Peripheral Artery DiseasePhase 2PACENCT01774097

Patients With Intermittent Claudication Injected With ALDH Bright Cells

A Phase 2 study testing ALD-301 in people with Peripheral Artery Disease and Intermittent Claudication, run by The University of Texas Health Science Center, Houston at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 40 years and older
Conditions the study is for: Peripheral Artery Disease, Intermittent Claudication
What is being tested?: ALD-301
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 82 participants
Where: 9 sitesUnited States
Study dates: Jun 2013to Mar 2017
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Show all 26Show fewer

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
Contraindication to magnetic resonance imaging (MRI) (including knee/tibial/fibular replacement hardware in the index leg) 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]
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
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

Trial locations and contacts

9 sites in 1 country.

City, postcode or hospital

9 sites in 1 country

United States9 sites

University of Florida-Department of Medicine
Gainesville, Florida, 32610
Texas Heart Institute
Houston, Texas, 77030
Indiana Center for Vascular Biology and Medicine
Indianapolis, Indiana, 46202
University of Louisville
Louisville, Kentucky, 40202
University of Miami-Interdisciplinary Stem Cell Institute
Miami, Florida, 33101
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, 55407
Clinical and Translational Science Institute at University of Minnesota
Minneapolis, Minnesota, 55455
Orlando Health Inc.
Orlando, Florida, 32806
Stanford University School of Medicine (Falk Cardiovascular Research Center)
Stanford, California, 94305

Other trials in United States

About this study

Official title: Clinical and MR Imaging Assessments in Patients With Intermittent Claudication Following Injection of Bone Marrow Derived ALDH Bright Cells

Read the detailed 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.

Conditions: Peripheral Artery Disease, Intermittent Claudication
Being tested: ALD-301, Placebo (vehicle)
Keywords: Peripheral Artery Disease, Intermittent Claudication, Autologous Stem Cells, ALDH cells, Claudicants, PAD, Peak Walking Time, MRI, Vascular Flow, Anatomy, Perfusion
Medical subject headings: Peripheral Arterial Disease, Intermittent Claudication

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ALD-301Biological
Also called ALDH Bright Cells, ALDHbr, Aldehyde dehydrogenase-bright cells
Ten 1ml injections of ALD-301 in the index calf and posterior, lower thigh
Placebo (vehicle)Biological
Also called Placebo, Vehicle, HSA, Human Serum Albumin
Ten 1ml injections of placebo in the index calf and posterior, lower thigh

Study groups in NCT01774097
Study group	Role	What they receive
ALD-301	Experimental	Participants will receive ALD-301 via intramuscular injection Receives: Biological: ALD-301
Placebo (vehicle)	Placebo comparator	Participants will receive placebo (vehicle)via intramuscular injection Receives: Biological: Placebo (vehicle)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: Assessed at baseline and 6 months
Capillary Perfusion
The placebo adjusted average change in capillary perfusion over time.
Measured: Assessed at baseline and 6 months

Secondary outcomes (8)

