Clinical and MR Imaging Assessments in Patients With Intermittent Claudication Following Injection of Bone Marrow Derived ALDH Bright Cells
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 82
- 试验地点
- 18
- 主要终点
- Leg Collateral Count (Via Contrast Enhanced-MR)
研究概览
简要总结
The purpose of this study is to find out if aldehyde dehydrogenase bright (ALDHbr) cells taken from a patient's bone marrow can be placed safely, via intramuscular injections, into their affected calf and lower thigh muscles and improve blood flow and/or peak walking time in patients experiencing pain associated with blocked blood vessels in the leg.
详细描述
Peripheral Artery Disease (PAD) occurs when arteries in the arms and legs (most often the legs) become narrowed by plaque. Because of this plaque, patients with PAD are also at increased risk for heart attacks and strokes. Those with PAD often have intermittent claudication (blockage of blood vessels in the leg). This blockage decreases blood flow to the leg muscles, which can cause pain in one or both legs during exercise (such as during walking). Intermittent means the pain comes and goes. Because PAD interferes with circulation, worsening of this condition can increase pain in the leg; sometimes even during periods of rest.
Bone marrow contains special stem cells that may promote blood vessel growth, prevent cell death, and transform themselves into a number of tissues including new muscle. There is a small subpopulation of bone marrow mononuclear cells, called aldehyde dehydrogenase-bright (ALDHbr) cells, that is highly enriched in these types of stem cells. The enzyme in ALDHbr cells responds to damage signals and may play an important role in tissue repair.
In this study we investigate the safety and efficacy of bone marrow derived stem cells with particular characteristics in PAD patients with intermittent claudication and explore new end-points to evaluate therapeutic effects using novel MRI imaging modalities as well as traditional endpoints.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with atherosclerotic peripheral artery disease with classic claudication (exercise-induced pain, cramps, fatigue, or other equivalent discomfort involving large muscle groups of the leg(s) that is consistently relieved by rest) or atypical leg pain (exertional leg pain that does not begin at rest or does not resolve consistently with rest) as defined by the San Diego Claudication Questionnaire.
- •Age ≥40 years
- •Resting ankle-brachial index <0.90 or a resting toe-brachial index of <0.70 at baseline testing
- •Presence of significant stenosis or occlusion of infrainguinal arteries including the superficial femoral artery, popliteal artery and/or infrapopliteal arteries as determined by: Duplex ultrasound imaging (occlusion or focal doubling of peak systolic velocity of one or more affected segments) OR lower extremity computed Tomography Angiography (CTA) OR lower extremity magnetic resonance angiography (MRA) OR lower extremity catheter-based contrast arteriography. Each of these noninvasive and invasive anatomic assessments will identify patients with at least a 50% stenosis in the affected segment.
排除标准
- •Presence of any musculoskeletal disease, cardiac or pulmonary disease, or neurological disease that limits the patient's ability to walk to fulfill protocol requirements (claudication must be the consistent primary exercise limitation)
- •Inability to complete treadmill testing per protocol requirements.
- •Ability to walk for more than 12 minutes on the treadmill during treadmill testing.
- •Patients who identify both legs as equivocally symptomatic or alternate between symptomatic legs on the baseline treadmill tests.
- •Patients with critical limb ischemia (ischemic rest pain or ischemia-related non healing wounds or tissue loss (Rutherford categories 4-6).
- •Recent (<3 months) infrainguinal revascularization (surgery or endovascular revascularization) or revascularization planned during study period
- •Patients with a patent infrainguinal bypass graft in the index limb, with or without evidence of a hemodynamically significant stenosis or other defect (kinking, pseudoaneurysm, or fistula). Patients with an occluded infrainguinal bypass graft or a patent aortobifemoral or femoral-femoral bypass graft are NOT excluded.
- •Patients with >2+ lower extremity pitting edema
- •Patients with myelodysplastic syndrome (MDS)
- •Patients who are pregnant or lactating, planning to become pregnant in the next 12 months, or are unwilling to use acceptable forms of birth control during study participation.
