Celecoxib versus placebo as an adjunct to treatment-as-usual in children and youth with obsessive-compulsive disorder: protocol for a single-site randomised quadruple-blind phase II study.

ABSTRACT

BACKGROUND: Cyclooxygenase (COX) enzymes oxidise arachidonic acid to prostaglandins, which modulate neuronal function and inflammation in the central nervous system. Consensus guidelines suggest non-steroidal anti-inflammatory drugs as a possible adjunctive approach in adults with obsessive-compulsive disorder (OCD) and in children with acute-onset OCD subtypes. However, there is limited evidence to support this approach. The primary objective of this study is to determine the efficacy of the COX-2-selective inhibitor celecoxib as an adjunct to treatment-as-usual in children and youth with moderate-to-severe OCD. The safety of this intervention including adverse events will also be systematically assessed. METHODS: The Adjunctive CElecoxib in childhood-onset OCD (ACE-OCD) study is a single-centre randomised, quadruple-blind, placebo-controlled superiority trial with two parallel groups celecoxib 100 mg twice daily and placebo. Treatments will be added to participants' routine clinical care, which will not change over the course of the study. Target recruitment is 80 participants ages 7-18 with no recent treatment changes. The primary outcome is OCD severity after 12 weeks of treatment, measured by clinician-administered Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Secondary outcomes include CY-BOCS score after 6 weeks; difference in the proportion of participants achieving a clinically meaningful response or remission; mean clinical global impression of severity and improvement after 6 and 12 weeks; and proportion of participants reporting adverse events possibly or probably related to the study intervention. The primary analyses, carried out according to intention-to-treat principles, will compare the celecoxib to placebo group on each outcome of interest, adjusting for baseline scores using analysis of covariance or logistic regression. Participants will be offered a 12-week open-label celecoxib extension and will be invited to participate in an ancillary study for biomarker analyses. ETHICS AND DISSEMINATION This protocol has been approved by the University of British Columbia Children's and Women's Research Ethics Board and has received a No Objection Letter from Health Canada. The findings will be disseminated in peer-reviewed journals and presentations to multiple stakeholders including patients, parents and healthcare providers. TRIAL REGISTRATION NUMBER NCT04673578.