A Phase I, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Potential Efficacy of Allogeneic Human Mesenchymal Stem Cell Infusion Versus Placebo in Patients With Treatment Resistant Depression.
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Incidence of any treatment-emergent serious adverse events (TE-SAEs)
研究概览
简要总结
This study is intended to evaluate the safety and potential efficacy of Allogeneic Human Mesenchymal Stem Cell Infusion versus placebo in patients with Treatment Resistant Depression.
详细描述
This is a phase I study, with eight subjects in the pilot phase and eighty (80) subjects fulfilling all inclusion/exclusion criteria's will be randomly assigned to receive allogeneic Human Mesenchymal Stem Cell (hMSCs) or placebo in a 1:1 blinded fashion.
The 8 subjects in the pilot phase will receive a single infusion of 100 million hMSCs.
40 patients will receive a single administration of allogeneic hMSCs and another 40 patients will receive a single administration of Placebo in a 1:1 blinded fashion.
Following infusion, patients will be followed at 2, 4, 6, 8, 10 and 12 week's post-infusion to complete all safety and efficacy assessments. During these 12 weeks starting after the week 2 visit subjects will have a phone call in-between their visits. Patients will additionally be followed for up to 12 months post-infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide written informed consent.
- •Subjects age equal or greater than 18 and equal or less than 75 years at the time of signing the Informed Consent Form.
- •Diagnosis of Treatment resistant depression (Failed at least two adequate trials of antidepressant monotherapy or antidepressant augmentation with an antipsychotic or lithium during the current episode)
- •Patients who are receiving a third or more treatment will only be entered if they have not responded to the current treatment.
- •Experiencing a current Major Depressive Episode (fulfilling Structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders (DSM V) criteria per Structured Clinical Interview for DSM (SCID) for categorical diagnosis, and the Hamilton Depression Rating Scale for Depression (HAM-D))
- •Hamilton Depression Rating Scale 21-item score greater than 18
- •Adequacy of previous failed antidepressant trials will be defined using standard criteria by Massachusetts General Hospital (MGH) of patients with a score greater than or equal to 2.5
- •Increased inflammation ([Serum CRP] greater than 3.0 mg/L)
排除标准
- •In order to participate in this study, a patient Must Not:
- •Women who are pregnant, nursing, or of childbearing potential, while not practicing effective contraceptive methods. (Female subjects of childbearing potential must undergo a serum or urine pregnancy test at screening and within 36 hours prior to infusion.)
- •Inability to perform any of the assessments required.
- •Have clinically significant abnormal screening laboratory values, including but not limited to: hemoglobin <8 g/dl, white blood cell count <3000/mm3, platelets<80,000/mm3, INR > 1.5 not due to a reversible cause (i.e. Coumadin), aspartate transaminase, alanine transaminase, or alkaline phosphatase > 3 times upper limit of normal, total bilirubin > 1.8 mg/dl (unless due to a benign cause).
- •Active medical condition that could cause or exacerbate depressive symptoms (e.g., hypothyroidism, anemia)
- •Serious comorbid illness or any other condition (Such as bipolar, schizophrenia or schizoaffective disorder) that, in the opinion of the investigator, may compromise the safety or compliance of the subject or preclude successful completion of the study.
- •Have acute suicidality
- •Prior history of a suicide attempt, within the past year.
- •Active psychotic disorder, eating disorder, or substance use disorder within 6 months of enrollment
- •Treatment with any medication that, in the opinion of the Investigator, may compromise the safety of the subject or affect the validity of the data or the study endpoints.
- •First major depressive episode after 50 years of age.
- •Have known allergies to penicillin or streptomycin.
- •Have hypersensitivity to dimethyl sulfoxide (DMSO).
- •Have a clinical history of malignancy within 5 years (i.e., subjects with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma.
- •Have a non-pulmonary condition that limits lifespan to < 1 year.
- •Have a history of drug or alcohol abuse within the past 24 months.
- •Be serum positive for HIV, hepatitis BsAg or Viremic hepatitis C.
研究组 & 干预措施
Allogeneic hMSCs
Forty (40) subjects will be treated with a single administration of allogeneic Human Mesenchymal Stem Cell (hMSCs): 100 x 10^6 (100 million) allo-hMSCs of cells delivered via a single peripheral intravenous infusion.
干预措施: Allo-hMSCs (Drug)
Placebo
Forty (40) subjects will be treated with a placebo administration consisting of 1% human albumin serum in Plasma-Lyte A delivered via a single peripheral intravenous infusion.
干预措施: Placebo (Drug)
Pilot - Allogeneic hMSCs
Eight (8) subjects will be treated with a single administration of allogeneic Human Mesenchymal Stem Cell (hMSCs): 100 x 10^6 (100 million) allo-hMSCs of cells delivered via a single peripheral intravenous infusion.
干预措施: Allo-hMSCs (Drug)
结局指标
主要结局
Incidence of any treatment-emergent serious adverse events (TE-SAEs)
时间窗: One month post infusion
defined as a composite of acute suicidality, and hospitalization for suicide attempts.
次要结局
- Reduction of Inflammation(Week 12)
研究者
Joshua M Hare
Sponsor - Investigator
University of Miami