CSP News: Bronx VAMC's Spinal Cord Research Unit is Awarded $12 Million Award to Study Pressure Ulcer Treatment

(3/23/2006) — The VA's Cooperative Studies Program (CSP) of the Clinical Science Research & Development Service has awarded Dr. William A. Bauman, Chairman, and Dr. Ann M. Spungen, Co-Chairperson, a $12 million award to investigate the use of anabolic steroid therapy to improve the healing of pressure ulcers in patients with spinal cord injury (SCI). Drs. Bauman and Spungen are also the Director and Associate Director of the VA's Rehabilitation Research & Development (RR&D) Service Center of Excellence for the Medical Consequences of Spinal Cord Injury and of the Spinal Cord Damage Research Center (SCDRC). Both researchers have national track records in clinical investigation of veterans with SCI.

The SCDRC was established at the Bronx VA Medical Center in 1989 by funds provided by United Spinal Association. This 5-year, multi-center award from the CSP is the largest award ever made to the Bronx research center and marks the first collaborative effort between VA's CSP and the RR&D Services and also represents the first large-scale utilization of the VA's vast clinical research potential of the SCI Services. Coincidentally, the award follows a recent decision by Congress to approve a name-change at the Bronx VAMC. The new name of the facility will honor Mr. Peters, who was most responsible for the creation of the SCDRC, as well as the flourishing of United Spinal Association and numerous other accomplishments on the local and national level. This spring, the facility will be formally re-named the James J. Peters Department of Veterans Affairs Medical Center

To date, United Spinal has provided approximately $4.5 million in research funding for the SCDRC, which is located at the Bronx VA Medical Center and administered by the Mount Sinai School of Medicine. Driven by the vision of Jim Peters, the center was created 16 years ago to study the secondary medical disabilities of persons with SCI. The investigators at this facility have made fundamental contributions to the understanding of cardiovascular disease, pulmonary dysfunction, gastrointestinal disorders, endocrinology and metabolism, energy requirements, body composition, and autonomic nervous system dysfunction in persons with SCI.

SCDRC Director Dr. Bauman said, "None of this would have been possible without Jim Peters and United Spinal Association. It couldn't have happened without their support." Associate Director Dr. Spungen explained that, due to the size of the VA's nationwide system of medical facilities, and the relative uniformity of the VA's SCI patient population, the study "permits investigators to ask and answer questions that cannot be even considered in the private sector providing healthcare to those with pressure ulcers." Bronx VA Medical Center Director of Research, Dr. Mary Sano, said the $12 million award "grew" from a 9-patient, therapeutic trial in 2000 that provided the "small kernel" of insight that led Drs. Bauman and Spungen to believe that anabolic steroids had significant potential to improve pressure ulcer healing in those with SCI. Research literature on burn treatment suggested that anabolic steroids, in conjunction with adequate calories and increased protein intake, promoted weight gain, which, in turn, was associated with burn wound closure. Eight of the 9 patients selected for the trail had non-healing pressure ulcers of 2 months to 5 years duration. The patients were treated from 1 to 12 months with oxandrolone and 8 of the 9 patients completely healed: 3 patients after 3 months; 2 patients after 4 months; 1 patient after 6 months; and 2 patients after 12 months. While the trial was not a rigorously controlled clinical investigation, the results were surprisingly positive and extremely encouraging. In February 2001, Bauman and Spungen sent a Letter of Intent to the CSP in Washington DC, proposing a multi-center, controlled clinical investigation. In November 2002, the Cooperative Studies Scientific Merit Review Board rated the proposal highly, but requested that a Feasibility Study be performed to resolve several concerns. The CSP agreed to fund this Feasibility Study for approximately $1.5 million for 1 year. After a highly successful Feasibility Study, which was presented to the Director of the CSP in September 2004, the 5-year study was approved in full this January.

The study entitled "Anabolic Steroid Therapy on Pressure Ulcer Healing in Persons with Spinal Cord Injury" (CSP No. 535), will take place at 14 VAMCs across the nation. Dr. Spungen said that they hope to enroll an average of eight patients per year for each site over the five-year study period, recruiting a total of 400 participants. The 14 participating VAMCs are: Augusta, Georgia; Bronx, New York; Cleveland, Ohio; Dallas, Texas; Hines, Illinois; Houston, Texas; Long Beach, California; Milwaukee, Wisconsin; Palo Alto, California; Richmond, Virginia; St. Louis, Missouri; San Juan, Puerto Rico; Tampa, Florida; and West Roxbury, Massachusetts.

Candidates will be selected from among the existing inpatient population at each VA Medical Center site. Prospective participants must have a Stage 3 or a Stage 4 pressure ulcer of the pelvic region. At each study site, patients will receive the "usual standards of care" and any other (adjunctive) therapy that may be of potential use to reduce the size of the ulcer. If, however, after 28 days, the ulcer has not been reduced by at least 15%, the patient will be eligible to join the Treatment Phase. Patients selected for the Treatment Phase will receive 20 mg oxandrolone, an anabolic steroid, or a placebo daily and the "usual standards of care" for 24 weeks or until complete healing of the ulcer is achieved, whichever comes first.

Dr. Spungen said the primary outcome researchers will be looking for is "a completely healed wound"––that is, full closure of the wound that stays closed for at least 96 hours.

Additional goals of the study include: proving the efficacy of oxandrolone in healing pressure ulcers; obtaining more information about the rate of healing of pressure ulcers, and about the nutritional, inflammatory and endocrine variables and their impact on healing; an economic analysis to determine the cost of care for treating pressure ulcers, and especially whether treatment costs can be reduced with the use of an anabolic steroid agent.

Anabolic steroids, such as oxandrolone, are synthetic derivatives of testosterone and promote protein synthesis, which helps build lean body tissue, including muscle. In addition to promoting weight gain, anabolic steroids have been shown to be effective for healing burns, helping children attain a more normal physical stature with delayed physical growth of Turner's syndrome, and counteracting the "wasting effect" of AIDS. Patient reaction to oxandrolone will be closely monitored by their physicians and the study personnel. Drs. Bauman and Spungen feel that the dosage and the duration of the study should pose an acceptable risk of adverse side-effects because of the potential benefit of healing a chronic pressure ulcer.

R. Ingraham (2005). Bronx VAMC's Spinal Cord Research Unit is Awarded $12 Million Award to Study Pressure Ulcer Treatment. VetsFirst, 1(3), 2005. Copyright 2005 by United Spinal Association. Reprinted with permission. www.unitedspinal.org