The Use of Exosomes In Craniofacial Neuralgia

Study Overview
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Brief Summary
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This study is designed to evaluate the safety and efficacy of exosome deployment in patients with Craniofacial Neuralgia. Secondarily, this study is designed to rigorously evaluate for any adverse events that may be related to the administration and reception of exosomes.

Detailed Description
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The present study is designed to amplify the delivery of growth factors and anti-inflammatory agents to localized targets (determined by specific condition) by using focused transcranial ultrasound prior to intravenous infusion of exosomes. Exosomes delivered intravenously can be demonstrated to cross the blood brain barrier naturally. Exosomes are thought to play a normal physiological role in intercellular signaling, and demonstrate anti-inflammatory and pro-growth effects in preclinical models and clinical cases reports. Clinical trials have deployed exosomes intravenously and with intracerebral and intrathecal injection, and have claimed safety and clinical efficacy. Focused ultrasound has been shown to enhance local blood flow and has been presented as a non-invasive means of targeting delivery of therapeutic agents.

Official Title
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The Use of Exosomes In Craniofacial Neuralgia

Conditions
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Neuralgia

Intervention / Treatment
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* Other: Exosomes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female at least 18 years of age Clinical diagnosis of craniofacial neuralgia Exclusion Criteria: Subjects unable to give informed consent Subjects who would not be able to lay down without excessive movement in a calm environment sufficiently long enough to be able to achieve sleep Recent surgery or dental work within 3 months of the scheduled procedure. Pregnancy, women who may become pregnant or are breastfeeding Advanced terminal illness Any active cancer or chemotherapy Bone marrow disorder Myeloproliferative disorder Sickle cell disease Primary pulmonary hypertension Immunocompromising conditions and/or immunosuppressive therapies Macular degeneration Subjects with scalp rash or open wounds on the scalp (for example from treatment of squamous cell cancer) Advanced kidney, pulmonary, cardiac or liver failure Subjects with vascular causes of dementia Bleeding disorder, untreated

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: The present study is being undertaken as an open label study to evaluate the safety and feasibility of exosomes as an intervention for patients with craniofacial neuralgia. Baseline and outcome measures in this study utilize validated tests that are appropriate for repeated measures. The present study can be easily implemented because the neuropsychological testing instruments have been in routine clinical deployment providing for a high degree of availability and reliability. Quality assurance is tightly controlled. The study population is sufficiently broad and the conditions of interest are sufficiently prevalent so that recruitment of subjects is not a limiting factor.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment of Craniofacial Neuralgia<br>All patients will receive the same amount (5mL concentrated) of exosomes delivered via ultrasound-guided, regional epineural injection and the same amount (5mL unconcentrated) delivered via IV. Patients will be given 3 mL of the exosome product intravenously, which contains about 45mg of the exosome product containing 15-21 million neonatal stem cell products, and 3 mL of the exosome hyperconcentrate product delivered epineurally using ultrasound guidance, which contains about 15mg of the exosome product carrying 5-7 million neonatal stem cell products. | Other: Exosomes<br>* Focused ultrasound delivery of intravenously-infused exosomes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Pain Inventory (BPI) | The BPI is a 9 item self-report questionnaire used to evaluate the severity of a patient's pain and the impact of this pain on the patient's daily functioning. Self-report measure containing a composite pain score and functional interference score. The pain subscale contains 4 questions, each with answers ranging from 0 'no pain' to 10 'pain as bad as you can imagine.' Total possible score for the pain subscale is 40 points. The functional/interference subscale contains 7 questions, with each answer ranging from 0 'does not interfere' to 10 'completely interferes.' The maximum possible score for the interference subscale is 70 points. The total overall composite BPI score is out of 100 maximum points. A clinical improvement is considered a decrease in BPI overall composite score by at least 30% from baseline. | 8 weeks from baseline | 
| Patient Health Questionnaire (PHQ-9) | The Patient Health Questionnaire (PHQ) is a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders. The PHQ-9 is the depression module, which scores each of the 9 DSM-IV criteria as 0 (not at all) to 3 (nearly every day). Total possible score is 27 points. A clinical improvement is considered a decrease in BPI overall composite score by at least 30% from baseline. | 8 weeks from baseline | 
| Adverse Event Reporting | Adverse events (AEs) and any other untoward signs or symptoms were collected at each study timepoint starting at the treatment injection. Serious adverse events (SAEs) determined by the investigator to be related to the study treatment were formally recorded. | Baseline to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Rating of Change (GRC) | The GRC is a self-administered one-item Likert scale questionnaire on the patient's overall satisfaction with the treatment; with scores from -5 (very much worse) to +5 (very much better). A GRC of at least is considered to be clinically significant improvement. | 8 weeks from baseline | 
| Brief Pain Inventory (BPI) | The BPI is a 9 item self-report questionnaire used to evaluate the severity of a patient's pain and the impact of this pain on the patient's daily functioning. Self-report measure containing a composite pain score and functional interference score. The pain subscale contains 4 questions, each with answers ranging from 0 'no pain' to 10 'pain as bad as you can imagine.' Total possible score for the pain subscale is 40 points. The functional/interference subscale contains 7 questions, with each answer ranging from 0 'does not interfere' to 10 'completely interferes.' The maximum possible score for the interference subscale is 70 points. The total overall composite BPI score is out of 100 maximum points. A clinical improvement is considered a decrease in BPI overall composite score by at least 30% from baseline. | 24 weeks from baseline | 
| Patient Health Questionnaire (PHQ-9) | The Patient Health Questionnaire (PHQ) is a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders. The PHQ-9 is the depression module, which scores each of the 9 DSM-IV criteria as 0 (not at all) to 3 (nearly every day). Total possible score is 27 points. A clinical improvement is considered a decrease in BPI overall composite score by at least 30% from baseline. | 24 weeks from baseline |