Patients With Intermittent Claudication Injected With ALDH Bright Cells
Condition: Peripheral Artery Disease; Intermittent Claudication
MeSH terms: Peripheral Arterial Disease; Intermittent Claudication
Intervention: ALD-301; Placebo (vehicle)
Intervention description: Ten 1ml injections of ALD-301 in the index calf and posterior, lower thigh; Ten 1ml injections of placebo in the index calf and posterior, lower thigh
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 82.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Peripheral Artery Disease; Intermittent Claudication; Autologous Stem Cells; ALDH cells; Claudicants; PAD; Peak Walking Time; MRI; Vascular Flow; Anatomy; Perfusion

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.
    

Eligibility 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 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