NE3107 for Traumatic Brain Injury
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Neurological Associates of West Los Angeles
Must not be taking: Sleep aids
Disqualifiers: Neurological, Psychiatric, Substance abuse, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This study seeks to measure changes in cognition through verbal and visual test procedures and changes in biomarkers of Traumatic Brain Injury and inflammatory and metabolic parameters.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
How is the drug NE3107 different from other treatments for traumatic brain injury?
Eligibility Criteria
This trial is for adults aged 18-75 with traumatic brain injury confirmed by a medical professional. Participants must experience significant fatigue or sleepiness, as indicated by specific scores on the MFI and ESS or PSI scales. They need to be able to consent themselves or have someone who can consent for them, and commit to the study duration.Inclusion Criteria
I am between 18 and 75 years old.
Multidimensional Fatigue Inventory (MFI) score of 27 or greater
I can commit to the full length of the study.
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Exclusion Criteria
I am not willing to use two forms of birth control.
My liver function tests are high, or I have a significant liver disease.
Significant language impairment with expressive or receptive aphasia
See 12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive 200mg BID of NE3107 for 6 months to evaluate its effects on sleep and fatigue in TBI subjects
6 months
Visits at Baseline, 3 months, and 6 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- NE3107 (Insulin Sensitizer)
Trial OverviewThe trial is testing NE3107, focusing on its effects on improving cognition through verbal and visual tests, as well as assessing changes in biomarkers related to traumatic brain injury and various inflammatory and metabolic parameters.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Experimental Arm: NE3107Experimental Treatment1 Intervention
All participants will take 200mg BID (12 hours apart) of NE3107 for 6 months.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The Regenesis ProjectSanta Monica, CA
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Who Is Running the Clinical Trial?
Neurological Associates of West Los AngelesLead Sponsor
BioVie Inc.Industry Sponsor
References
JM-20 Treatment After Mild Traumatic Brain Injury Reduces Glial Cell Pro-inflammatory Signaling and Behavioral and Cognitive Deficits by Increasing Neurotrophin Expression. [2022]Traumatic brain injury (TBI) is considered a public health problem and is often related to motor and cognitive disabilities, besides behavioral and emotional changes that may remain for the rest of the subject's life. Resident astrocytes and microglia are the first cell types to start the inflammatory cascades following TBI. It is widely known that continuous or excessive neuroinflammation may trigger many neuropathologies. Despite the large numbers of TBI cases, there is no effective pharmacological treatment available. This study aimed to investigate the effects of the new hybrid molecule 3-ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-4,11-dihydro1H-pyrido[2,3-b][1,5]benzodiazepine (JM-20) on TBI outcomes. Male Wistar rats were submitted to a weight drop model of mild TBI and treated with a single dose of JM-20 (8 mg/kg). Twenty-four hours after TBI, JM-20-treated animals showed improvements on locomotor and exploratory activities, and short-term memory deficits induced by TBI improved as well. Brain edema was present in TBI animals and the JM-20 treatment was able to prevent this change. JM-20 was also able to attenuate neuroinflammation cascades by preventing glial cells-microglia and astrocytes-from exacerbated activation, consequently reducing pro-inflammatory cytokine levels (TNF-α and IL-1β). BDNF mRNA level was decreased 24 h after TBI because of neuroinflammation cascades; however, JM-20 restored the levels. JM-20 also increased GDNF and NGF levels. These results support the JM-20 neuroprotective role to treat mild TBI by reducing the initial damage and limiting long-term secondary degeneration after TBI.
