Project D2:  Effect of an oral anabolic steroid on pulmonary function and body composition in individuals with chronic spinal cord injury: a pilot study

Principal Investigators:  Suzanne Groah, MD, MSPH, Lauro S. Halsead, MD, MPH
Co-investigator:   Larry Hamm, PhD

Funding Source: Neuroscience Research Center (USAMRMC)

Abstract:
Oxandrolone, a derivative of testosterone, is an oral anabolic steroid with a large anabolic to androgenic potential. It is approved by the Food and Drug Administration (FDA) as an adjunctive therapy to promote weight gain (lean body mass) following extensive surgery, chronic infections, or severe trauma, and in some patients who without definite pathophysiologic reasons fail to gain or maintain normal weight.

Oxandrolone has been used in the non-spinal injured with human immunodeficiency virus (HIV), cancer-associated cachexia, and chronic obstructive pulmonary disease (COPD) to successfully combat nitrogen wasting and lean muscle loss. More recently, oxandrolone has been used as an adjunct in non-healing pressure wounds.

The individual with acute spinal cord injury (SCI) undergoes a severe catabolic phase characterized by nitrogen wasting and loss of lean body mass. With time and inactivity associated with the SCI, significant changes in body composition occur, with an increase in fat mass and a decrease in muscle mass. This change in body composition is likely one contributing factor for the increasing incidence of cardiovascular disease and diabetes seen with spinal injured individuals who are surviving to older ages.

Additionally, most individuals with an SCI incur some degree of pulmonary insufficiency due to the neurologic impairment. Pulmonary complications such as pneumonia and atelecatasis are responsible for most deaths immediately after SCI and in long-term SCI. Further, pulmonary complications are the 2nd leading cause of morbidity after SCI.

In individuals with SCI, oxandrolone has the potential to improve several comorbidities that have short-, and long-term implications. Preliminary results from an ongoing research trial show that diaphragm girth measurements increase after a course of oxandrolone in subjects with SCI. This correlates with results from previous studies showing that individuals with chronic SCI can have improvements in their pulmonary spirometry values and report less dyspnea after a course of oxandrolone therapy. The primary investigator of this study has used oxandrolone in patients with SCI as an adjunct for pressure wound healing. It was noted in those patients that pulmonary function improved above and beyond what would be expected.

The changes in body composition that occur after SCI, characterized by increased fat mass and decreased muscle mass is well-documented. Also, the beneficial effect of oxandolone on body composition is well-documented in the non-SCI population. Therefore, it would be expected that SCI is another condition for which oxandrolone may significantly improve body composition, and thus diminish the sequelae associated with changes in body composition.

Tonalin CLA (conjugated linoleic acid) is part of a group of polyunsaturated fatty acids found in animal meat, dairy products and other natural sources. It has been shown to decrease body fat mass. The purpose of this pilot project is to determine whether oxandrolone, CLA, or both improve body composition and pulmonary function in individuals with chronic spinal cord injury (SCI).  Individuals with C8 ASIA A or B or higher SCI of at least 1 year will be randomized to either the Oxandrolone, CLA, or Control groups. All participants will receive baseline liver function tests (LFTs), lipid panel, pulmonary function testing (PFTs) and dual x-ray absorptiometry (DEXA) for body composition analysis. Subjects will then receive either 8 weeks of oxandrolone, CLA, or neither. Participants will then have laboratory studies including lipid panel, LFTs, PFTs, and DEXA immediately after the intervention period and then 3 months later to determine if any changes are maintained.

The effect of improvements in body composition could be far-reaching, with a decreased risk of pressure ulcers, diabetes mellitus, and cardiovasular disease. Likewise, if we can strengthen pulmonary muscles, it is likely the individuals risk of pneumonia and atelectasis will decline. This would have a significant positive impact on the rate of rehospitalization, morbidity, quality of life, and mortality.