Patients With Intermittent Claudication Injected With ALDH Bright Cells (PACE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by The University of Texas Health Science Center, Houston
Sponsor:
Collaborators:
Aldagen
Center for Cell and Gene Therapy, Baylor College of Medicine
Information provided by (Responsible Party):
Dr Lemuel A Moye III, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT01774097
First received: January 18, 2013
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Peripheral Artery Disease
Intermittent Claudication
Biological: ALD-301
Biological: Placebo (vehicle)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Clinical and MR Imaging Assessments in Patients With Intermittent Claudication Following Injection of Bone Marrow Derived ALDH Bright Cells

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center, Houston:

Primary Outcome Measures:
  • Peak Walking Time (PWT) [ Time Frame: Assessed at baseline and 6 months ] [ Designated as safety issue: No ]
    The placebo adjusted 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 ] [ Designated as safety issue: No ]
    The placebo adjusted average change in the number of patent vessels over time.

  • Vascular Flow (Phase Contrast MRA) [ Time Frame: Assessed at baseline and 6 months ] [ Designated as safety issue: No ]
    The placebo adjusted average change in peak flow (mL/s) over time.

  • Perfusion (Cuff-induced Ischemia using Perfusion MR) [ Time Frame: Assessed at baseline and 6 months ] [ Designated as safety issue: No ]
    The placebo adjusted average change in hyperemic fractional microvascular blood plasma volume over time.


Secondary Outcome Measures:
  • Pre-exercise Ankle-Brachial Index (ABI) [ Time Frame: Assessed at baseline and 3 months ] [ Designated as safety issue: No ]
    The placebo adjusted average change over time in arm and pedal blood pressure will be obtained routinely with the patient supine immediately prior to the treadmill test.

  • Pre-exercise Ankle-Brachial Index (ABI) [ Time Frame: Assessed at baseline and 6 months ] [ Designated as safety issue: No ]
    The placebo adjusted 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 ] [ Designated as safety issue: No ]
    The placebo adjusted 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 ] [ Designated as safety issue: No ]
    The placebo adjusted 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 ] [ Designated as safety issue: No ]
    The placebo adjusted 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 ] [ Designated as safety issue: No ]
    The placebo adjusted 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 ] [ Designated as safety issue: No ]
    The placebo adjusted 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 ] [ Designated as safety issue: No ]
    Quantitate the relationship between the placebo adjusted 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 ] [ Designated as safety issue: No ]
    Quantitate the relationship between the placebo adjusted 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 ] [ Designated as safety issue: No ]
    Quantitate the relationship between the placebo adjusted change over time in PWT and the change over time in perfusion using the general linear model.

  • Walking Impairment Questionnaire (WIQ) [ Time Frame: Assessed at baseline and 1 month ] [ Designated as safety issue: No ]
    The placebo adjusted average change in WIQ score over time

  • Peripheral Artery Questionnaire (PAQ) [ Time Frame: Assessed at baseline and 1 month ] [ Designated as safety issue: No ]
    The placebo adjusted average change in PAQ score over time.

  • Walking Impairment Questionnaire (WIQ) [ Time Frame: Assessed at baseline and 3 months ] [ Designated as safety issue: No ]
    The placebo adjusted average change in WIQ score assessed over time

  • Peripheral Artery Questionnaire (PAQ) [ Time Frame: Assessed at baseline and 3 months ] [ Designated as safety issue: No ]
    The placebo adjusted average change in PAQ score over time

  • Walking Impairment Questionnaire (WIQ) [ Time Frame: Assessed at baseline and 6 months ] [ Designated as safety issue: No ]
    The placebo adjusted average change in WIQ score over time

  • Peripheral Artery Questionnaire (PAQ) [ Time Frame: Assessed at baseline and 6 months ] [ Designated as safety issue: No ]
    The placebo adjusted average change in PAQ score over time.


Estimated Enrollment: 80
Study Start Date: June 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ALD-301
Participants will receive ALD-301 via intramuscular injection
Biological: ALD-301
Ten 1ml injections of ALD-301 in the index calf and posterior, lower thigh
Other Names:
  • ALDH Bright Cells
  • ALDHbr
  • Aldehyde dehydrogenase-bright cells
Placebo Comparator: Placebo (vehicle)
Participants will receive placebo (vehicle)via intramuscular injection
Biological: Placebo (vehicle)
Ten 1ml injections of placebo in the index calf and posterior, lower thigh
Other Names:
  • Placebo
  • Vehicle
  • HSA
  • Human Serum Albumin

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Age ≥40 years
  3. Resting ankle-brachial index <0.90 or a resting toe-brachial index of <0.70 at baseline testing
  4. 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.

