Testosterone replacement in hypogonadal men during inpatient rehabilitation following traumatic brain injury: Results from a double-blind, placebo-controlled clinical pilot study

Article type: Research Article

Authors: Ripley, David L.^{a; b; *} | Gerber, Don^c | Pretz, Christopher^d | Weintraub, Alan H.^c | Wierman, Margaret E.^e

Affiliations: [a] Shirley Ryan Ability Lab, Chicago, IL, USA | [b] Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA | [c] Craig Hospital, Englewood, CO, USA | [d] Lead Biostatistician, Johnson and Johnson, Irvine, CA, USA | [e] Department of Medicine, University of Colorado Anschutz Medical Campus, and Rocky Mountain Regional Veterans Affairs Research Service, Aurora, CO, USA

Correspondence: [*] Address for correspondence: David L. Ripley, MD, MS, Shirley Ryan Ability Lab, 355 East Erie Street, Chicago, IL 60611, USA. E-mail: dripley@sralab.org.

Abstract: BACKGROUND:Endocrinopathy, including hypogonadism, is common following traumatic brain injury (TBI). Prior evidence suggests hypogonadism is associated with poorer function. OBJECTIVE:Determine the feasibility, safety, and efficacy of testosterone (T) therapy in hypogonadal men following TBI in acute rehabilitation. DESIGN:Randomized, double blind, placebo-controlled pilot trial. SETTING:Inpatient rehabilitation brain injury unit. PARTICIPANTS:Men ages 18 –65, post moderate to severe TBI receiving inpatient rehabilitation. INTERVENTIONS:Transdermal T gel or placebo. MAIN OUTCOME MEASURES:Revised FIM™ score, strength, adverse events. RESULTS:Of 498 screened, 70 participants were enrolled, and 22 meeting all criteria were randomized into placebo (n = 10) or physiologic T therapy (n = 12). There was no significant difference between groups in rate of improvement on the FIM™ (intercepts t = –0.31, p = 0.7593, or slopes t = 0.61, p = 0.5472). The Treatment group demonstrated the greatest absolute improvement in FIM™ scores and grip strength compared to Placebo or Normal T groups. There was no difference in adverse events between groups. Percentage of time with agitation or aggression was highest in the Placebo group. CONCLUSIONS:Although there were no significant differences in rates of recovery, treatment group subjects showed greater absolute functional and strength improvement compared to the Placebo or Normal T groups.

Keywords: Traumatic brain injury, TBI, hypogonadism, testosterone, outcomes, function, Functional Independence Measure (FIM), strength, agitation, aggression, randomized drug trial

Keywords: Registered on ClinicalTrials.gov #NCT01201863

DOI: 10.3233/NRE-192992

Journal: NeuroRehabilitation, vol. 46, no. 3, pp. 355-368, 2020