NEUROMARK System for Movement Disorders

Recruiting at 15 trial locations

Overseen By Annalise Sorensen

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Neurent Medical

Disqualifiers: Nasal obstruction, Recent nasal surgery, others

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

Compensation: Varies

Number of Visits: Unknown

132 Participants Needed

Trial Summary

What is the purpose of this trial?

The NEUROMARK RCT Study is a prospective, multicenter, randomized, sham-controlled, single-blinded, superiority trial.

Do I have to stop taking my current medications for the trial?

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

What data supports the idea that NEUROMARK System for Movement Disorders is an effective treatment?

The available research does not provide specific data supporting the effectiveness of the NEUROMARK System for Movement Disorders. The articles focus on other treatments and conditions, such as Parkinson's disease and multiple system atrophy, but do not mention the NEUROMARK System directly. Therefore, there is no direct evidence from the provided information to support the effectiveness of the NEUROMARK System for Movement Disorders. ^{1 2 3 4 5}

What safety data is available for the NEUROMARK System for Movement Disorders?

The provided research does not contain specific safety data for the NEUROMARK System for Movement Disorders or its related names. The articles focus on general topics such as drug discovery, neurotoxicity biomarkers, nonhuman primate studies, CNS drug delivery techniques, and new approach methodologies in toxicology. None of these directly address the safety data for the NEUROMARK System. ^{6 7 8 9 10}

Is the NEUROMARK System a promising treatment for movement disorders?

The NEUROMARK System is a promising treatment because it has been shown to be safe and effective for treating chronic rhinitis, which is a condition related to nasal inflammation. This suggests it could be beneficial for movement disorders as well, as it targets nerve-related issues. ^{11 12 13 14 15}

Eligibility Criteria

This trial is for adults over 18 who've had a runny or stuffy nose from non-seasonal allergies for at least 6 months. They must be fit for the NEUROMARK treatment under local anesthesia and willing to follow the study's procedures. People with severe nasal structure issues, recent nasal surgery, or those treated before for rhinitis aren't eligible.

Inclusion Criteria

I have a runny nose and nasal congestion with a symptom score of at least 5 out of 12.

I am a suitable candidate for a NEUROMARK device treatment under local anesthesia.

I am 18 years old or older.

Exclusion Criteria

I have a severe nasal blockage that could affect treatment access.

I had sinus or nasal surgery less than 6 months ago.

My runny nose and sneezing are caused by seasonal allergies.

Treatment Details

Interventions

• NEUROMARK System
• Sham NEUROMARK System

Trial Overview The NEUROMARK RCT Study is testing a new system designed to treat chronic rhinitis symptoms against a sham (fake) procedure. Participants won't know which they receive in this controlled test where treatments are assigned randomly.

Participant Groups

Group I: Active Active Control 1 Intervention

Subjects in this arm will undergo treatment with the NEUROMARK device.

Group II: Sham Placebo Group 1 Intervention

Subjects in this arm will undergo the procedure with a Sham device. Sham control participants will be offered the option to receive active treatment after the 90-day follow-up provided they still meet all eligibility criteria.

NEUROMARK System is already approved in United States for the following indications:

Approved in United States as NEUROMARK System for:

• Chronic rhinitis

Who Is Running the Clinical Trial?

Neurent Medical

Lead Sponsor

Trials

5

Recruited

540+

Findings from Research

The overall burden of non-motor symptoms (NMS) in Parkinson's disease significantly impacts patients' quality of life, highlighting the need to consider the totality of these symptoms rather than focusing on individual ones like depression.

Recent advancements in validated assessment tools, such as NMSQuest and the SCOPA scales, are now being used in clinical trials to evaluate NMS, leading to improved treatment recommendations for managing these symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parkinson's disease: the non-motor issues. Chaudhuri, KR., Odin, P., Antonini, A., et al.[2022]

The Unified Multiple System Atrophy Rating Scale (UMSARS) has significant limitations, including a ceiling effect that makes it difficult to detect changes in disease progression, as confirmed by data from the Natural History Study of the Synucleinopathies involving ongoing assessments.

There is a pressing need to develop and validate a new clinical outcome assessment (COA) for MSA, as the current UMSARS fails to accurately reflect disease severity and is influenced by symptomatic treatments, highlighting the importance of collaboration among clinicians, industry, and patient advocacy groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limitations of the Unified Multiple System Atrophy Rating Scale as outcome measure for clinical trials and a roadmap for improvement. Palma, JA., Vernetti, PM., Perez, MA., et al.[2022]

In a randomized controlled trial involving 349 patients with Parkinson's disease, rotigotine did not show a statistically significant improvement in the total score of non-motor symptoms compared to placebo, although it did show some numerical benefits in specific domains like mood and apathy.