Exclusion Criteria:

  1. 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)
  2. Inability to complete treadmill testing per protocol requirements.
  3. Ability to walk for more than 11 minutes on the treadmill during treadmill testing.
  4. Patients who identify both legs as equivocally symptomatic or alternate between symptomatic legs on the baseline treadmill tests.
  5. Patients with critical limb ischemia (ischemic rest pain or ischemia-related non healing wounds or tissue loss (Rutherford categories 4-6).
  6. Recent (<3 months) infrainguinal revascularization (surgery or endovascular revascularization) or revascularization planned during study period
  7. Patients with a patent bypass graft in the index limb, with or without evidence of a hemodynamically significant stenosis or other defect (kinking, pseudoaneurysm, or fistula).
  8. Patients with >2+ lower extremity pitting edema
  9. Patients with myelodysplastic syndrome (MDS)
  10. 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.
  11. Congestive Heart Failure hospitalization within the last 1 month prior to enrollment
  12. Acute coronary syndrome in the last 1 month prior to enrollment
  13. Human Immunodeficiency Virus positive, active Hepatitis B Virus or Hepatitis C Virus Disease
  14. History of cancer within the last 5 years, except basal cell skin carcinoma
  15. 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
  16. Contraindication to magnetic resonance imaging (MRI) (including knee/tibial/fibular replacement hardware in the index leg) or known allergy to MRI contrast media
  17. Chronic kidney disease [effective Glomerular Filtration Rate <30 by modification of diet in renal disease (MDRD) or Mayo or Cockcroft-Gault formula]
  18. Uncontrolled diabetes [Hemoglobin A1C (HbA1C)>8.5]
  19. 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
  20. 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.
  21. Any condition requiring immunosuppressant medications (e.g., for treatment of organ transplants, psoriasis, Crohn's disease, alopecia areata).
  22. History of inflammatory or progressively fibrotic conditions (e.g. rheumatoid arthritis, systemic lupus erythematosis, vasculitic disorders, idiopathic pulmonary fibrosis, retroperitoneal fibrosis).
  23. 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.
  24. Inability to provide written informed consent due to cognitive or language barriers (interpreter permitted)
  25. Concurrent enrollment in another clinical interventional investigative trial.
  26. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01774097

Contacts
Contact: Lemuel A Moye, MD, PhD 832-721-6736 lemmoye@msn.com
Contact: Shelly L Sayre, MPH 713-500-9529 Shelly.L.Sayre@uth.tmc.edu

Locations
United States, California
Stanford University School of Medicine (Falk Cardiovascular Research Center) Recruiting
Stanford, California, United States, 94305
Contact: Fouzia Khan    650-736-1410    fouziak@stanford.edu   
Principal Investigator: Phil Yang, MD         
United States, Florida
University of Florida-Department of Medicine Recruiting
Gainesville, Florida, United States, 32610
Contact: Dana Leach, DNP    352-273-8930    Dana.Leach@medicine.ufl.edu   
Principal Investigator: Carl Pepine, MD         
University of Miami-Interdisciplinary Stem Cell Institute Recruiting
Miami, Florida, United States, 33101
Contact: Darcy DiFede, RN, BSN    305-243-9106    ddifede@med.miami.edu   
Principal Investigator: Josh Hare, MD         
United States, Indiana
Indiana Center for Vascular Biology and Medicine Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Pat G'Sell    317-278-6585    pgsell@iu.edu   
Contact: Kristen Wanczyk    317-278-0130    keevans@iu.edu   
Principal Investigator: Michael Murphy, MD         
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact: Shari Williams    502-407-3259    SLWILL06@louisville.edu   
Principal Investigator: Roberto Bolli, MD         
United States, Minnesota
Minneapolis Heart Institute Foundation Recruiting
Minneapolis, Minnesota, United States, 55407
Contact: JoAnne Goldman, RT, RCIS, CCRC    612-863-3793    joanne.goldman@allina.com   
Contact: Sarah Smith, BS, CCRC    612-863-6286    Sarah.Smith2@allina.com   
Principal Investigator: Jason Alexander, MD         
Clinical and Translational Science Institute at University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Barb Bruhn-Ding, RN    612-625-5949    bruhn028@umn.edu   
Contact: Emily Caldwell, RN    612-626-3656    caldw076@umn.edu   
Principal Investigator: Alan Hirsch, MD         
United States, Texas
Texas Heart Institute Recruiting
Houston, Texas, United States, 77030
Contact: Jennifer Chambers    832-355-9408    jchambers@texasheart.org   
Contact: Nichole Piece    832-355-9173 or 1-866-924-7836    npiece@texasheart.org   
Principal Investigator: Emerson Perin, MD, PhD         
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Aldagen
Center for Cell and Gene Therapy, Baylor College of Medicine
Investigators
Study Chair: Robert Simari, MD Cardiovascular Cell Therapy Research Network
  More Information

Additional Information:
Publications:
Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM Jr, White CJ, White J, White RA, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B; American Association for Vascular Surgery; Society for Vascular Surgery; Society for Cardiovascular Angiography and Interventions; Society for Vascular Medicine and Biology; Society of Interventional Radiology; ACC/AHA Task Force on Practice Guidelines Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease; American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; Vascular Disease Foundation. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation. 2006 Mar 21;113(11):e463-654. Review.

Responsible Party: Dr Lemuel A Moye III, Professor - School of Public Health, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT01774097     History of Changes
Other Study ID Numbers: CCTRN 581, UM1HL087318-06
Study First Received: January 18, 2013
Last Updated: May 15, 2014
Health Authority: United States: Food and Drug Administration
United States: Data and Safety Monitoring Board
United States: Institutional Review Board

Keywords provided by The University of Texas Health Science Center, Houston:
Peripheral Artery Disease
Intermittent Claudication
Vascular Flow
Autologous Stem Cells
ALDH cells
Claudicants
PAD
Peak Walking Time
MRI
Anatomy
Perfusion

Additional relevant MeSH terms:
Intermittent Claudication
Peripheral Arterial Disease
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Peripheral Vascular Diseases
Arteriosclerosis
Signs and Symptoms
Atherosclerosis
Albunex
Contrast Media
Diagnostic Uses of Chemicals
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014