The Safety and Efficacy Study of Autologous Concentrated Bone Marrow Aspirate (cBMA) for Critical Limb Ischemia (CLI) trial is a prospective, randomized, double-blind, placebo controlled, multicenter trial to study CLI in subjects who have no revascularization options.
The investigational treatment uses autologous cBMA at the point of care. The bone marrow aspirate is obtained from the subject’s hip, concentrated with a bone marrow concentration device, and delivered intramuscularly to the affected limb. The trial centers will use the MarrowStim PAD Kit (Biomet Biologics) to perform the procedure. Biomet Biologics has provided funding for this trial.
Vascular Disease Management spoke with trial leader Michael Murphy, MD, from the Indiana University Department of Surgery, about the therapy and details of the trial.
Q: Please describe the overall goals of the MarrowStim trial, and the patient population being studied.
A: The patient population being studied in the investigational MarrowStim Trial has severe atherosclerosis of the legs blocking most blood flow. These patients have sores, gangrene, and pain from the lack of blood flow and their only option for relief is amputation of the leg.
The primary objective of the MarrowStim Trial is to determine if intramuscular injection into the leg with the patient’s own bone marrow stem cells will improve blood flow and prevent amputation. If the MarrowStim therapy proves to be effective, it will provide an alternative treatment for this patient population whose only current option is amputation.
Q: Please describe your center’s involvement in the trial. How many centers are participating?
A: Indiana University Medical Center was the first site to enroll and treat patients in this important study and leads the nation in enrollment. At IU, we determine if a patient with CLI meets the criteria for enrollment in the study, and when a patient is enrolled they are then randomized to receiving MarrowStim or placebo. Patients enrolled in the study have a 3 out of 4 (75%) chance of receiving the MarrowStim treatment. Currently, there are 13 centers open for enrollment and the sponsor of the study continues to add new centers.
Q: How does MarrowStim work to treat PAD?
A: The subject’s own bone marrow is placed into a specialized MarrowStim device and processed to produce concentrated bone marrow aspirate, which is then injected into the subject’s affected leg. The entire procedure typically takes less than 2 hours.
Because the investigational MarrowStim Trial is currently ongoing, and because the study results are blinded, no data are currently available to make a conclusion about the treatment’s effectiveness. However, there is a growing collection of scientific literature that suggests stem cells from bone marrow may release growth factors and other signals that may stimulate development of new blood vessels and enlargement of existing blood vessels. This may result in an increase in blood flow to the leg.
Q: What results have you seen so far?
A: The results of our Phase I Safety Trial demonstrated an improvement in rest pain, quality of life, and blood flow measures at 12 weeks post treatment and a 1-year amputation-free survival rate of 86.3%. There were no reports of procedure-related deaths and two reports of procedure-related serious adverse events, neither of which was related to the MarrowStim device.
Q: Have there been any limitations or challenges in working with the treatment?
A: We have found the MarrowStim treatment is simple to use and is prepared and injected within a single procedure lasting less than 2 hours. Other stem cell treatments may require longer processing times and/or multiple procedures.
Q: What is the current status of the study, and when will it be complete?
A: The multicenter MarrowStim Trial has enrolled approximately one-third of the study subjects. We expect completion of the trial in approximately 3 years.
Q: How could this therapy affect PAD treatment in the future?
A: If MarrowStim therapy, through this investigational trial, proves to be safe and effective at preventing amputations in patients with CLI, it could potentially offer a new treatment for patients who have exhausted all surgical options and whose only remaining treatment option is amputation. An effective treatment for severe PAD could have a profound impact on the quality of life in this patient population and significantly decrease health care expenses associated with amputation.
Q: In your opinion, what is the most important message for vascular therapists to know about this treatment and the study?
A: The investigational MarrowStim Trial was the first pivotal trial of its kind in the United States for CLI. MarrowStim treatment is currently only provided at centers participating in the randomized, placebo-controlled clinical trial (listed at http://clinicaltrials.gov/ct2/show/NCT01049919). We want vascular specialists who have patients with no remaining surgical options for revascularization to know that the option is available to participate in or refer patients to this clinical trial.
Michael Murphy, MD, is a vascular surgeon and associate professor of surgery at Indiana University. Dr. Murphy reports no disclosures related to the content of this article.