5-MeO-DMT DRUG

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.

Individuals in this arm will undergo HRT, then Ibogaine and 5-MeO treatment, and then MeRT therapy.; Individuals in this arm will undergo HRT, then MeRT therapy, and then Ibogaine and 5-MeO-DMT.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• Special Operators Care Fund: collaborator

Study Sites (1)

Johns Hopkins Center for Psychedelic and Consciousness Research

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Combat Disorders; Cognitive Dysfunction; Brain Injuries, Traumatic; Brain Injuries; Stress Disorders, Post-Traumatic

Interventions

Hormone Replacement Therapy; Transcranial Magnetic Stimulation; Ibogaine; Methoxydimethyltryptamines

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics; Magnetic Field Therapy; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; N,N-Dimethyltryptamine; Tryptamines; Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Bufotenin; Serotonin

Study Officials

• Sandeep Nayak, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2025
• First Posted: February 6, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 22, 2025

Record last verified: 2025-08

Locations

US (1)