Clinical Trial: Patients With Intermittent Claudication Injected With ALDH Bright Cells

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Clinical and MR Imaging Assessments in Patients With Intermittent Claudication Following Injection of Bone Marrow Derived ALDH Bright Cells

Brief Summary: 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.

Detailed Summary:

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.

Current Primary Outcome:

• Peak Walking Time (PWT) [ Time Frame: 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.
• Leg Collateral Count (Via Contrast Enhanced-MR) [ Time Frame: Assessed at baseline and 6 months ]
  The placebo adjusted average change in the number of collateral vessels over time.
• Peak Hyperemic Popliteal Flow (Phase Contrast MRA) [ Time Frame: Assessed at baseline and 6 months ]
  The placebo adjusted average change in peak hyperemic popliteal flow (mL/s) over time.
• Capillary Perfusion [ Time Frame: Assessed at baseline and 6 months ]
  The placebo adjusted average change in capillary perfusion over time.

Original Primary Outcome:

• Peak Walking Time (PWT) [ Time Frame: Assessed at baseline and 6 months ]
  The average change over time in the maximum time (in seconds) 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.
• Leg collateral artery anatomy (via contrast enhanced-MR) [ Time Frame: Assessed at baseline and 6 months ]
  The average change in the number of patent vessels over time.
• Vascular Flow (Phase Contrast MRA) [ Time Frame: Assessed at baseline and 6 months ]
  The average change in peak flow (mL/s) over time.
• Perfusion (Cuff-induced Ischemia using Perfusion MR) [ Time Frame: Assessed at baseline and 6 months ]
  The average change in hyperemic fractional microvascular blood plasma volume over time.

Current Secondary Outcome:

• Pre-exercise Ankle-Brachial Index (ABI) [ Time Frame: Assessed as a trajectory (baseline, 3mos, and 6 mos) ]
  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.
• Post-exercise Ankle-Brachial Index (ABI) [ Time Frame: Assessed as a trajectory (baseline, 3mos, and 6 mos) ]
  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.
• Claudication Onset Time (COT) [ Time Frame: Assessed as a trajectory (baseline, 3mos, and 6 mos) ]
  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.
• Peak Walking Time (PWT) [ Time Frame: Assessed at baseline and 3 months ]
  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.
• Peripheral Artery Questionnaire (PAQ) [ Time Frame: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos) ]
  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.
• Walking Impairment Questionnaire (WIQ)-Walking Distance Score [ Time Frame: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos) ]
  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.
• Walking Impairment Questionnaire (WIQ)- Walking Speed Score [ Time Frame: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos) ]
  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.
• Walking Impairment Questionnaire (WIQ)-Ability to Climb Stairs Score [ Time Frame: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos) ]
  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.

Original Secondary Outcome:

• Resting Ankle-Brachial Index (ABI) [ Time Frame: Assessed at baseline and 3 months ]
  The average change over time in arm and pedal blood pressure will be obtained routinely with the patient supine immediately prior to the treadmill test.
• Resting Ankle-Brachial Index (ABI) [ Time Frame: Assessed at baseline and 6 months ]
  The average change over time in arm and pedal blood pressure will be obtained routinely with the patient supine immediately prior to the treadmill test.
• Post-exercise Ankle-Brachial Index (ABI) [ Time Frame: Assessed at baseline and 3 months ]
  The average change over time in arm and pedal blood pressure will be obtained routinely with the patient supine immediately following the treadmill test.
• Post-exercise Ankle-Brachial Index (ABI) [ Time Frame: Assessed at baseline and 6 months ]
  The average change over time in arm and pedal blood pressure will be obtained routinely with the patient supine immediately following the treadmill test.
• Claudication Onset Time (COT) [ Time Frame: Assessed at baseline and 3 months ]
  The average change over time (in seconds) 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.
• Claudication Onset Time (COT) [ Time Frame: Assessed at baseline and 6 months ]
  The average change over time (in seconds) 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.
• Peak Walking Time (PWT) [ Time Frame: Assessed at baseline and 3 months ]
  The average change in maximum time (in seconds) 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.
• Relationship between PWT and leg collateral artery anatomy [ Time Frame: Assessed at baseline and 6 months ]
  Quantitate the relationship between the change over time in PWT and the change over time in leg collateral artery anatomy using the general linear model.
• Relationship between PWT and Vascular Flow [ Time Frame: Assessed at baseline and 6 months ]
  Quantitate the relationship between the change over time in PWT and the change over time in vascular flow using the general linear model.
• Relationship between PWT and Perfusion [ Time Frame: Assessed at baseline and 6 months ]
  Quantitate the relationship between the change over time in PWT and the change over time in perfusion using the general linear model.

Dates:
Date Received: January 18, 2013
Date Started: June 2013
Date Completion:
Last Updated: March 10, 2017
Last Verified: March 2017