Mechanism of action for NNZ-2566 anti-inflammatory effects following PBBI involves upregulation of immunomodulator ATF3. [2021]The tripeptide glycine-proline-glutamate analogue NNZ-2566 (Neuren Pharmaceuticals) demonstrates neuroprotective efficacy in models of traumatic brain injury. In penetrating ballistic-like brain injury (PBBI), it significantly decreases injury-induced upregulation of inflammatory cytokines including TNF-α, IFN-γ, and IL-6. However, the mechanism by which NNZ-2566 acts has yet to be determined. The activating transcription factor-3 (ATF3) is known to repress expression of these inflammatory cytokines and was increased at the mRNA and protein level 24-h post-PBBI. This study investigated whether 12 h of NNZ-2566 treatment following PBBI alters atf3 expression. PBBI alone significantly increased atf3 mRNA levels by 13-fold at 12 h and these levels were increased by an additional fourfold with NNZ-2566 treatment. To confirm that changes in mRNA translated to changes in protein expression, ATF3 expression levels were determined in vivo in microglia/macrophages, T cells, natural killer cells (NKCs), astrocytes, and neurons. PBBI alone significantly increased ATF3 in microglia/macrophages (820%), NKCs (58%), and astrocytes (51%), but decreased levels in T cells (48%). NNZ-2566 treatment further increased ATF3 protein expression in microglia/macrophages (102%), NKCs (308%), and astrocytes (13%), while reversing ATF3 decreases in T cells. Finally, PBBI increased ATF3 levels by 55% in neurons and NNZ-2566 treatment further increased these levels an additional 33%. Since increased ATF3 may be an innate protective mechanism to limit inflammation following injury, these results demonstrating that the anti-inflammatory and neuroprotective drug NNZ-2566 increase both mRNA and protein levels of ATF3 in multiple cell types provide a cellular mechanism for NNZ-2566 modulation of neuroinflammation following PBBI.
Neuroprotection by memantine, a non-competitive NMDA receptor antagonist after traumatic brain injury in rats. [2019]This study investigated whether memantine, a non-competitive NMDA receptor antagonist is neuroprotective after traumatic brain injury (TBI) induced in adult rats with a controlled cortical impact device. TBI led to significant neuronal death in the hippocampal CA2 and CA3 regions (by 50 and 59%, respectively), by 7 days after the injury. Treatment of rats with memantine (10 and 20 mg/Kg, i.p.) immediately after the injury significantly prevented the neuronal loss in both CA2 and CA3 regions. This is the first study showing the neuroprotective potential of memantine to prevent the TBI-induced neuronal damage.
NNZ-2566 treatment inhibits neuroinflammation and pro-inflammatory cytokine expression induced by experimental penetrating ballistic-like brain injury in rats. [2021]Inflammatory cytokines play a crucial role in the pathophysiology of traumatic brain injury (TBI), exerting either deleterious effects on the progression of tissue damage or beneficial roles during recovery and repair. NNZ-2566, a synthetic analogue of the neuroprotective tripeptide Glypromate, has been shown to be neuroprotective in animal models of brain injury. The goal of this study was to determine the effects of NNZ-2566 on inflammatory cytokine expression and neuroinflammation induced by penetrating ballistic-like brain injury (PBBI) in rats.
A 5-HT6R agonist alleviates cognitive dysfunction after traumatic brain injury in rats by increasing BDNF expression. [2022]Effective treatment for cognitive dysfunction after traumatic brain injury (TBI) is lacking in clinical practice. Increased brain-derived neurotrophic factor (BDNF) expression in cognitive circuits can significantly alleviate cognitive dysfunction in animal models of TBI. Selective 5-hydroxytryptamine receptor 6 (5-HT6R) agonists significantly increase BDNF expression and improve cognitive function. Therefore, we evaluated the protective effect of a highly selective 5-HT6R agonist, WAY-181187, on cognitive dysfunction after TBI. We established a controlled cortical impact model of moderate TBI in rats and performed drug intervention for five consecutive days. Rats had spatial reference memory impairment in the Morris water maze one and four weeks after TBI. BDNF expression in the medial prefrontal cortex (mPFC) and hippocampus decreased two and five weeks after TBI. Additionally, five weeks after TBI, decreases in neuronal dendritic spine density and the proportion of thin, mushroom-shaped dendritic spines and an increased proportion of stubby-type dendritic spines were observed. WAY-181187 administration (3 mg/kg) for five consecutive days after TBI significantly alleviated cognitive dysfunction at one and four weeks (P < 0.001 and P < 0.01), upregulated BDNF expression in the mPFC and hippocampus at two (P < 0.01 and P < 0.05) and five (P < 0.01 and P < 0.001) weeks and increased the dendritic spine density and the proportions of thin, mushroom-shaped dendrites in the mPFC (P < 0.05, P < 0.001 and P < 0.01) and hippocampus (P < 0.05, P < 0.001 and P < 0.05) at five weeks after TBI. Our results confirm that WAY-181187 administration (3 mg/kg) in the acute phase alleviated cognitive dysfunction after TBI, possibly by upregulating BDNF expression in the mPFC and hippocampus, enhancing neuroplasticity.