Patients With Intermittent Claudication Injected With ALDH Bright Cells (PACE)
This study is not yet open for participant recruitment.
Verified January 2013 by The University of Texas Health Science Center, Houston
Sponsor:
The University of Texas Health Science Center, Houston
Collaborators:
Aldagen
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: NA
Last verified: January 2013
History: No changes posted
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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 Arterial 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 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.
Secondary Outcome Measures:
- 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.
Other Outcome Measures:
- 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.
| Estimated Enrollment: | 80 |
| Study Start Date: | March 2013 |
| Estimated Study Completion Date: | February 2015 |
| Estimated Primary Completion Date: | August 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:
|
|
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:
|
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.
Eligibility| Ages Eligible for Study: | 40 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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.
- Age ≥40 years
- Resting ankle-brachial index less than <0.90
- 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:
- 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)
- Inability to complete treadmill testing per protocol requirements.
- Ability to walk for more than 11 minutes on the treadmill during treadmill testing.
- Patients who identify both legs as equivocally symptomatic or alternate between symptomatic legs on the baseline treadmill tests.
- Patients with critical limb ischemia (ischemic rest pain or ischemia-related non healing wounds or tissue loss (Rutherford categories 4-6).
- Recent (<3 months) infrainguinal revascularization (surgery or endovascular revascularization) or revascularization planned during study period
- 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).
- Patients with >2+ lower extremity pitting edema
- Patients with myelodysplastic syndrome (MDS)
- 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.
- Congestive Heart Failure hospitalization within the last 1 month prior to enrollment
- Acute coronary syndrome in the last 1 month prior to enrollment
- Human Immunodeficiency Virus positive, active Hepatitis B Virus or Hepatitis C Virus
- History of cancer within the last 5 years, except basal cell skin carcinoma
- 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
- Contraindication to magnetic resonance imaging (MRI) or known allergy to MRI contrast media
- Chronic kidney disease [effective Glomerular Filtration Rate <30 by modification of diet in renal disease (MDRD) or Mayo or Cockcroft-Gault formula]
- Uncontrolled diabetes [Hemoglobin A1C (HbA1C)>8.5]
- 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
- 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.
- Any condition requiring immunosuppressant medications (e.g., for treatment of organ transplants, psoriasis, Crohn's disease, alopecia areata).
- History of inflammatory or progressively fibrotic conditions (e.g. rheumatoid arthritis, systemic lupus erythematosis, vasculitic disorders, idiopathic pulmonary fibrosis, retroperitoneal fibrosis).
- 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.
- Inability to provide written informed consent due to cognitive or language barriers (interpreter permitted)
- Concurrent enrollment in another clinical interventional investigative trial.
- 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
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) | Not yet recruiting |
| Stanford, California, United States, 94305 | |
| Contact: Fouzia Khan 650-736-1410 fouziak@stanford.edu | |
| Principal Investigator: John Cooke, MD | |
| United States, Florida | |
| University of Florida-Department of Medicine | Not yet recruiting |
| Gainesville, Florida, United States, 32610 | |
| Contact: Tempa Curry 352-273-8937 Tempa.Curry@medicine.ufl.edu | |
| Contact: Dana Leach 352-256-3924 Dana.Leach@medicine.ufl.edu | |
| Principal Investigator: Carl Pepine, MD | |
| University of Miami-Interdisciplinary Stem Cell Institute | Not yet recruiting |
| Miami, Florida, United States, 33101 | |
| Contact: Darcy Velazquez, RN, BSN 305-243-7444 DVelazqu@med.miami.edu | |
| Principal Investigator: Josh Hare, MD | |
| United States, Indiana | |
| Indiana Center for Vascular Biology and Medicine | Not yet recruiting |
| Indianapolis, Indiana, United States, 46202 | |
| Contact: Pat G'Sell 317-278-6585 pgsell@iupui.edu | |
| Contact: Judy Foltz 317-962-0531 jfoltz@iupui.edu | |
| Principal Investigator: Michael Murphy, MD | |
| United States, Kentucky | |
| University of Louisville | Not yet recruiting |
| Louisville, Kentucky, United States, 40202 | |
| Contact: Tina Collins 502-587-4106 brcoll01@louisville.edu | |
| Principal Investigator: Roberto Bolli, MD | |
| United States, Minnesota | |
| Minneapolis Heart Institute Foundation | Not yet recruiting |
| Minneapolis, Minnesota, United States, 55407 | |
| Contact: JoAnne Goldman, RT, RCIS, CCRC 612-863-3793 joanne.goldman@allina.com | |
| Principal Investigator: Tim Henry, MD | |
| United States, Texas | |
| Texas Heart Institute | Not yet recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Casey Kappenman 832-355-9054 ckappenman@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
Investigators
| Study Chair: | Robert Simari, MD | Cardiovascular Cell Therapy Research Network |
More Information
Additional Information:
Publications:
| 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: | January 18, 2013 |
| 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 Arterial Disease Intermittent Claudication Autologous Stem Cells ALDH cells Claudicants PAD |
Peak Walking Time MRI Vascular Flow Anatomy Perfusion |
Additional relevant MeSH terms:
|
Intermittent Claudication Peripheral Arterial Disease Peripheral Vascular Diseases Arteriosclerosis Arterial Occlusive Diseases |
Vascular Diseases Cardiovascular Diseases Signs and Symptoms Atherosclerosis |
ClinicalTrials.gov processed this record on May 16, 2013