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

January 18, 2013
May 15, 2014
June 2013
November 2014   (final data collection date for primary outcome measure)
  • 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.
  • Peak Walking Time (PWT) [ Time Frame: Assessed at baseline and 6 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The 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 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 average change in hyperemic fractional microvascular blood plasma volume over time.
Complete list of historical versions of study NCT01774097 on ClinicalTrials.gov Archive Site
  • 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.
  • Resting Ankle-Brachial Index (ABI) [ Time Frame: Assessed at baseline and 3 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Quantitate the relationship between the change over time in PWT and the change over time in perfusion using the general linear model.
Not Provided
Oximetry (cuff induced ischemia) [ Time Frame: Assessed at baseline and 6 months ] [ Designated as safety issue: No ]
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.
 
Patients With Intermittent Claudication Injected With ALDH Bright Cells
Clinical and MR Imaging Assessments in Patients With Intermittent Claudication Following Injection of Bone Marrow Derived ALDH Bright Cells

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Peripheral Artery Disease
  • Intermittent Claudication
  • 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
  • Biological: Placebo (vehicle)
    Ten 1ml injections of placebo in the index calf and posterior, lower thigh
    Other Names:
    • Placebo
    • Vehicle
    • HSA
    • Human Serum Albumin
  • Experimental: ALD-301
    Participants will receive ALD-301 via intramuscular injection
    Intervention: Biological: ALD-301
  • Placebo Comparator: Placebo (vehicle)
    Participants will receive placebo (vehicle)via intramuscular injection
    Intervention: Biological: Placebo (vehicle)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
80
May 2015
November 2014   (final data collection date for primary outcome measure)

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
Both
40 Years and older
No
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
United States
 
NCT01774097
CCTRN 581, UM1HL087318-06
Yes
Dr Lemuel A Moye III, The University of Texas Health Science Center, Houston
The University of Texas Health Science Center, Houston
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Aldagen
  • Center for Cell and Gene Therapy, Baylor College of Medicine
Study Chair: Robert Simari, MD Cardiovascular Cell Therapy Research Network
The University of Texas Health Science Center, Houston
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP