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ALD-301 for Critical Limb Ischemia, Randomized Trial (CLI-001)
This study is currently recruiting participants.
Verified by Aldagen, April 2008
First Received: October 25, 2006   Last Updated: April 2, 2008   History of Changes
Sponsored by: Aldagen
Information provided by: Aldagen
ClinicalTrials.gov Identifier: NCT00392509
  Purpose

This study will treat patients with such severe lower leg ischemia or vascular compromise that they have pain at rest. The goal is to compare treatment of the patient's painful disorder by injecting cells into the calf of the leg and testing for circulatory improvement. A treatment will given at random to two groups and will be injection into the calf muscle with ALD-301 (specially processed stem and progenitor cells) from the patient's own bone marrow, or with cells processed by more routine that minimally purifies the cells. The study goal is to see if the ALD-301 cells are more effective in generating new small blood vessels to improve the circulation to the affected leg.


Condition Intervention Phase
Critical Limb Ischemia
Peripheral Arterial Disease
Peripheral Vascular Disease
Procedure: ALDH-br bone marrow cells vs. mononuclear bone marrow cells
Phase I
Phase II

MedlinePlus related topics: Peripheral Arterial Disease Vascular Diseases
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title: A Phase I-II Randomized Autologous Bone Marrow Derived Aldehyde Dehydrogenase-Bright (ALDHbr) Cells Against Unfractionated Autologous Mononuclear Bone Marrow in Patients With Rutherford 4 or 5 Peripheral Arterial Occlusive Disease

Further study details as provided by Aldagen:

Primary Outcome Measures:
  • adverse events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • ankle-brachial systolic pressure index [ Time Frame: 3 mo ] [ Designated as safety issue: No ]
  • transcutaneous oxygen value (mm Torr) [ Time Frame: 3 mo ] [ Designated as safety issue: No ]
  • quality of life (questionnaires) [ Time Frame: 3 mo ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • size of lower extremity ulcer(s) [ Time Frame: 3 mo ] [ Designated as safety issue: No ]
  • peripheral nerve conduction exam [ Time Frame: 3 mo ] [ Designated as safety issue: No ]
  • level of pain at rest (questionnaire) [ Time Frame: 3 mo ] [ Designated as safety issue: No ]
  • limb clinical status [ Time Frame: 3 mo ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: October 2006
Estimated Study Completion Date: October 2008
Estimated Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
2: Experimental
Unfractionated Autologous Mononuclear Bone Marrow
Procedure: ALDH-br bone marrow cells vs. mononuclear bone marrow cells
Surgery

Detailed Description:

Patients will be recruited who have critical limb ischemia with pain at rest. The study will select patients for treatment and follow them for three months after intervention. The treatment will consist of drawing about 2/3 of a cup of bone marrow from the patient's hip bone, then processing the collected bone marrow will be as follows:

  • The test group's bone marrow will be processed and sorted to identify the aldehyde dehydrogenase bright ALDH-br stem and progenitor cells (ALD-301).

These cells will be injected into the calf muscle of the patient in clinic.

  • The control group will have the same amount of bone marrow collected but it will undergo a simpler process to isolate the mononuclear cells from the whole bone marrow, removing most of the red cells and granulocytes from cell preparation for injection.

The patients will be monitored for adverse events related to this process to determine the safety of the approach. They will also be tested at intervals during the study to compare baseline values of each patient with the post-treatment values of:

  1. ankle-brachial index of systolic blood pressure
  2. the transcutaneous oxygen measurements obtained from the skin of the treated leg
  3. the patient's perception of his/her quality of life as measured by two different, validated questionnaires
  4. Measurements of of heel/foot ulcers, if present, to monitor degree of healing if it occurs
  5. the patient's perception of his/her level of pain in the leg

The patients will receive a call at 6 months to report on additional life events following the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients 18 years of age or greater with atherosclerotic vascular disease that is viewed as not readily amenable to reconstructive surgery and Rutherford Category 4 ischemia (ischemic rest pain) and Rutherford Category 5 ischemia (ulceration or tissue necrosis) and by the judgment of their referring physician are not reasonable candidates for revascularization options of either percutaneous balloon angioplasty or a surgical revascularization.
  • Objective evidence of severe peripheral arterial disease will include an ankle brachial index (ABI) of less than 0.5, or, in the case of patients who have vessels calcified and thereby "non-compressible" vessels metatarsal pulse volume recording (PVR) that is flat or barely pulsatile in the diseased limb on two consecutive examinations performed at least one week apart.
  • Patients competent to give informed consent.
  • No active malignant disease that could involve the bone marrow, or history of treatment of malignant disease that could have damaged the bone marrow.
  • Before being accepted for the study the patient must be screened for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, human transmissible spongiform encephalopathy, including Creutzfeldt-Jacob Disease, Treponema pallidum, and have a negative standard infectious disease panel including a CMV PCR test.
  • Patients who are hemodynamically stable.

