ALD-301 for Critical Limb Ischemia, Randomized Trial

NCT00392509 | Completed Phase 1 DMC

• 1 other identifier: BB IND 12875
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Critical Limb Ischemia; Peripheral Arterial Disease; Peripheral Vascular Disease

Keywords

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

Outcome Measures

Primary Outcomes (4)

• adverse events

  6 months

• ankle-brachial systolic pressure index

  3 mo

• transcutaneous oxygen value (mm Torr)

  3 mo

• quality of life (questionnaires)

  3 mo

Secondary Outcomes (4)

• size of lower extremity ulcer(s)

  3 mo

• peripheral nerve conduction exam

  3 mo

• level of pain at rest (questionnaire)

  3 mo

• limb clinical status

  3 mo

Study Arms (1)

2

EXPERIMENTAL

Unfractionated Autologous Mononuclear Bone Marrow

Procedure: ALDH-br bone marrow cells vs. mononuclear bone marrow cells

Interventions

ALDH-br bone marrow cells vs. mononuclear bone marrow cells PROCEDURE

Surgery

2

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Aldagen: lead

Study Sites (5)

Cardiology PC

Birmingham, Alabama, 35211, United States

Location

Saint Joseph's Research Institute

Atlanta, Georgia, 30342, United States

Location

University of Indiana at Indianapolis

Indianapolis, Indiana, 46202, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Texas Heart Institute, Stem Cell Center, 6770 Bertner, St Luke's Episcopal Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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 DERIVED

Related Links

• Sponsor's Website

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia; Peripheral Arterial Disease; Peripheral Vascular Diseases

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 25, 2006
• First Posted: October 26, 2006
• Study Start: October 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: May 14, 2009

Record last verified: 2009-05

Locations

US (5)