NRF for Traumatic Brain Injury

Recruiting at 1 trial location

Overseen By Annell Ovalles, MPH

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Icahn School of Medicine at Mount Sinai

Disqualifiers: Non-English speaking, Under 18

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: up to 36 months

765 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the effectiveness of NeuroResource Facilitation, a novel/innovative intervention, in reducing recidivism in offenders with brain injury (BI).

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment NeuroResource Facilitation (NRF) for Traumatic Brain Injury?

Research suggests that treatments promoting brain recovery, like NRF, may help after a traumatic brain injury by supporting brain cell growth and repair. Although NRF specifically isn't mentioned, similar strategies that encourage brain healing processes show promise in aiding recovery. ^{1 2 3 4 5}

How is the treatment NeuroResource Facilitation (NRF) unique for traumatic brain injury?

NeuroResource Facilitation (NRF) is unique because it focuses on enhancing the body's natural protective mechanisms by activating the Nrf2 pathway, which helps increase the expression of genes that protect against oxidative damage after a traumatic brain injury. This approach is different from other treatments that may not specifically target these endogenous protective pathways. ^{2 3 6 7 8}

Research Team

Maria Kajankova

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

This trial is for English-speaking adults over 18 with a history of brain injury, who are returning to specific counties in the U.S. within six months of release from incarceration. They must show significant cognitive impairment on certain tests.

Inclusion Criteria

Returning to 6 county area (Bucks, Chester, Delaware, Montgomery, Philadelphia and Schuylkill)

I am 18 years old or older.

Proficient in English

Exclusion Criteria

I am younger than 18 years old.

Non-English Speaking

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive specialized care management through NeuroResource Facilitation (NRF) both in prison and after release, with weekly to monthly meetings depending on resource needs.

up to 36 months

Weekly to monthly visits (in-person)

Follow-up

Participants are monitored for recidivism and engagement with health/medical resources, productive activities, and community support.

up to 36 months post release

Treatment Details

Interventions

• NeuroResource Facilitation (NRF)

Trial Overview The study is testing NeuroResource Facilitation (NRF), an innovative approach aimed at reducing repeat offenses among individuals with traumatic brain injuries by providing them with specialized support and resources.

Participant Groups

Group I: NeuroResource Facilitation Active Control 1 Intervention

As part of the NRF intervention group, participants will receive specialized care management, both in prison and after the participant goes home. While in the State Correctional Institution (SCI), participants will meet weekly to monthly depending on resource needs, and how close participant is to release with a NeuroResource Facilitator in person who will help participants to understand more about their challenges. Participants may also be referred to a group run by the Facilitator in conjunction with staff from the prison. The facilitator will also tell the participant about resources that are available to help after the participant's release and help participants get connected to them.

Group II: Standard of Care Active Control 1 Intervention

As part of the SoC, participants will receive the re-entry services normally receive if not in the study including (but not limited to) Treatment Services, Educational and Vocational Training, Mental Health Management, Reentry and Transitional Services, Population Management and Community Corrections.

NeuroResource Facilitation (NRF) is already approved in United States for the following indications:

Approved in United States as NeuroResource Facilitation for:

• Support for individuals with traumatic brain injuries

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Brain Injury Association of Pennsylvania

Collaborator

Trials

1

Recruited

770+

Findings from Research

Neuroprotective agents are being researched as potential treatments to prevent secondary brain injury after traumatic brain injuries, which could significantly improve patient outcomes.

If approved, critical care nurses will play a crucial role in administering these agents, monitoring side effects, and assessing their effectiveness in real-world clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental neuroprotective agents: nursing challenge. Hilton, G.[2019]

In a study of 210 participants (105 severe traumatic brain injury patients and 105 controls), higher serum levels of Nrf2 were significantly associated with greater traumatic severity and poorer prognosis, indicating its potential role as a biomarker for sTBI outcomes.

Patients with serum Nrf2 levels above the median had shorter overall survival times and higher mortality rates, suggesting that Nrf2 levels can predict 180-day mortality and poor outcomes when combined with clinical assessments like Glasgow Coma Scale and Rotterdam CT scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of serum nuclear factor erythroid 2-related factor 2 as a potential prognostic biomarker of severe traumatic brain injury in adults: A prospective cohort study. Yan, XJ., Zhan, CP., Lv, Y., et al.[2022]

The study found that the transcription factor Nrf2, which helps activate protective genes, shows increased expression in the cortex and hippocampus after traumatic brain injury (TBI), particularly at 48 hours and 1 week post-injury, indicating a delayed protective response.

