Multiple Treatments for Brain Injury

Overseen By Sandeep M Nayak, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: SSRIs

Disqualifiers: Schizophrenia, Bipolar, Epilepsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores four treatments to assist veterans who have experienced combat deployments and now face brain injuries and mental health challenges. The treatments being tested include hormone replacement therapy, magnetic resonance brain stimulation, ibogaine (a psychoactive substance) with magnesium treatment, and 5-MeO-DMT (a psychedelic compound). Researchers aim to determine how these treatments might reduce PTSD symptoms and improve cognitive skills. Veterans of Special Operations Forces experiencing mental and cognitive issues after combat might be suitable candidates for this trial. As a Phase 2 trial, this research measures the effectiveness of the treatments in an initial, smaller group, offering veterans a chance to contribute to potentially groundbreaking therapies.

Will I have to stop taking my current medications?

The trial requires participants to stop taking selective serotonin reuptake inhibitor (SSRI) medications. If you are on SSRIs, you must be willing to taper off them to join the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments tested in this study have different safety profiles. Here is a breakdown:

1. **5-MeO-DMT**: Early research suggests that 5-MeO-DMT, a psychedelic substance, might aid brain injuries and mental health issues. However, more detailed safety information from human studies is still needed.

2. **Hormone Replacement Therapy (HRT)**: Studies indicate that estrogen, a component of HRT, may protect the brain. However, some research also links HRT to a higher risk of dementia in women. The FDA has removed some safety warnings, suggesting it might be safer than previously thought.

3. **Ibogaine with Magnesium**: Research shows that combining ibogaine with magnesium may lower the risk of heart problems that ibogaine alone can cause. This combination has shown positive effects in treating depression and anxiety, particularly in veterans.

4. **Magnetic Resonance Therapy (MeRT)**: MeRT, similar to transcranial magnetic stimulation, is generally well-tolerated in studies. Mild side effects like headaches and nausea are common but usually resolve after a few sessions.

Each treatment has its own safety considerations, and ongoing research continues to explore their full safety profiles. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for brain injury because they offer innovative approaches that differ from standard care options like physical rehabilitation and medication to manage symptoms. Unlike traditional treatments, 5-MeO-DMT and ibogaine, combined with magnesium, are psychedelic compounds that may promote neuroplasticity and brain healing, potentially accelerating recovery. Hormone Replacement Therapy (HRT) is being investigated for its role in repairing brain tissue by balancing hormones that can influence brain function. Magnetic Resonance Therapy (MeRT) is a non-invasive technique that targets brainwave patterns, aiming to restore normal brain function more directly and rapidly. These treatments offer hope for more effective and quicker recovery options for individuals with brain injuries.

What evidence suggests that this trial's treatments could be effective for brain injury?

This trial will evaluate multiple treatments for brain injury. Studies have shown that 5-MeO-DMT, a type of psychedelic, may help with brain injuries by reducing mental health symptoms. Hormone Replacement Therapy (HRT) might improve thinking and memory problems after brain injuries, with some evidence suggesting it can help memory and brain structure. Research on ibogaine, especially when combined with magnesium, indicates it can significantly reduce PTSD and depression symptoms in veterans. Magnetic Resonance Therapy (MeRT) has shown some success in improving PTSD symptoms and brain function through magnetic stimulation. Each of these treatments has demonstrated positive effects in different studies, suggesting they could benefit brain injuries and mental health challenges. Participants in this trial will receive different combinations of these treatments to assess their effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

Sandeep Nayak, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for Special Operations Forces veterans aged 18 or older with a history of combat deployments and brain injuries, who are experiencing mental health and cognitive issues. It's not open to those with severe psychiatric disorders, major organ dysfunction, recent surgeries, abnormal blood tests, or unwillingness to stop taking SSRI medications.

Inclusion Criteria

Sponsored by SOC-F Program

Exclusion Criteria

I refuse to stop taking my SSRI medication.