- •Congestive Heart Failure hospitalization within the last 1 month prior to enrollment
- •Acute coronary syndrome in the last 1 month prior to enrollment
- •Human Immunodeficiency Virus positive, active Hepatitis B Virus or Hepatitis C Virus Disease
- •History of cancer within the last 5 years, except basal cell skin carcinoma
- •Any bleeding diathesis defined as an International Normalized Ratio ≥ 2.0 (off anticoagulation therapy) or history of platelet count less than 100,000 or hemophilia
- •Contraindication to magnetic resonance imaging (MRI) (including knee/tibial/fibular replacement hardware in the index leg) or known allergy to MRI contrast media
- •Chronic kidney disease [effective Glomerular Filtration Rate <30 by modification of diet in renal disease (MDRD) or Mayo or Cockcroft-Gault formula]
- •Uncontrolled diabetes [Hemoglobin A1C (HbA1C)>8.5]
- •Planned change to (initiate or terminate) active involvement in a supervised exercise program (e.g., with a trainer, exercise protocol, and goals, such as in a peripheral arterial disease, cardiac or pulmonary rehabilitation program) during study participation
- •Plans to change medical therapy during the duration of the study, (i.e. patients who use cilostazol should remain on a stable dose for four weeks prior to enrollment and should not change doses for the 6 months of the study duration.) As always, cilostazol can be discontinued if new heart failure or intolerance occurs during study participation.
- •Any condition requiring immunosuppressant medications (e.g., for treatment of organ transplants, psoriasis, Crohn's disease, alopecia areata).
- •History of inflammatory or progressively fibrotic conditions (e.g. rheumatoid arthritis, systemic lupus erythematosis, vasculitic disorders, idiopathic pulmonary fibrosis, retroperitoneal fibrosis).
- •Patients with any untreated stenosis > 70% of the distal aorta, common iliac, or external iliac arteries by CT, Angiography or MRI imaging will be excluded from enrollment (patients with previously successfully revascularized inflow stenoses may enroll in PACE). Subjects who were screen failures for a flow-limiting proximal lesion may be rescreened 3 months after successful angioplasty/stenting.
- •Inability to provide written informed consent due to cognitive or language barriers (interpreter permitted)
- •Concurrent enrollment in another clinical interventional investigative trial.
- •Presence of any clinical condition that in the opinion of the principal Investigator or the sponsor makes the patient not suitable to participate in the trial
结局指标
主要结局
Leg Collateral Count (Via Contrast Enhanced-MR)
时间窗: Assessed at baseline and 6 months
The placebo adjusted average change in the number of collateral vessels over time.
Peak Walking Time (PWT)
时间窗: Assessed at baseline and 6 months
The placebo adjusted average change over time in the maximum time (in minutes) walked by a patient on a treadmill under standardized conditions. The patient continues the test until walking can no longer be tolerated because of claudication symptoms.
Peak Hyperemic Popliteal Flow (Phase Contrast MRA)
时间窗: Assessed at baseline and 6 months
The placebo adjusted average change in peak hyperemic popliteal flow (mL/s) over time.
Capillary Perfusion
时间窗: Assessed at baseline and 6 months
The placebo adjusted average change in capillary perfusion over time.
次要结局
- Claudication Onset Time (COT)(Assessed as a trajectory (baseline, 3mos, and 6 mos))
- Peripheral Artery Questionnaire (PAQ)(Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos))
- Walking Impairment Questionnaire (WIQ)-Walking Distance Score(Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos))
- Walking Impairment Questionnaire (WIQ)- Walking Speed Score(Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos))
- Walking Impairment Questionnaire (WIQ)-Ability to Climb Stairs Score(Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos))
- Pre-exercise Ankle-Brachial Index (ABI)(Assessed as a trajectory (baseline, 3mos, and 6 mos))
- Post-exercise Ankle-Brachial Index (ABI)(Assessed as a trajectory (baseline, 3mos, and 6 mos))
- Peak Walking Time (PWT)(Assessed at baseline and 3 months)
研究者
Dr Lemuel A Moye III
Professor - School of Public Health
The University of Texas Health Science Center, Houston