Despite the activation of Nrf2-ARE-mediated protective genes, this response coincides with the onset of lipid peroxidative damage, highlighting the need for pharmacological agents that can enhance Nrf2 activation earlier after TBI to better protect against oxidative damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporal and spatial dynamics of nrf2-antioxidant response elements mediated gene targets in cortex and hippocampus after controlled cortical impact traumatic brain injury in mice. Miller, DM., Wang, JA., Buchanan, AK., et al.[2021]

A four-year-old boy with severe traumatic brain injury showed significant clinical improvements after receiving intranasal nerve growth factor (NGF) treatment, including better voluntary movements, facial expressions, and communication abilities.

NGF administration was safe, with no reported side effects, and resulted in increased levels of NGF and the neurogenesis marker Doublecortin (DCX) in the cerebrospinal fluid, suggesting a potential neuroprotective effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal Nerve Growth Factor administration improves cerebral functions in a child with severe traumatic brain injury: A case report. Chiaretti, A., Conti, G., Falsini, B., et al.[2022]

Traumatic brain injury (TBI) is a significant global health issue, affecting 1.5 million people annually in the U.S. alone, with a high economic burden and limited success in finding effective neuroprotective treatments in clinical trials.

Emerging research highlights the potential of neurorestorative strategies that enhance processes like angiogenesis, axonal remodeling, neurogenesis, and synaptogenesis, offering new avenues for repairing brain tissue and improving recovery after TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurorestorative treatments for traumatic brain injury. Xiong, Y., Mahmood, A., Chopp, M.[2022]

Mice lacking the Nrf2 gene were more vulnerable to acute intestinal mucosal injury after a traumatic brain injury (TBI), showing greater gut damage and higher levels of harmful substances in the blood.

Nrf2 appears to protect against TBI-induced intestinal injury by regulating inflammatory responses and promoting the activity of antioxidant and detoxifying enzymes, highlighting its potential role in recovery after brain injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcription factor Nrf2 plays a pivotal role in protection against traumatic brain injury-induced acute intestinal mucosal injury in mice. Jin, W., Wang, HD., Hu, ZG., et al.[2009]

The Nrf2/ARE pathway is activated after traumatic brain injury (TBI), leading to increased levels of Nrf2 protein, which helps protect nerve cells by inhibiting oxidative stress injuries.

In mice lacking the Nrf2 gene, there was no significant increase in protective proteins (HO-1 and NQO1) after TBI, indicating that the Nrf2 pathway is crucial for the body's response to oxidative stress following brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression and antioxidation of Nrf2/ARE pathway in traumatic brain injury. Cheng, ZG., Zhang, GD., Shi, PQ., et al.[2018]

Neuroprotection factors (NPFs) released from injured cells play a crucial role in protecting the brain from further damage after injuries, with various factors like neurotrophins and cytokines being identified as key players in this response.

Recent studies have found that low-molecular-weight compounds can mimic the effects of NPFs by activating important cellular signaling pathways, showing promise in animal models for treating traumatic brain injury (TBI) and suggesting potential new therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endogenous neuroprotection factors and traumatic brain injury: mechanisms of action and implications for therapy. Mattson, MP., Scheff, SW.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Experimental neuroprotective agents: nursing challenge. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Utility of serum nuclear factor erythroid 2-related factor 2 as a potential prognostic biomarker of severe traumatic brain injury in adults: A prospective cohort study. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Temporal and spatial dynamics of nrf2-antioxidant response elements mediated gene targets in cortex and hippocampus after controlled cortical impact traumatic brain injury in mice. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Intranasal Nerve Growth Factor administration improves cerebral functions in a child with severe traumatic brain injury: A case report. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Neurorestorative treatments for traumatic brain injury. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Transcription factor Nrf2 plays a pivotal role in protection against traumatic brain injury-induced acute intestinal mucosal injury in mice. [2009]

7. India pubmed.ncbi.nlm.nih.gov

Expression and antioxidation of Nrf2/ARE pathway in traumatic brain injury. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Endogenous neuroprotection factors and traumatic brain injury: mechanisms of action and implications for therapy. [2013]