Protocol for olfactory training in persisting COVID-19-associated loss of smell (SMELL): a monocentric randomised controlled trial conducted in Innsbruck

Abstract

Introduction: Olfactory dysfunction (OD) following COVID-19 affected up to 70% of patients, with more than 30% still reporting lingering symptoms a year later. Treatment is essential, as previous research has linked (postviral) OD to depression, impaired quality of life (QoL) and even heightened mortality rates.

Methods and analysis: We designed a monocentric, single-blinded randomised controlled trial evaluating the efficacy of olfactory training (OT) in individuals with persisting COVID-19-associated loss of smell. Randomisation will be done in a 1:1 manner. OT will be performed using the Sniffin' Sticks Duft Quartett over a period of 12 weeks, two times per day. The primary endpoint of this study is the change in olfactory score between baseline and after 12 weeks, measured by the combined score of the identification and discrimination subscales of the Sniffin' Sticks testing battery. QoL, overall health, mood, personal well-being and symptom severity will be assessed at baseline and during a follow-up visit, using multiple validated questionnaires and scales. OT is offered to the second cohort during an open-label phase extension. This manuscript highlights and discusses the study protocol.

Ethics and dissemination: Ethical approval for the study was obtained from the Ethics Commission of the Medical University of Innsbruck, Austria. Results of this study will be shared through conferences and publications in peer-reviewed journals.

Trial registration number: NCT05421221.

Keywords: COVID-19; Quality of Life; Randomized Controlled Trial.

Figure 1. The SMELL trial includes a maximum of three in-person visits, depending on the cohort assignment. All participants are screened at a baseline visit for inclusion and exclusion criteria, and written ICF will be obtained. They are randomised in a 1:1 fashion, with group 1 (training cohort) conducting OT for the following 12 weeks. All participants will complete a second visit (final visit), which takes place 12 weeks after the initial baseline visit. The primary endpoints are reached at this point. The study ends here for the first cohort, though the second cohort is offered OT in an open-label fashion, which will be conducted over a period of 12 weeks, same as to cohort one. Only this second cohort is invited back after 12 weeks to complete the follow-up visit (day 168+14 day). OT, olfactory training.