Overview

This trial is active, not recruiting.

Conditions peripheral artery disease, intermittent claudication
Treatments ald-301, placebo (vehicle)
Phase phase 2
Sponsor The University of Texas Health Science Center, Houston
Collaborator National Heart, Lung, and Blood Institute (NHLBI)
Start date June 2013
End date August 2016
Trial size 82 participants
Trial identifier NCT01774097, HSC-SPH-12-0785, UM1HL087318-06

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Participants will receive ALD-301 via intramuscular injection
ald-301 ALDH Bright Cells
Ten 1ml injections of ALD-301 in the index calf and posterior, lower thigh
(Placebo Comparator)
Participants will receive placebo (vehicle)via intramuscular injection
placebo (vehicle) Placebo
Ten 1ml injections of placebo in the index calf and posterior, lower thigh

Primary Outcomes

Measure
Peak Walking Time (PWT)
time frame: Assessed at baseline and 6 months
Leg Collateral Count (via contrast enhanced-MR)
time frame: Assessed at baseline and 6 months
Peak Hyperemic Popliteal Flow (Phase Contrast MRA)
time frame: Assessed at baseline and 6 months
Capillary Perfusion
time frame: Assessed at baseline and 6 months

Secondary Outcomes

Measure
Pre-exercise Ankle-Brachial Index (ABI)
time frame: Assessed at baseline and 3 months
Pre-exercise Ankle-Brachial Index (ABI)
time frame: Assessed at baseline and 6 months
Post-exercise Ankle-Brachial Index (ABI)
time frame: Assessed at baseline and 3 months
Post-exercise Ankle-Brachial Index (ABI)
time frame: Assessed at baseline and 6 months
Claudication Onset Time (COT)
time frame: Assessed at baseline and 3 months
Claudication Onset Time (COT)
time frame: Assessed at baseline and 6 months
Peak Walking Time (PWT)
time frame: Assessed at baseline and 3 months
Relationship between PWT and leg collateral count
time frame: Assessed at baseline and 6 months
Relationship between PWT and peak hyperemic popliteal flow
time frame: Assessed at baseline and 6 months
Relationship between PWT and capillary perfusion
time frame: Assessed at baseline and 6 months
Walking Impairment Questionnaire (WIQ)
time frame: Assessed at baseline and 1 month
Peripheral Artery Questionnaire (PAQ)
time frame: Assessed at baseline and 1 month
Walking Impairment Questionnaire (WIQ)
time frame: Assessed at baseline and 3 months
Peripheral Artery Questionnaire (PAQ)
time frame: Assessed at baseline and 3 months
Walking Impairment Questionnaire (WIQ)
time frame: Assessed at baseline and 6 months
Peripheral Artery Questionnaire (PAQ)
time frame: Assessed at baseline and 6 months

Eligibility Criteria

Male or female participants at least 40 years old.

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 12 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 infrainguinal bypass graft in the index limb, with or without evidence of a hemodynamically significant stenosis or other defect (kinking, pseudoaneurysm, or fistula). Patients with an occluded infrainguinal bypass graft or a patent aortobifemoral or femoral-femoral bypass graft are NOT excluded. 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

Additional Information

Official title Clinical and MR Imaging Assessments in Patients With Intermittent Claudication Following Injection of Bone Marrow Derived ALDH Bright Cells
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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by The University of Texas Health Science Center, Houston.