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

NCT04202770 | Suspended

• 1 other identifier: ICSS-2018-018
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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.

Conditions

Refractory Depression; Anxiety Disorders; Neurodegenerative Diseases

Outcome Measures

Primary Outcomes (4)

• [trMDD] Beck Depression Inventory (BDI-II)

  The BDI-II is a 21-question multiple-choice self-report inventory. Each question involves four possible responses, ranging in intensity from "0" (this item does not apply) to "3" (this item applies severely). The test is scored as the sum of all of the response values; this number is used to determine the severity of depressive symptoms. A score of 0 to 3 is possible for each question with a maximum total score of 63 points. The standard cutoff scores are as follows: 0-13 total points = minimal depression; 14-19 total points = mild depression; 20-28 total points = moderate depression; and 29-63 total points = severe depression. A reduction in the total score by at least 30% is considered to be clinically significant.

  8 weeks from baseline

• [Anxiety] Beck Anxiety Inventory (BAI)

  The BAI is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety symptoms. Each of the 21 items asks whether the patient has experienced various anxiety symptoms in the last two weeks, and if so, how severely. Each question/answer is scored on a scale value of "0" (not at all) to "3" (severely). Higher total scores indicate more severe anxiety symptoms. The maximum total score possible is 63 points. The standard cutoff scores are: 0-7 = minimal anxiety; 8-15 = mild anxiety; 16-25 = moderate anxiety; 26-63 = severe anxiety. A reduction in score by at least 30% is considered clinically meaningful.

  8 weeks from baseline

• [Dementia] Quick Dementia Rating Scale (QDRS)

  The Quick Dementia Rating Scale (QDRS) is an interview-based tool administered by study officials to participants' caregivers used to obtain observations from a consistent source. The QDRS form consists of 10 categorical questions (5 cognitive, 5 functional), each with 5 detailed options depicting the level of impairment as either 0 (normal), 0.5 (mild/inconsistent impairment), 1 (mild/consistent impairment), 2 (moderate impairment), or 3 (severe impairment). Based on the conversion table outlined in Dr. James Galvin's research (2015), total QDRS scores were converted to Clinical Dementia Rating (CDR) scale levels ranging from 0 (normal aging), 0.5 (mild cognitive impairment), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia).

  8 weeks from baseline

• [ALL] Global Rating of Change (GRC)

  The GRC consists of a single likert-scale ranging from "-5" (very much worse) to "0" (neutral/no change) to "5" (very much better). The GRC is obtained in an interview format to assess a patient's perceived change in status following a treatment. A score that is at least 2 or greater is considered to indicate clinically significant change.

  8 weeks from baseline

Secondary Outcomes (5)

• [trMDD] Patient Depression Questionnaire (PDQ-9)

  8 weeks from baseline

• [trMDD] Hamilton Depression Rating Scale (HAM-D)

  8 weeks from baseline

• [Anxiety] Hamilton Anxiety Rating Scale (HAM-A)

  8 weeks from baseline

• [Dementia] Repeatable Battery Assessment of Neuropsychological Status (RBANS) versions A-D

  8 weeks from baseline

• [Dementia] Montreal Cognitive Assessment (MoCA) versions 7.1-7.3

  8 weeks from baseline

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Other: Exosomes

Interventions

Exosomes OTHER

Focused ultrasound delivery of intravenously-infused exosomes

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• Neurological Associates of West Los Angeles: lead

Study Sites (1)

Neurological Associates of West Los Angeles

Santa Monica, California, 90403, United States

Location

Related Publications (38)

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MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Anxiety Disorders; Neurodegenerative Diseases

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Nervous System Diseases

Study Officials

• Sheldon Jordan, M.D.

  Neurological Associates of West Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The present study is being undertaken as an open-label study to evaluate the safety and feasibility of exosomes and concurrent focused ultrasound as an intervention for patients with refractory depression, anxiety, and cognitive impairment due to a neurodegenerative disease (e.g., Alzheimer's).

Study Record Dates

• First Submitted: December 16, 2019
• First Posted: December 18, 2019
• Study Start: December 1, 2019
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: September 28, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)