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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
82
Ten 1ml injections of ALD-301 in the index calf and posterior, lower thigh
Ten 1ml injections of placebo in the index calf and posterior, lower thigh
Stanford University School of Medicine (Falk Cardiovascular Research Center)
Stanford, California, United States
University of Florida-Department of Medicine
Gainesville, Florida, United States
University of Miami-Interdisciplinary Stem Cell Institute
Miami, Florida, United States
Peak Walking Time (PWT)
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.
Time frame: Assessed at baseline and 6 months
Leg Collateral Count (Via Contrast Enhanced-MR)
The placebo adjusted average change in the number of collateral vessels over time.
Time frame: Assessed at baseline and 6 months
Peak Hyperemic Popliteal Flow (Phase Contrast MRA)
The placebo adjusted average change in peak hyperemic popliteal flow (mL/s) over time.
Time frame: Assessed at baseline and 6 months
Capillary Perfusion
The placebo adjusted average change in capillary perfusion over time.
Time frame: Assessed at baseline and 6 months
Pre-exercise Ankle-Brachial Index (ABI)
ABI is the ratio of the blood pressure at the ankle to the blood pressure of the upper arm. Pre-exercise ABI is collected routinely with the patient supine immediately prior to a treadmill test. This measure represents the placebo adjusted average change over time in arm and pedal (ankle) blood pressure. The reported value is the estimate from regression analysis of the slope of the placebo adjusted measure over the time course of the trial adjusted for baseline weight.
Time frame: Assessed as a trajectory (baseline, 3mos, and 6 mos)
Post-exercise Ankle-Brachial Index (ABI)
ABI is the ratio of the blood pressure at the ankle to the blood pressure of the upper arm. Post-exercise ABI is collected routinely with the patient supine immediately following a treadmill test. This measure represents the placebo adjusted average change over time in arm and pedal (ankle) blood pressure. The reported value is the estimate from regression analysis of the slope of the placebo adjusted measure over the time course of the trial adjusted for baseline weight.
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Orlando Health Inc.
Orlando, Florida, United States
Indiana Center for Vascular Biology and Medicine
Indianapolis, Indiana, United States
University of Louisville
Louisville, Kentucky, United States
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, United States
Clinical and Translational Science Institute at University of Minnesota
Minneapolis, Minnesota, United States
Texas Heart Institute
Houston, Texas, United States
Time frame: Assessed as a trajectory (baseline, 3mos, and 6 mos)
Claudication Onset Time (COT)
Claudication Onset Time (COT) is the walking time at which patients first experience leg pain during a treadmill test. The measure represents placebo adjusted average change over time (in minutes) in the time walked by a patient on a treadmill under standardized conditions before the onset of claudication symptoms, regardless of whether this is manifested or characterized as muscle pain, ache, cramp, numbness or fatigue. This does not include joint pain or other pain not associated with claudication. The reported value is the estimate from regression analysis of the slope of the placebo adjusted measure over the time course of the trial adjusted for baseline weight.
Time frame: Assessed as a trajectory (baseline, 3mos, and 6 mos)
Peak Walking Time (PWT)
The average change in 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.
Time frame: Assessed at baseline and 3 months
Peripheral Artery Questionnaire (PAQ)
The Peripheral Artery Questionnaire (PAQ) assesses subjective physical limitations, leg symptoms, social function, treatment satisfaction, and quality of life. It is administered as a self report. Higher scores are indicative of better outcome. The summary scores is compiled by taking the mean of five subscales generated from the original questions. Range: Minimum score is 11.1, maximum 85. The measure represents placebo adjusted average change in Peripheral Artery Questionnaire (PAQ) summary score assessed over time. The reported value is the estimate from regression analysis of the slope of the placebo adjusted measure over the time course of the trial adjusted for baseline weight.
Time frame: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos)
Walking Impairment Questionnaire (WIQ)-Walking Distance Score
The Walking Impairment Questionnaire (WIQ) assesses the severity of the subjective walking impairment on distance, speed, and stair climbing scales. It is administered as a self report. Range: Minimum score is 0.2, maximum 100. The measure represents the placebo adjusted average change in WIQ walking distance score assessed over time. The reported value is the estimate from regression analysis of the slope of the placebo adjusted measure over the time course of the trial adjusted for baseline weight.
Time frame: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos)
Walking Impairment Questionnaire (WIQ)- Walking Speed Score
The Walking Impairment Questionnaire (WIQ) assesses the severity of the subjective walking impairment on distance, speed, and stair climbing scales. It is administered as a self report. Range: Minimum score is 0, maximum 87. The measure represents the placebo adjusted average change in WIQ walking speed score assessed over time. The reported value is the estimate from regression analysis of the slope of the placebo adjusted measure over the time course of the trial adjusted for baseline weight.
Time frame: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos)
Walking Impairment Questionnaire (WIQ)-Ability to Climb Stairs Score
The Walking Impairment Questionnaire (WIQ) assesses the severity of the subjective walking impairment on distance, speed, and stair climbing scales. It is administered as a self report. Range: Minimum score is 0, maximum 100. The measure represents the placebo adjusted average change in WIQ ability to climb stairs score assessed over time. The reported value is the estimate from regression analysis of the slope of the placebo adjusted measure over the time course of the trial adjusted for baseline weight.
Time frame: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos)