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History of Changes for Study: NCT01774097
Patients With Intermittent Claudication Injected With ALDH Bright Cells (PACE)
Latest version (submitted March 10, 2017) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 January 18, 2013 None (earliest Version on record)
2 June 19, 2013 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 July 12, 2013 Contacts/Locations and Study Status
4 August 5, 2013 Recruitment Status, Study Status, Contacts/Locations and Sponsor/Collaborators
5 August 8, 2013 Sponsor/Collaborators and Study Status
6 August 13, 2013 Recruitment Status, Contacts/Locations and Study Status
7 September 3, 2013 Contacts/Locations and Study Status
8 December 2, 2013 Contacts/Locations and Study Status
9 May 15, 2014 Outcome Measures, Conditions, Study Status, Contacts/Locations, Eligibility, Study Description and Sponsor/Collaborators
10 November 3, 2014 Study Status and Contacts/Locations
11 February 12, 2015 Study Status, References and Eligibility
12 May 4, 2015 Study Status
13 November 3, 2015 Study Status and Contacts/Locations
14 January 11, 2016 Recruitment Status, Study Status, Contacts/Locations and Study Design
15 June 27, 2016 Study Status
16 September 14, 2016 Study Status
17 October 13, 2016 Outcome Measures, Study Status and Study Identification
18 March 10, 2017 Recruitment Status, Study Status, Outcome Measures and Results
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Study NCT01774097
Submitted Date:  January 18, 2013 (v1)

Open or close this module Study Identification
Unique Protocol ID: CCTRN 581
Brief Title: Patients With Intermittent Claudication Injected With ALDH Bright Cells (PACE)
Official Title: Clinical and MR Imaging Assessments in Patients With Intermittent Claudication Following Injection of Bone Marrow Derived ALDH Bright Cells
Secondary IDs: UM1HL087318-06 [U.S. NIH Grant/Contract]
Open or close this module Study Status
Record Verification: January 2013
Overall Status: Not yet recruiting
Study Start: March 2013
Primary Completion: August 2014 [Anticipated]
Study Completion: February 2015 [Anticipated]
First Submitted: January 18, 2013
First Submitted that
Met QC Criteria:
January 18, 2013
First Posted: January 23, 2013 [Estimate]
Last Update Submitted that
Met QC Criteria:
January 18, 2013
Last Update Posted: January 23, 2013 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: The University of Texas Health Science Center, Houston
Responsible Party: Principal Investigator
Investigator: Dr Lemuel A Moye III
Official Title: Professor - School of Public Health
Affiliation: The University of Texas Health Science Center, Houston
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Aldagen
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
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 Description:

Peripheral Arterial 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.

Open or close this module Conditions
Conditions: Peripheral Arterial Disease
Intermittent Claudication
Keywords: Peripheral Arterial Disease
Intermittent Claudication
Autologous Stem Cells
ALDH cells
Claudicants
PAD
Peak Walking Time
MRI
Vascular Flow
Anatomy
Perfusion
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 80 [Anticipated]
Open or close this module Arms and Interventions
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
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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.
2. 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.
3. Vascular Flow (Phase Contrast MRA)
[ Time Frame: Assessed at baseline and 6 months ]

The average change in peak flow (mL/s) over time.
4. 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.
Secondary Outcome Measures:
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
Other Outcome Measures:
1. Oximetry (cuff induced ischemia)
[ Time Frame: Assessed at baseline and 6 months ]

The average change over time in washout time (seconds) between the two groups after five minutes cuff-induced ischemia - this experimental endpoint will only be performed at clinical sites that are qualified to participate in this sub-study by the MRI core lab.
Open or close this module Eligibility
Minimum Age: 40 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Patients with atherosclerotic peripheral arterial 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 less than <0.90
  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
  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) 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. Current 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) for more than 2 weeks within the prior 6 weeks or plans to join such a 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
Open or close this module Contacts/Locations
Central Contact Person: Lemuel A Moye, MD, PhD
Telephone: 832-721-6736
Email: lemmoye@msn.com
Central Contact Backup: Shelly L Sayre, MPH
Telephone: 713-500-9529
Email: Shelly.L.Sayre@uth.tmc.edu
Study Officials: Robert Simari, MD
Study Chair
Cardiovascular Cell Therapy Research Network
Locations: United States, California
Stanford University School of Medicine (Falk Cardiovascular Research Center)
Stanford, California, United States, 94305
Contact:Contact: Fouzia Khan 650-736-1410 fouziak@stanford.edu
Contact:Principal Investigator: John Cooke, MD
United States, Florida
University of Florida-Department of Medicine
Gainesville, Florida, United States, 32610
Contact:Contact: Tempa Curry 352-273-8937 Tempa.Curry@medicine.ufl.edu
Contact:Contact: Dana Leach 352-256-3924 Dana.Leach@medicine.ufl.edu
Contact:Principal Investigator: Carl Pepine, MD
University of Miami-Interdisciplinary Stem Cell Institute
Miami, Florida, United States, 33101
Contact:Contact: Darcy Velazquez, RN, BSN 305-243-7444 DVelazqu@med.miami.edu
Contact:Principal Investigator: Josh Hare, MD
United States, Indiana
Indiana Center for Vascular Biology and Medicine
Indianapolis, Indiana, United States, 46202
Contact:Contact: Pat G'Sell 317-278-6585 pgsell@iupui.edu
Contact:Contact: Judy Foltz 317-962-0531 jfoltz@iupui.edu
Contact:Principal Investigator: Michael Murphy, MD
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
Contact:Contact: Tina Collins 502-587-4106 brcoll01@louisville.edu
Contact:Principal Investigator: Roberto Bolli, MD
United States, Minnesota
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, United States, 55407
Contact:Contact: JoAnne Goldman, RT, RCIS, CCRC 612-863-3793 joanne.goldman@allina.com
Contact:Principal Investigator: Tim Henry, MD
United States, Texas
Texas Heart Institute
Houston, Texas, United States, 77030
Contact:Contact: Casey Kappenman 832-355-9054 ckappenman@texasheart.org
Contact:Contact: Nichole Piece 832-355-9173 or 1-866-924-7836 npiece@texasheart.org
Contact:Principal Investigator: Emerson Perin, MD, PhD
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations: 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. PubMed 16549646
Perin EC, Silva G, Gahremanpour A, Canales J, Zheng Y, Cabreira-Hansen MG, Mendelsohn F, Chronos N, Haley R, Willerson JT, Annex BH. A randomized, controlled study of autologous therapy with bone marrow-derived aldehyde dehydrogenase bright cells in patients with critical limb ischemia. Catheter Cardiovasc Interv. 2011 Dec 1;78(7):1060-7. doi: 10.1002/ccd.23066. Epub 2011 May 18. PubMed 21594960
Links: Description: Cardiovascular Cell Therapy Research Network
Description: National Heart, Lung, and Blood Institute
Available IPD/Information:

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