Exclusion Criteria:

  • Patients with poorly controlled diabetes mellitus (HbA1C > 8%)
  • Patients with renal insufficiency (creatinine > 2.5).
  • Patients with evidence of infectious disease as determined by e. above or other medical findings.
  • Pregnant women (women capable of childbearing must have a negative pregnancy test).
  • Patients with cognitive impairments.
  • Other comorbid disease that would be expected to result in less than one year life expectancy
  • Past malignancy or history of chemotherapy or radiation affecting the bone marrow.
  • History of inflammatory or progressively fibrotic conditions: .e.g., rheumatoid arthritis, systemic lupus erythematosis, vasculitic disorders, idiopathic pulmonary fibrosis, retroperitoneal fibrosis
  • Infection as evidenced by WBC count of >15,000 and/or temperature >38 degrees C. Large area of cellulitis in the afflicted limb that in the opinion of the investigators would require the institution of antibiotics OR evidence of osteomyelitis corroborated by radiographic or scintigraphic examination
  • Cardiovascular conditions:

    • Exercise limiting angina ( Canadian Cardiovascular Society Class 3 (Appendix 7);
    • Congestive heart failure (New York Heart Association class 3 (Appendix 5);
    • Unstable angina;
    • Acute ST elevation myocardial infarction (MI) within 1month;
    • Transient ischemic attack or stroke within 1 month;
    • Severe valvular disease
  • Patients with any history of organ transplants;
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00392509

Contacts
Contact: Rachael Crozier, RN, MS 919 484-2571 ext 260 rcrozier@aldagen.com

Locations
United States, Alabama
Cardiology PC Recruiting
Birmingham, Alabama, United States, 35211
Contact: Susan DeRamus, RN     205-780-4330 ext 338     SDeramus@cardiologypc.com    
Principal Investigator: Farrell Mendelsohn, MD            
United States, Georgia
Saint Joseph's Research Institute Recruiting
Atlanta, Georgia, United States, 30342
Contact: Nichelle Jackson, RN     404-843-6089     nljackson@sjha.org    
Contact: Ioana Ghiu, MD, MS     404 843-6078     ighiu@sjha.org    
Principal Investigator: Nicolas Chronos, MD            
United States, Indiana
University of Indiana at Indianapolis Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Janet Klein, RN, MSN     317-962-0287     jswklein@iupui.edu    
Principal Investigator: Michael Murphy, M.D.            
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Kim McIntosh     919-681-5072     kim.mcintosh@duke.edu    
Principal Investigator: Robert Mitchell, M.D.            
United States, Texas
Texas Heart Institute, Stem Cell Center, 6770 Bertner, St Luke's Episcopal Hospital Recruiting
Houston,, Texas, United States, 77030
Contact: Sandi Shaw, RN     832-355-9802     sshaw@heart.thi.tmc.edu    
Contact: Deirdre Smith, RN     832 355-9801     dxsmith@heart.thi.tmc.edu    
Principal Investigator: Emerson C Perin, M.D., Ph.D.            
Sponsors and Collaborators
Aldagen
Investigators
Principal Investigator: Emerson C Perin, M.D., Ph.D. Stem Cell Center, Texas Heart Institute, St Luke's Episcopal Hospital, 6770 Bertner , Suite 1020 Texas Medical Center,Houston, Texas 77030
Principal Investigator: Robert Mitchell, MD Duke University
Principal Investigator: Michael Murphy, MD University of Indiana at Indianapolis
Principal Investigator: Nicolas Chronos, MD Saint Joseph's Research Institute
Principal Investigator: Farrell Mendelsohn, MD Cardiology PC
  More Information

Additional Information:
No publications provided

Responsible Party: Aldagen, Inc. ( Laurence Keller, MD )
Study ID Numbers: BB IND 12875
Study First Received: October 25, 2006
Last Updated: April 2, 2008
ClinicalTrials.gov Identifier: NCT00392509     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Aldagen:
critical limb ischemia
cell therapy for angiogenesis
aldehyde dehydrogenase-bright cells
peripheral artery disease
peripheral vascular disease
leg pain
PVD
PAD
CLI
amputation
limb salvage

Study placed in the following topic categories:
Arterial Occlusive Diseases
Peripheral Vascular Diseases
Vascular Diseases
Pain
Ischemia

Additional relevant MeSH terms:
Arterial Occlusive Diseases
Pathologic Processes
Peripheral Vascular Diseases
Vascular Diseases
Cardiovascular Diseases
Ischemia

ClinicalTrials.gov processed this record on May 07, 2009