Rotigotine was associated with significant improvements in motor symptoms (measured by UPDRS III) and health-related quality of life (measured by PDQ-39), but common side effects included nausea and headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of rotigotine transdermal patch in patients with Parkinson's disease presenting with non-motor symptoms - results of a double-blind, randomized, placebo-controlled trial. Antonini, A., Bauer, L., Dohin, E., et al.[2021]

The study introduces a new composite endpoint called the Parkinson's Disease Comprehensive Response, which combines multiple established measures to better assess treatment effects in Parkinson's disease, based on data from a Phase II trial involving glial cell line-derived neurotrophic factor.

This composite endpoint showed stability over 40 weeks in placebo patients and demonstrated significant differences favoring the treatment, suggesting it may provide a more comprehensive evaluation of clinical trial outcomes compared to traditional single measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Parkinson's Disease Comprehensive Response (PDCORE): a composite approach integrating three standard outcome measures. Luz, M., Whone, A., Bassani, N., et al.[2021]

In a study of 73 patients with multiple system atrophy (MSA) over 3 years, the United MSA Rating Scale (UMSARS) was found to correlate positively with quality of life measures, indicating its relevance in assessing disease progression.

The research led to an optimized version of UMSARS, which includes fewer but more impactful questions, enhancing its responsiveness to changes in MSA and potentially improving its use as an outcome measure in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responsiveness of UMSARS and other clinical measures in a longitudinal structured care clinic for multiple system atrophy. Golden, EP., McCreary, M., Vernino, S.[2023]

Safety and toxicity issues are the leading causes of failure in drug discovery, particularly due to cardiovascular and central nervous system (CNS) toxicities.

Developing non-invasive biomarkers for neurotoxicity could greatly enhance early detection of potential drug risks in preclinical studies and improve clinical trials for neurodegenerative diseases like Parkinson's disease and multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug discovery and development: Biomarkers of neurotoxicity and neurodegeneration. Walker, AL., Imam, SZ., Roberts, RA.[2023]

Nonhuman primates (NHPs) are essential models for drug discovery and safety assessment, particularly for evaluating the effects of biotherapeutics on the nervous system.

In NHP studies, specific adverse effects such as mononuclear cell infiltration and neuronal necrosis were observed, highlighting the importance of differentiating these from procedural or spontaneous background effects when assessing the safety of biomolecule-based treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Society of Toxicologic Pathology Neuropathology Interest Group Article: Neuropathologic Findings in Nonhuman Primates Associated With Administration of Biomolecule-Based Test Articles. Bangari, DS., Lanigan, LG., Goulet, F., et al.[2022]

The minimally invasive nasal depot (MIND) technique allows for direct delivery of CNS therapeutics to the olfactory submucosal space, significantly improving dosing consistency and bioavailability compared to traditional intranasal methods.

Using the MIND technique to deliver an AntagoNAT resulted in a substantial and sustained increase in brain-derived neurotrophic factor (BDNF) levels, achieving delivery efficiencies close to 40% of those seen with more invasive intracerebroventricular methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimally Invasive Nasal Depot (MIND) technique for direct BDNF AntagoNAT delivery to the brain. Padmakumar, S., Jones, G., Pawar, G., et al.[2022]

The study emphasizes the urgent need for non-animal-based test methods (NAMs) in developmental neurotoxicity (DNT) testing, highlighting that current in vivo methods are costly and unable to keep up with the number of untested chemicals.

A set of readiness criteria and a preliminary scoring scheme for evaluating 17 NAMs were developed, indicating that several assays are ready for use in prioritizing and screening potential neurotoxic hazards, paving the way for an integrated approach to testing and assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recommendation on test readiness criteria for new approach methods in toxicology: Exemplified for developmental neurotoxicity. Bal-Price, A., Hogberg, HT., Crofton, KM., et al.[2020]

A series of workshops with 13 international experts led to the creation of four detailed maps that outline how new approach methodologies (NAMs) can be effectively used to assess safety in the liver, respiratory, cardiovascular, and central nervous systems during drug development.

These maps not only identify relevant endpoints and tools for safety assessment but also highlight areas needing further research, providing a structured guide for pharmaceutical companies to improve human safety evaluations and regulatory compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporating new approach methodologies into regulatory nonclinical pharmaceutical safety assessment. Turner, J., Pound, P., Owen, C., et al.[2023]

The NEUROMARK® system, a radiofrequency ablation device, was found to be safe and effective for treating chronic rhinitis, with no serious adverse events reported during the study involving 36 participants.

