Background and Aim: According to the World Health Organization, 10 million people are affected annually by traumatic brain injury (TBI), worldwide. It is a major cause of disability, being cognitive impairment the main issue that compromises quality of life. Phase II, open label studies suggested that cognitive rehabilitation therapy (CRT) might help improving cognitive performance in military personnel after TBI. However, there is no evidence that these effects are not due to placebo effect or to natural history of the disease and that are not limited to that specific population. Our proposed study will test the hypothesis that CRT improves cognitive performance of adult patients with TBI compared to a sham intervention.

Methods: This will be a randomized, sham-controlled, single-blinded with a third blinded rater, multicenter trial involving eight tertiary care hospitals in Brazil, Colombia, Germany and USA. In total, 160 patients will be stratified by TBI severity and country and randomized with concealed allocation to receive: 1) standard rehabilitation therapies + CRT or 2) standard rehabilitation therapies + sham intervention. The primary outcome is the difference in cognitive improvement compared to baseline, measured by Wechsler Memory Scale (WMS) at 12 months. The main secondary outcome is patients’ performance in Wisconsin Card Sorting Test (WCST), and Benton Visual Retention Test (BVRT) at 12 months. Other outcomes are: performance on the same tests at 6, 18 and 24 months, return to prior activity in 24 months, well-being according to WHO-5 score and functional status according to SF-36 at 12 and 24 months.

Conclusion: Cognitive impairment after TBI is a major cause of disability and requires specific rehabilitation. Currently, there are no published randomized clinical trials, with a blinding strategy, to establish the efficacy of CRT compared to a sham intervention in the recovery of TBI patients.

Key-Words: Traumatic brain injury, cognitive rehabilitation therapy, adults, cognitive scales, well-being, functional status, study protocol, study design.

Trial registration: This trial will be registered at www.clinicaltrials.gov