Pre-exercise Ankle-Brachial Index (ABI)
ABI is the ratio of the blood pressure at the ankle to the blood pressure of the upper arm. Pre-exercise ABI is collected routinely with the patient supine immediately prior to a treadmill test. This measure represents the placebo adjusted average change over time in arm and pedal (ankle) blood pressure. The reported value is the estimate from regression analysis of the slope of the placebo adjusted measure over the time course of the trial adjusted for baseline weight.
Measured: Assessed as a trajectory (baseline, 3mos, and 6 mos)
Post-exercise Ankle-Brachial Index (ABI)
ABI is the ratio of the blood pressure at the ankle to the blood pressure of the upper arm. Post-exercise ABI is collected routinely with the patient supine immediately following a treadmill test. This measure represents the placebo adjusted average change over time in arm and pedal (ankle) blood pressure. The reported value is the estimate from regression analysis of the slope of the placebo adjusted measure over the time course of the trial adjusted for baseline weight.
Measured: Assessed as a trajectory (baseline, 3mos, and 6 mos)
Claudication Onset Time (COT)
Claudication Onset Time (COT) is the walking time at which patients first experience leg pain during a treadmill test. The measure represents placebo adjusted average change over time (in minutes) 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. The reported value is the estimate from regression analysis of the slope of the placebo adjusted measure over the time course of the trial adjusted for baseline weight.
Measured: Assessed as a trajectory (baseline, 3mos, and 6 mos)
Peak Walking Time (PWT)
The average change in 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.
Measured: Assessed at baseline and 3 months
Peripheral Artery Questionnaire (PAQ)
The Peripheral Artery Questionnaire (PAQ) assesses subjective physical limitations, leg symptoms, social function, treatment satisfaction, and quality of life. It is administered as a self report. Higher scores are indicative of better outcome. The summary scores is compiled by taking the mean of five subscales generated from the original questions. Range: Minimum score is 11.1, maximum 85. The measure represents placebo adjusted average change in Peripheral Artery Questionnaire (PAQ) summary score assessed over time. The reported value is the estimate from regression analysis of the slope of the placebo adjusted measure over the time course of the trial adjusted for baseline weight.
Measured: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos)
Walking Impairment Questionnaire (WIQ)-Walking Distance Score
The Walking Impairment Questionnaire (WIQ) assesses the severity of the subjective walking impairment on distance, speed, and stair climbing scales. It is administered as a self report. Range: Minimum score is 0.2, maximum 100. The measure represents the placebo adjusted average change in WIQ walking distance score assessed over time. The reported value is the estimate from regression analysis of the slope of the placebo adjusted measure over the time course of the trial adjusted for baseline weight.
Measured: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos)
Walking Impairment Questionnaire (WIQ)- Walking Speed Score
The Walking Impairment Questionnaire (WIQ) assesses the severity of the subjective walking impairment on distance, speed, and stair climbing scales. It is administered as a self report. Range: Minimum score is 0, maximum 87. The measure represents the placebo adjusted average change in WIQ walking speed score assessed over time. The reported value is the estimate from regression analysis of the slope of the placebo adjusted measure over the time course of the trial adjusted for baseline weight.
Measured: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos)
Walking Impairment Questionnaire (WIQ)-Ability to Climb Stairs Score
The Walking Impairment Questionnaire (WIQ) assesses the severity of the subjective walking impairment on distance, speed, and stair climbing scales. It is administered as a self report. Range: Minimum score is 0, maximum 100. The measure represents the placebo adjusted average change in WIQ ability to climb stairs score assessed over time. The reported value is the estimate from regression analysis of the slope of the placebo adjusted measure over the time course of the trial adjusted for baseline weight.
Measured: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2013Mar 2017

First posted23 Jan 2013 (estimated)
Study startJun 2013
Primary completionAug 2016
Study completionMar 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Peripheral Artery DiseaseStudies of the same condition, open and under way.
More trials run by The University of Texas Health Science Center, HoustonThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 82 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01774097
Sponsor's protocol ID: HSC-SPH-12-0785
Other IDs: UM1HL087318-06
Acronym: PACE
Status last verified: Mar 2017
First submitted: 18 Jan 2013
Last updated: 21 Apr 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 16549646
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.
PubMed 21594960
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.
PubMed 25440794
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.
PubMed 28209728

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 21 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Clinical and MR Imaging Assessments in Patients With Intermittent Claudication Following Injection of Bone Marrow Derived ALDH Bright Cells
ClinicalTrials.gov ID: NCT01774097
Acronym / sponsor ID: PACE / HSC-SPH-12-0785
Conditions: Peripheral Artery Disease, Intermittent Claudication
Keywords: Peripheral Artery Disease, Intermittent Claudication, Autologous Stem Cells, ALDH cells, Claudicants, PAD, Peak Walking Time, MRI
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 82 participants (actual)
Lead sponsor: The University of Texas Health Science Center, HoustonUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI), Aldagen, Center for Cell and Gene Therapy, Baylor College of Medicine
Study start: Jun 2013 (actual)
Primary completion: Aug 2016 (actual)
Study completion: Mar 2017 (actual)
First posted: 23 Jan 2013 (estimated)
Results: Posted 21 Apr 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
ALD-301	Experimental	Biological: ALD-301Participants will receive ALD-301 via intramuscular injection
Placebo (vehicle)	Placebo comparator	Biological: Placebo (vehicle)Participants will receive placebo (vehicle)via intramuscular injection

Who may qualify

Ages: 40 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (26 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ALD-301Also: ALDH Bright Cells, ALDHbr, Aldehyde dehydrogenase-bright cellsTen 1ml injections of ALD-301 in the index calf and posterior, lower thigh	Biological	ALD-301
Placebo (vehicle)Also: Placebo, Vehicle, HSA, Human Serum AlbuminTen 1ml injections of placebo in the index calf and posterior, lower thigh	Biological	Placebo (vehicle)

Primary outcome

Peak Walking Time (PWT)
Time frame: Assessed at baseline and 6 months
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.
Leg Collateral Count (Via Contrast Enhanced-MR)
Time frame: Assessed at baseline and 6 months
The placebo adjusted average change in the number of collateral vessels over time.
Peak Hyperemic Popliteal Flow (Phase Contrast MRA)
Time frame: Assessed at baseline and 6 months
The placebo adjusted average change in peak hyperemic popliteal flow (mL/s) over time.
Capillary Perfusion
Time frame: Assessed at baseline and 6 months
The placebo adjusted average change in capillary perfusion over time.