Prolonged corrected QT interval (QTc) Interval (450ms in males; 470ms in females)

I have a major lung condition like emphysema or cystic fibrosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a sequence of treatments including Hormone Replacement Therapy, Magnetic e-Resonance Therapy, Ibogaine, and 5-MeO-DMT

12 weeks

Multiple visits for each treatment phase

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

3-month, 6-month, and 12-month follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• 5-MeO-DMT
• Hormone Replacement Therapy (HRT)
• ibogaine with magnesium treatment
• Magnetic Resonance Therapy (MeRT)

Trial Overview The Trifecta Research Study is testing the effects of hormone replacement therapy (HRT), magnetic resonance therapy (MeRT), ibogaine with magnesium treatment, and 5-MeO-DMT on veterans' PTSD symptoms and cognitive function. Johns Hopkins will observe outcomes without altering participants' normal routines.

How Is the Trial Designed?

Group I: Individuals in this arm will undergo HRT, then Ibogaine and 5-MeO treatment, and then MeRT therapy. Experimental Treatment 4 Interventions

Group II: Individuals in this arm will undergo HRT, then MeRT therapy, and then Ibogaine and 5-MeO-DMT. Active Control 4 Interventions

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Special Operators Care Fund

Collaborator

Trials

1

Recruited

40+

Published Research Related to This Trial

The psychedelic drug 5-MeO-DMT (GH001) was well tolerated in a study of 16 adults with treatment-resistant depression (TRD), showing significant safety in its administration.

In the Phase 2 trial, an individualized dosing regimen led to an impressive 87.5% remission rate by day 7, demonstrating potent and ultra-rapid antidepressant effects compared to lower remission rates in the single-dose groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression. Reckweg, JT., van Leeuwen, CJ., Henquet, C., et al.[2023]

In a survey of 362 participants who used 5-MeO-DMT in a structured group setting, 80% of those with depression and 79% with anxiety reported improvements in their conditions after use, suggesting potential therapeutic effects.

The improvements in depression and anxiety were linked to the intensity of mystical experiences and the perceived spiritual significance of the 5-MeO-DMT experience, rather than the challenging effects during the experience, indicating a unique mechanism of action that warrants further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. Davis, AK., So, S., Lancelotta, R., et al.[2020]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0278584625002027

Examining the potential of psilocybin and 5-MeO-DMT as ... Emerging evidence suggests that serotonergic psychedelics psilocybin and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) may hold promise as treatments for TBI.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40669813/

Examining the potential of psilocybin and 5-MeO-DMT as ... Emerging evidence suggests that serotonergic psychedelics psilocybin and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) may hold promise as treatments for TBI.

3. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.685085/full

Psychedelics for Brain Injury: A Mini-Review DMT has been shown to reduce ischemic brain injury after middle cerebral artery occlusion (MCAO) through S1R dependent activity in murine models ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/00952990.2023.2220874

Open-label study of consecutive ibogaine and 5-MeO-DMT ... Data suggest combined ibogaine and 5-MeO-DMT assisted therapy has potential to provide rapid and robust changes in mental health functioning.

5. nature.com nature.com/articles/s41598-024-53363-y

Effects of DMT on mental health outcomes in healthy ... Within a very small sample (n = 6), one recent study found significant decreases in depression 1 day after DMT administration28.

6. jheor.org jheor.org/post/2542-from-toad-toxin-to-medicine-the-promise-of-5-meo-dmt

From Toad Toxin to Medicine: The Promise of 5-MeO-DMT Scientists are working to study and develop synthetic formulations of 5-MeO-DMT for hard-to-treat mental health disorders, including depression, anxiety, and ...

7. biologicalpsychiatryjournal.com biologicalpsychiatryjournal.com/article/S0006-3223(23)00419-5/pdf

105. Intranasal 5-MeO-DMT: Safety, PK and Effect on ... Study, we examined 206 11-12-year-old children who experi- enced a concussion within two years after baseline data collection. Behavioral problems were assessed ...