Introduction The approved analgesic and anti-inflammatory drugs ibuprofen and
indometacin block the small GTPase RhoA, a key enzyme that impedes axonal
sprouting after axonal damage. Inhibition of the Rho pathway in a central
nervous system-effective manner requires higher dosages compared with orthodox
cyclooxygenase-blocking effects. Preclinical studies on spinal cord injury
(SCI) imply improved motor recovery after ibuprofen/indometacin-mediated Rho
inhibition. This has been reassessed by a meta-analysis of the underlying
experimental evidence, which indicates an overall effect size of 20.2%
regarding motor outcome achieved after ibuprofen/indometacin treatment
compared with vehicle controls. In addition, ibuprofen/indometacin may also
limit sickness behaviour, non-neurogenic systemic inflammatory response
syndrome (SIRS), neuropathic pain and heterotopic ossifications after SCI.
Consequently, ‘small molecule’-mediated Rho inhibition after acute SCI
warrants clinical investigation. Methods and analysis Protocol of an
investigator-initiated clinical open-label pilot trial on high-dose ibuprofen
treatment after acute traumatic, motor-complete SCI. A sample of n=12 patients
will be enrolled in two cohorts treated with 2400 mg/day ibuprofen for 4 or 12
weeks, respectively. The primary safety end point is an occurrence of serious
adverse events, primarily gastroduodenal bleedings. Secondary end points are
pharmacokinetics, feasibility and preliminary effects on neurological
recovery, neuropathic pain and heterotopic ossifications. The primary safety
analysis is based on the incidence of severe gastrointestinal bleedings.
Additional analyses will be mainly descriptive and casuistic. Ethics and
dissemination The clinical trial protocol was approved by the responsible
German state Ethics Board, and the Federal Institute for Drugs and Medical
Devices. The study complies with the Declaration of Helsinki, the principles
of Good Clinical Practice and all further applicable regulations. This safety
and pharmacokinetics trial informs the planning of a subsequent randomised
controlled trial. Regardless of the result of the primary and secondary
outcome assessments, the clinical trial will be reported as a publication in a
peer-reviewed journal. Trial registration number NCT02096913; Pre-results
