Autologous Bone Marrow Mononuclear Cell Administration for Lower Extremity Compartment Syndrome Injury
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Efficacy as determined by muscle strength
研究概览
简要总结
This is a phase 1 study to assess safety and tolerability of intramuscular administration of two different doses of autologous bone marrow mononuclear cells (BM-MNCs) for treatment of lower extremity injury complicated by compartment syndrome injury.
详细描述
The primary objectives are to assess safety and tolerability of a high and low dose of autologous bone marrow mononuclear cells. Secondary objectives include evaluation of potential responses of the BM-MNC therapy.
This is a two-stage, randomized, unblinded, multicenter (two sites), controlled phase 1 clinical trial to evaluate the safety of two different doses of intramuscular injections of autologous bone marrow mononuclear cells, commonly known as a type of stem cell. Acute compartment syndrome injury is a mixed soft tissue injury due to a trauma that causes edema leading to excessive pressure in the muscle compartment. This type of injury frequently results in permanent reduction in function and disability.
A total of 18 participants that have undergone a fasciotomy for treatment of a lower leg compartment syndrome will be enrolled with 6 assigned to the control (observational) group, 6 to the low cell-dose group and 6 to the high cell-dose group. The treatment arm will receive a single dose (high or low) of autologous BM-MNCs 5 - 9 days post injury and fasciotomy and a minimum of 3 months of standard of care physical rehabilitation. An observational control arm will not receive cells post fasciotomy but will undergo a standard of care course of physical therapy and will be followed for comparison to assess early safety signals and potential benefit.
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
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Females and males 18 - 70 years old
- •Has single or multiple compartment syndrome of the lower leg that includes the anterior tibial compartment
- •Trauma patients with lower extremity CS requiring fasciotomy that can be treated with autologous BM-MNC therapy on day 5-9 post-fasciotomy
- •Ability to sign an informed patient consent form
- •Access and willingness to complete a standard of care course of rehabilitation therapy and 24 months follow-up evaluations
- •Ability to close the fasciotomy wound per physician assessment
- •Anterior compartment muscle volume between 100 - 280 cc as determined by MRI/CT
- •Within the institutions' clinical reference ranges for HbA1C
- •Negative HIV test
- •· - Non-fracture, closed fracture or compound fracture type I (wound less than 1cm & compound from within out) (Gustilo-Anderson classification)
- •Female subjects must be of non-childbearing potential or must be using adequate contraception
- •If female subject is of childbearing potential, subject must have a negative pregnancy test at screening
- •Willing and able to adhere to the study schedule
排除标准
- •Prior compartment syndrome of same limb;
- •Active malignancy or has undergone treatment for a malignancy in the preceding 5 years as indicated in past medical history or self-report if medical records do not accompany subject or are unable to be collected (basal cell carcinoma non-exclusionary);
- •HIV positive as indicated by past medical history, self-report, or positive HIV test;
- •Diagnosis of Type 1 or Type 2 diabetes with elevated HbA1C consistent with diabetes;(controlled diabetes acceptable, diabetes medication for other diagnosis acceptable)
- •Diagnosis of chronic lower extremity vascular disease as diagnosed by current physician diagnosis, indicated in past medical history, or self-report if medical records do not accompany subject or are unable to be collected;
- •Patients unable to sign an informed patient consent;
- •Anticipated amputation of involved limb;
- •Neurological conditions (i.e. spinal cord injury or traumatic brain injury) that may prevent full participation in CS rehabilitation or potentially confound study outcome measures (i.e. balance and gait) per physician discretion
- •Current systemic infection;
- •Local infection of the involved muscle group;
- •Use of ventilator that would preclude rehabilitation protocols;
- •Lack of access or unwillingness to complete standard of care course of physical therapy rehabilitation;
- •Life expectancy 12 months or less;
- •Bone marrow disorders (i.e. leukemia, aplastic anemia, lymphoma) ;
- •Inability to close the fasciotomy wound or lower extremity burns that may affect wound closure
- •Extensive tissue loss due to debridement resulting in insufficient residual tissue for stem cell administration and subsequent engraftment
- •Lower extremity compound fracture type II or III (Gustilo-Anderson classification);
- •Anterior tibialis muscle volume less than 100 cc or greater than 280 cc as determined by MRI/CT;
- •Evidence of any past or present clinically significant medical condition that would impair wound healing
- •History or clinical manifestations of significant renal, hepatic, cardiovascular, metabolic, neurologic, psychiatric, or other condition that would preclude participation in the study as determined by the investigator or the investigator's designee;
- •Any reason, considered by the principal investigator or designee, to preclude subject enrollment in the study that might represent a threat to the subject's health or safety.
研究组 & 干预措施
Autologous BM-MNCs High Dose
Administration of autologous bone marrow mononuclear cells at High dose (700,000 cells/cc of tissue)
干预措施: Intramuscular administration of autologous BM-MNCs (Biological)
Autologous BM-MNCs Low Dose
Administration of autologous bone marrow mononuclear cells at a Low dose (350,000 cells/cc of tissue)
干预措施: Intramuscular administration of autologous BM-MNCs (Biological)
结局指标
主要结局
Efficacy as determined by muscle strength
时间窗: 6 weeks, 3 months, 6 months, and 12 months
Change in muscle strength compared to baseline and contralateral leg as measured by manual muscle testing and Biodex.
Safety as determined by incidence of combined adverse events related to study agent intervention
时间窗: Enrollment through 24 months
Local and systemic reactions, serious adverse events and unexpected serious adverse events.
次要结局
- Questionnaire - Physical Activity(Baseline through 24 months)
- Lower extremity sensation(Baseline through 12 months)
- Ankle range of motion(Baseline through 12 months)
- Safety as determined by evidence of tumor formation(Baseline through 12 months)
- Efficacy as determined by muscle regeneration(Baseline through 12 months)
- Nerve conduction(Baseline and 6 months)
- Gait analysis(Week 6 through 12 months)
- Gait speed(Week 6 through 12 months)
- Questionnaire - Pain(Baseline through 24 months)
- Wound healing(Baseline through 12 months)
- Gait endurance(Week 6 through 12 months)
- Questionnaire - Function(Baseline through 24 months)
- Balance(Week 6 through 12 months)
研究者
Kenton W. Gregory
Director, Oregon Center for Regenerative Medicine
Oregon Health and Science University