8 secondary outcomes

Pre-exercise Ankle-Brachial Index (ABI)
Time frame: Assessed as a trajectory (baseline, 3mos, and 6 mos)
Post-exercise Ankle-Brachial Index (ABI)
Time frame: Assessed as a trajectory (baseline, 3mos, and 6 mos)
Claudication Onset Time (COT)
Time frame: Assessed as a trajectory (baseline, 3mos, and 6 mos)
Peak Walking Time (PWT)
Time frame: Assessed at baseline and 3 months
Peripheral Artery Questionnaire (PAQ)
Time frame: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos)
Walking Impairment Questionnaire (WIQ)-Walking Distance Score
Time frame: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos)
Walking Impairment Questionnaire (WIQ)- Walking Speed Score
Time frame: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos)
Walking Impairment Questionnaire (WIQ)-Ability to Climb Stairs Score
Time frame: Assessed as a trajectory (baseline, 1mos, 3mos, and 6 mos)

Results and safety

Results posted to the registry on 21 Apr 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ALDHbr	40	38
Placebo (Vehicle)	42	40

Primary outcome: Peak Walking Time (PWT)

Time frame: Assessed at baseline and 6 months. Mean (Standard Deviation). Unit: minutes

Measure	ALDHbr n = 37	Placebo (Vehicle) n = 39
Value	2.2 (3.9)	1.2 (2.7)

ALDHbr vs Placebo (Vehicle): Mean Difference (Net): 0.9 (95% CI -0.6 to 2.5), p = 0.238, t-test, 2 sided

Population analysed: Participants who had available analyzable baseline and 6 month treadmill test results.

Primary outcome: Leg Collateral Count (Via Contrast Enhanced-MR)

Time frame: Assessed at baseline and 6 months. Mean (Standard Deviation). Unit: vessel count

Measure	ALDHbr n = 37	Placebo (Vehicle) n = 38
Value	1.5 (2.7)	0.6 (2.2)

ALDHbr vs Placebo (Vehicle): Mean Difference (Net): 0.9 (95% CI -0.2 to 2.1), p = 0.116, t-test, 2 sided

Population analysed: Participants who had available analyzable baseline and 6 month MRI imaging

Primary outcome: Peak Hyperemic Popliteal Flow (Phase Contrast MRA)

Time frame: Assessed at baseline and 6 months. Mean (Standard Deviation). Unit: ml/sec

Measure	ALDHbr n = 35	Placebo (Vehicle) n = 36
Value	0.2 (1.5)	0.2 (1.9)

ALDHbr vs Placebo (Vehicle): Mean Difference (Net): 0.0 (95% CI -0.8 to 0.8), p = 0.978, t-test, 2 sided

Population analysed: Participants who had available analyzable baseline and 6 month MRI imaging

Primary outcome: Capillary Perfusion

Time frame: Assessed at baseline and 6 months. Mean (Standard Deviation). Unit: percent

Measure	ALDHbr n = 38	Placebo (Vehicle) n = 38
Value	-0.42 (2.40)	-0.25 (2.36)

ALDHbr vs Placebo (Vehicle): Mean Difference (Net): -0.17 (95% CI -1.26 to 0.91), p = 0.752, t-test, 2 sided

Population analysed: Participants with available analyzable MRI imaging at baseline and 6 months

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Events reported are from randomization date to the 6 month endpoint data collection window (i.e 210 days post intervention). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ALDHbr	4 of 40 (10%)	1 of 40 (2.5%)	Not reported
Placebo (Vehicle)	8 of 42 (19%)	6 of 42 (14.3%)	Not reported

Limitations and caveats (from the sponsor): Small sample size. Only follow up to 6 months. Limitation in the cell dose.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 16549646Hirsch 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.
Background: PubMed 21594960Perin 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.
Background: PubMed 25440794Perin 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.
Derived from this study: PubMed 28209728Perin 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.
Cardiovascular Cell Therapy Research NetworkLink provided by the sponsor.
National Heart, Lung, and Blood InstituteLink provided by the sponsor.

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Peripheral Arterial Disease

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Robert Simari, MD study chair

Cardiovascular Cell Therapy Research Network

9 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ALD-301 in people with Peripheral Artery Disease and Intermittent Claudication, run by The University of Texas Health Science Center, Houston at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Peak Walking Time (PWT) (time frame: Assessed at baseline and 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01774097, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2017.