Clinical trial NCT04202770: Focused Ultrasound and Exosomes to Treat Depression, Anxiety, and Dementias
Official title: Focused Ultrasound Delivery of Exosomes for Treatment of Refractory Depression, Anxiety, and Neurodegenerative Dementias
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Refractory Depression
Anxiety Disorders
Neurodegenerative Diseases
Lead sponsor: Neurological Associates of West Los Angeles
Sponsor class: OTHER
First posted: 2019-12-18
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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).
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: [trMDD] Beck Depression Inventory (BDI-II)
timeFrame: 8 weeks from baseline
measure: [Anxiety] Beck Anxiety Inventory (BAI)
timeFrame: 8 weeks from baseline
measure: [Dementia] Quick Dementia Rating Scale (QDRS)
timeFrame: 8 weeks from baseline
measure: [ALL] Global Rating of Change (GRC)
timeFrame: 8 weeks from baseline
Secondary outcomes:
measure: [trMDD] Patient Depression Questionnaire (PDQ-9)
timeFrame: 8 weeks from baseline
measure: [trMDD] Hamilton Depression Rating Scale (HAM-D)
timeFrame: 8 weeks from baseline
measure: [Anxiety] Hamilton Anxiety Rating Scale (HAM-A)
timeFrame: 8 weeks from baseline
measure: [Dementia] Repeatable Battery Assessment of Neuropsychological Status (RBANS) versions A-D
timeFrame: 8 weeks from baseline
measure: [Dementia] Montreal Cognitive Assessment (MoCA) versions 7.1-7.3
timeFrame: 8 weeks from baseline
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Neurological Associates of West Los Angeles
state: California
Study officials:
affiliation: Neurological Associates of West Los Angeles
name: Sheldon Jordan, M.D.
role: PRINCIPAL_INVESTIGATOR
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