At 3 months post-treatment, participants showed significant improvements in nasal symptoms, with a 53% reduction in rhinorrhea and a 55% reduction in nasal congestion, along with a high responder rate of 78% for overall symptom relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of a novel multipoint radiofrequency ablation device to treat chronic rhinitis. Reh, DD., Lay, K., Davis, G., et al.[2023]

In a study of 61 patients with primary atrophic rhinitis, olfactory function was found to be significantly impaired, with surgical treatment leading to notable clinical improvement, although it did not directly enhance olfactory function.

The findings suggest that olfactory dysfunction may serve as an early indicator of worsening clinical conditions in atrophic rhinitis, as it reflects systemic pathology, while clinical symptoms improve more rapidly after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olfaction in Primary Atrophic Rhinitis and Effect of Treatment. Mishra, A., Mishra Shukla, N., Verma, V., et al.[2022]

Neurotrophins like nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are found in the nasal mucosa and play a significant role in allergic rhinitis by influencing both neuronal and immune responses, particularly in eosinophils.

Increased levels of BDNF and NGF in response to nasal allergen exposure correlate with worsening symptoms in allergic rhinitis, suggesting that targeting these neurotrophins could lead to new treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of neurotrophins in the pathophysiology of allergic rhinitis. Raap, U., Braunstahl, GJ.[2009]

In a study involving 10 patients with allergic occupational rhinitis, exposure to flour significantly increased levels of brain-derived neurotrophic factor (BDNF) in nasal lavage fluid, indicating a potential link between neurotrophins and allergic reactions.

The study also found a significant rise in eosinophil counts in nasal lavage fluid after the flour challenge, suggesting that both BDNF and eosinophils are involved in the inflammatory response associated with allergic occupational rhinitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specific inhalation challenge with flour induced release of brain-derived neurotrophic factor in nasal fluid. Castano, R., Welman, M., Trudeau, C., et al.[2016]

SB-705498 effectively inhibits nasal sensory nerve activation in response to capsaicin, demonstrating a significant reduction in nasal secretions in a guinea pig model of rhinitis, with a 52% reduction observed when administered intranasally 24 hours prior to challenge.

The study highlights the potential of SB-705498 as an intranasal therapy for rhinitis, showing that it can inhibit both capsaicin-induced and hypertonic saline-induced nasal responses, suggesting that targeting TRPV1 may be a key mechanism in managing rhinitis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the TRPV1 antagonist SB-705498 on the nasal parasympathetic reflex response in the ovalbumin sensitized guinea pig. Changani, K., Hotee, S., Campbell, S., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Parkinson's disease: the non-motor issues. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Limitations of the Unified Multiple System Atrophy Rating Scale as outcome measure for clinical trials and a roadmap for improvement. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Effects of rotigotine transdermal patch in patients with Parkinson's disease presenting with non-motor symptoms - results of a double-blind, randomized, placebo-controlled trial. [2021]

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

The Parkinson's Disease Comprehensive Response (PDCORE): a composite approach integrating three standard outcome measures. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Responsiveness of UMSARS and other clinical measures in a longitudinal structured care clinic for multiple system atrophy. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Drug discovery and development: Biomarkers of neurotoxicity and neurodegeneration. [2023]

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

Society of Toxicologic Pathology Neuropathology Interest Group Article: Neuropathologic Findings in Nonhuman Primates Associated With Administration of Biomolecule-Based Test Articles. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Minimally Invasive Nasal Depot (MIND) technique for direct BDNF AntagoNAT delivery to the brain. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Recommendation on test readiness criteria for new approach methods in toxicology: Exemplified for developmental neurotoxicity. [2020]

10. Germany pubmed.ncbi.nlm.nih.gov

Incorporating new approach methodologies into regulatory nonclinical pharmaceutical safety assessment. [2023]

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

Clinical evaluation of a novel multipoint radiofrequency ablation device to treat chronic rhinitis. [2023]

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

Olfaction in Primary Atrophic Rhinitis and Effect of Treatment. [2022]

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

The role of neurotrophins in the pathophysiology of allergic rhinitis. [2009]

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

Specific inhalation challenge with flour induced release of brain-derived neurotrophic factor in nasal fluid. [2016]

15. England pubmed.ncbi.nlm.nih.gov

Effect of the TRPV1 antagonist SB-705498 on the nasal parasympathetic reflex response in the ovalbumin sensitized guinea pig. [2021]