Focused Ultrasound and Exosomes to Treat Depression, Anxiety, and Dementias

NCT ID: NCT04202770

Last Updated: 2022-09-28

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: NA
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-01
• Study Completion Date: 2024-12-31

Brief Summary

This study is designed to evaluate the safety and efficacy of exosome deployment with concurrent transcranial ultrasound in patients with refractory, treatment resistant depression, anxiety, and neurodegenerative dementia.

Detailed Description

The present study is designed to enhance 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, which are ubiquitous in blood, body fluids, and tissues are thought to play a normal physiological role in intercellular signaling. Exosomes delivered intravenously can be demonstrated to cross the blood brain barrier naturally. Exosomes and mesenchymal signaling cells (MSC's) demonstrate anti-inflammatory and pro-growth effects in preclinical models and clinical cases reports and have been used intravenously and with intracerebral and intrathecal injection. Various clinical trials have claimed safety and clinical efficacy.

Focused ultrasound has been demonstrated to enhance local blood flow and has been proposed as a non-invasive means of targeting delivery of therapeutic agents. The present paper was designed to use focused ultrasound as a means of enhancing delivery of intravenous exosomes to the subgenual target for patients with refractory depression, the amygdala for patients with anxiety, and the hippocampus for patients with cognitive impairment due to neurodegenerative disease.

Conditions

Refractory Depression; Anxiety Disorders; Neurodegenerative Diseases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Patients deemed potentially appropriate candidates for exosome and focused ultrasound therapy for either treatment refractory depression (trMDD), anxiety, or neurodegenerative dementia will be treated with exosomes derived from healthy, full-term Cesarean section amniotic fluid. Up to one hour of transcranial focused ultrasound will be administered immediately prior to exosome treatment in an attempt to facilitate enhanced deployment to the subgenual cingulate for trMDD, the amygdala for anxiety, or the hippocampus for dementia. Target location will be determined by the physician upon enrollment depending on the patient's specific syndrome. Patients will be given 15cc of unconcentrated solution allogenic exosomes (equivalent to 21 million stem cells, Kimera Corporation) intravenously in 200 ccs of normal saline dripped over thirty minutes to one hour.

Group Type: EXPERIMENTAL

Exosomes

Intervention Type: OTHER

Focused ultrasound delivery of intravenously-infused exosomes

Interventions

Exosomes

Focused ultrasound delivery of intravenously-infused exosomes

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

In order for a subject to be considered for the depression application of this study, the following criteria are required:

• Diagnosis of Major Depressive Disorder
• Score greater than 13 on the Beck Depression Inventory
• Failure to remit with 3 antidepressants
• At least 18 years of age

In order for a subject to be considered for the anxiety application of this study, the following criteria are required:

• Diagnosis of Generalized or Acute Anxiety Disorder
• Score greater than 22 on the Beck Anxiety Inventory
• Failure to remit with 3 anxiolytics
• At least 18 years of age

In order for a subject to be considered for the neurodegenerative application of this study, the following criteria are required:

• Cognitive decline with mild cognitive impairment (Clinical Dementia Rating stage 0.5) through moderate dementia (CDR stage 2)
• Lumbar puncture for Abeta 42 and Tau proteins evincing clinical correlation of neurodegenerative disease pathology
• Advanced MRI of the brain including volume measurement of the hippocampus, BOLD, and ASL perfusion scans. On entry, patients will have CDR stage of at least 0.5 and at least one abnormal imaging biomarker. CSF studies have demonstrated good sensitivity and specificity for MCI and dementia of the Alzheimer's type (Tapiola et al., 2009). Additionally, MRI volumetrics and perfusion scans have shown to be useful in differentiating subgroups of AD, PDD/DLB, and FTLD; these values are also responsive to change as patients progress form MCI to dementia (Targosz-Gajniak et al., 2013).

Exclusion Criteria

• Cognitive decline clearly related to an acute illness
• 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
• Any other neoplastic illness or illness characterized by neovascularity
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Neurological Associates of West Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sheldon Jordan, M.D.

Role: PRINCIPAL_INVESTIGATOR

Neurological Associates of West Los Angeles

Locations

Neurological Associates of West Los Angeles

Santa Monica, California, United States

Countries

United States

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Other Identifiers

ICSS-2018-018

Identifier Type: -

Identifier Source: org_study_id