Patients With Intermittent Claudication Injected With ALDH Bright Cells

NCT01774097 | Completed Phase 2 Results DMC

• 2 other identifiers: HSC-SPH-12-0785UM1HL087318-06
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 9

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.

Conditions

Peripheral Artery Disease; Intermittent Claudication

Keywords

Peripheral Artery Disease; Intermittent Claudication; Autologous Stem Cells; ALDH cells; Claudicants; PAD; Peak Walking Time; MRI; Vascular Flow; Anatomy; Perfusion

Outcome Measures

Primary Outcomes (4)

• Peak Walking Time (PWT)

  The placebo adjusted average change over time in the maximum time (in minutes) 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.

  Assessed at baseline and 6 months

• Leg Collateral Count (Via Contrast Enhanced-MR)

  The placebo adjusted average change in the number of collateral vessels over time.

  Assessed at baseline and 6 months

• Peak Hyperemic Popliteal Flow (Phase Contrast MRA)

  The placebo adjusted average change in peak hyperemic popliteal flow (mL/s) over time.

  Assessed at baseline and 6 months

• Capillary Perfusion

  The placebo adjusted average change in capillary perfusion over time.

  Assessed at baseline and 6 months

Secondary Outcomes (8)

• Pre-exercise Ankle-Brachial Index (ABI)

  Assessed as a trajectory (baseline, 3mos, and 6 mos)

• Post-exercise Ankle-Brachial Index (ABI)

  Assessed as a trajectory (baseline, 3mos, and 6 mos)

• Claudication Onset Time (COT)

  Assessed as a trajectory (baseline, 3mos, and 6 mos)

• Peak Walking Time (PWT)

  Assessed at baseline and 3 months

• Peripheral Artery Questionnaire (PAQ)

  Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos)

Study Arms (2)

ALD-301

EXPERIMENTAL

Participants will receive ALD-301 via intramuscular injection

Biological: ALD-301

Placebo (vehicle)

PLACEBO COMPARATOR

Participants will receive placebo (vehicle)via intramuscular injection

Biological: Placebo (vehicle)

Interventions

ALD-301 BIOLOGICAL

Ten 1ml injections of ALD-301 in the index calf and posterior, lower thigh

Also known as: ALDH Bright Cells, ALDHbr, Aldehyde dehydrogenase-bright cells

ALD-301

Placebo (vehicle) BIOLOGICAL

Ten 1ml injections of placebo in the index calf and posterior, lower thigh

Also known as: Placebo, Vehicle, HSA, Human Serum Albumin

Placebo (vehicle)

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age ≥40 years
• Resting ankle-brachial index \<0.90 or a resting toe-brachial index of \<0.70 at baseline testing
• 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.

You may not qualify if:

• 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 12 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 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.
• 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 Disease
• 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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Aldagen: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (9)

Stanford University School of Medicine (Falk Cardiovascular Research Center)

Stanford, California, 94305, United States

Location

University of Florida-Department of Medicine

Gainesville, Florida, 32610, United States

Location

University of Miami-Interdisciplinary Stem Cell Institute

Miami, Florida, 33101, United States

Location

Orlando Health Inc.

Orlando, Florida, 32806, United States

Location

Indiana Center for Vascular Biology and Medicine

Indianapolis, Indiana, 46202, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407, United States

Location

Clinical and Translational Science Institute at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Texas Heart Institute

Houston, Texas, 77030, United States

Location

Related Publications (4)

• 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. doi: 10.1161/CIRCULATIONAHA.106.174526. No abstract available.

  PMID: 16549646 BACKGROUND

• 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.

  PMID: 21594960 BACKGROUND

• Perin EC, Murphy M, Cooke JP, Moye L, Henry TD, Bettencourt J, Gahremanpour A, Leeper N, Anderson RD, Hiatt WR, Lima JA, Venkatesh B, Sayre SL, Vojvodic RW, Taylor DA, Ebert RF, Hirsch AT; Cardiovascular Cell Therapy Research Network. Rationale and design for PACE: patients with intermittent claudication injected with ALDH bright cells. Am Heart J. 2014 Nov;168(5):667-73. doi: 10.1016/j.ahj.2014.07.021. Epub 2014 Jul 30.

  PMID: 25440794 BACKGROUND

• Perin EC, Murphy MP, March KL, Bolli R, Loughran J, Yang PC, Leeper NJ, Dalman RL, Alexander J, Henry TD, Traverse JH, Pepine CJ, Anderson RD, Berceli S, Willerson JT, Muthupillai R, Gahremanpour A, Raveendran G, Velasquez O, Hare JM, Hernandez Schulman I, Kasi VS, Hiatt WR, Ambale-Venkatesh B, Lima JA, Taylor DA, Resende M, Gee AP, Durett AG, Bloom J, Richman S, G'Sell P, Williams S, Khan F, Gyang Ross E, Santoso MR, Goldman J, Leach D, Handberg E, Cheong B, Piece N, DiFede D, Bruhn-Ding B, Caldwell E, Bettencourt J, Lai D, Piller L, Simpson L, Cohen M, Sayre SL, Vojvodic RW, Moye L, Ebert RF, Simari RD, Hirsch AT; Cardiovascular Cell Therapy Research Network (CCTRN). Evaluation of Cell Therapy on Exercise Performance and Limb Perfusion in Peripheral Artery Disease: The CCTRN PACE Trial (Patients With Intermittent Claudication Injected With ALDH Bright Cells). Circulation. 2017 Apr 11;135(15):1417-1428. doi: 10.1161/CIRCULATIONAHA.116.025707. Epub 2017 Feb 16.

  PMID: 28209728 DERIVED

Related Links

• Cardiovascular Cell Therapy Research Network
• National Heart, Lung, and Blood Institute

MeSH Terms

Conditions

Peripheral Arterial Disease; Intermittent Claudication

Interventions

Serum Albumin, Human

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Serum Albumin; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Blood Proteins

Limitations and Caveats

Small sample size. Only follow up to 6 months. Limitation in the cell dose.

Results Point of Contact

• Title: Lemuel Moye, MD, PhD
• Organization: UT-Houston School of Public Health

lemmoye@msn.com

713-500-9518

Study Officials

• Robert Simari, MD

  Cardiovascular Cell Therapy Research Network

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor - School of Public Health

Study Record Dates

• First Submitted: January 18, 2013
• First Posted: January 23, 2013
• Study Start: June 1, 2013
• Primary Completion: August 1, 2016
• Study Completion: March 1, 2017
• Last Updated: April 21, 2017
• Results First Posted: April 21, 2017

Record last verified: 2017-03

Locations

US (9)