Focused Ultrasound Delivery of Exosomes for Treatment of Refractory Depression, Anxiety, and Neurodegenerative Dementias
试验速览
- 阶段
- 不适用
- 状态
- 暂停
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- [trMDD] Beck Depression Inventory (BDI-II)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Exosomes (Other)
结局指标
主要结局
[trMDD] Beck Depression Inventory (BDI-II)
时间窗: 8 weeks from baseline
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.
[Anxiety] Beck Anxiety Inventory (BAI)
时间窗: 8 weeks from baseline
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.
[Dementia] Quick Dementia Rating Scale (QDRS)
时间窗: 8 weeks from baseline
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).
[ALL] Global Rating of Change (GRC)
时间窗: 8 weeks from baseline
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.
次要结局
- [trMDD] Patient Depression Questionnaire (PDQ-9)(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)
- [trMDD] Hamilton Depression Rating Scale (HAM-D)(8 weeks from baseline)