The Use of Exosomes In Craniofacial Neuralgia

Neuralgia Clinical Trial

Official title:

The Use of Exosomes In Craniofacial Neuralgia

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04202783
• Other study ID #: ICSS-2019-019
• Status: Suspended
• Phase: N/A
• Start date: December 1, 2023
• Est. completion date: December 1, 2024

Study information

• Verified date: September 2022
• Source: Neurological Associates of West Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 100
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neuralgia

Intervention

Other:
• Exosomes
Focused ultrasound delivery of intravenously-infused exosomes

Locations

Country	Name	City	State
United States	Neurological Associates of West LA	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Neurological Associates of West Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (13)

Balbi C, Piccoli M, Barile L, Papait A, Armirotti A, Principi E, Reverberi D, Pascucci L, Becherini P, Varesio L, Mogni M, Coviello D, Bandiera T, Pozzobon M, Cancedda R, Bollini S. First Characterization of Human Amniotic Fluid Stem Cell Extracellular Vesicles as a Powerful Paracrine Tool Endowed with Regenerative Potential. Stem Cells Transl Med. 2017 May;6(5):1340-1355. doi: 10.1002/sctm.16-0297. Epub 2017 Mar 8. — View Citation

Bollini S, Gentili C, Tasso R, Cancedda R. The Regenerative Role of the Fetal and Adult Stem Cell Secretome. J Clin Med. 2013 Dec 17;2(4):302-27. doi: 10.3390/jcm2040302. Review. — View Citation

Cruccu G. Trigeminal Neuralgia. Continuum (Minneap Minn). 2017 Apr;23(2, Selected Topics in Outpatient Neurology):396-420. doi: 10.1212/CON.0000000000000451. Review. — View Citation

Harding C, Heuser J, Stahl P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol. 1983 Aug;97(2):329-39. — View Citation

Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem. 1987 Jul 5;262(19):9412-20. — View Citation

Maarbjerg S, Di Stefano G, Bendtsen L, Cruccu G. Trigeminal neuralgia - diagnosis and treatment. Cephalalgia. 2017 Jun;37(7):648-657. doi: 10.1177/0333102416687280. Epub 2017 Jan 11. Review. — View Citation

Marchetti M, Pinzi V, De Martin E, Ghielmetti F, Fariselli L. Radiosurgery for trigeminal neuralgia: the state of art. Neurol Sci. 2019 May;40(Suppl 1):153-157. doi: 10.1007/s10072-019-03814-6. Review. — View Citation

Mikula I. [Craniofacial neuralgias]. Acta Med Croatica. 2008 May;62(2):163-72. Review. Croatian. — View Citation

O'Neill F, Nurmikko T, Sommer C. Other facial neuralgias. Cephalalgia. 2017 Jun;37(7):658-669. doi: 10.1177/0333102417689995. Epub 2017 Jan 29. Review. — View Citation

Pan BT, Teng K, Wu C, Adam M, Johnstone RM. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J Cell Biol. 1985 Sep;101(3):942-8. — View Citation

Rose FC. Trigeminal neuralgia. Arch Neurol. 1999 Sep;56(9):1163-4. — View Citation

Spina A, Mortini P, Alemanno F, Houdayer E, Iannaccone S. Trigeminal Neuralgia: Toward a Multimodal Approach. World Neurosurg. 2017 Jul;103:220-230. doi: 10.1016/j.wneu.2017.03.126. Epub 2017 Apr 2. Review. — View Citation

Zhang B, Yeo RW, Tan KH, Lim SK. Focus on Extracellular Vesicles: Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles. Int J Mol Sci. 2016 Feb 6;17(2):174. doi: 10.3390/ijms17020174. Review. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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