Clinical trial NCT04495816: COVID-19 Anosmia Study
Official title: COVID-19 Anosmia Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anosmia
Covid19
Keywords: Novel Coronavirus
Anosmia
Smell Loss
Parosmia
Fish Oil Supplement
Omega-3 Fatty Acid Supplements
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2020-08-03
Enrollment: 139
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized into treatment and control groups. The treatment group will receive omega-3-fatty acid supplementation (1000 mg of omega-3 fatty acid blend including 683 mg Eicosapentaenoic Acid and 252 mg Docosahexaenoic Acid) to be taken twice daily for 6 weeks. The control arm will receive a placebo pill to be taken twice daily.
Primary purpose: TREATMENT

Brief summary: To capture the natural history of COVID-19 associated olfactory dysfunction as measured by two patient reported outcome measures (SNOT-22, QOD-NS) and a 6-week BSIT with a comparison to an intervention arm receiving daily omega-3 supplements.

Detailed description: Infection with the novel coronavirus (COVID-19) has been linked to new-onset olfactory dysfunction, often as the only presenting symptom. In one multicenter European study, 85.6% of patients with mild to moderate symptoms reported hyposmia or anosmia with early recovery of olfactory function in just under half of patients. However, the pathogenesis and natural history of COVID-19 related olfactory dysfunction is poorly understood.

Anosmia most commonly arises in association with sinonasal disease or post-infectious or post-traumatic disorders. Notably, olfactory loss has been associated with impaired quality of life, higher rates of depression, and even increased mortality risk. Spontaneous recovery has been observed in patients with post- infectious olfactory dysfunction, typically over a period of months to years, with an estimated one-third of patients demonstrating meaningful improvement after one year.

Smell retraining therapy appears to be an effective therapeutic option for patients with post-infectious olfactory dysfunction, particularly for patients who initiate treatment within one year from onset of symptoms, but requires an intervention period of at least three to four months. Various pharmacotherapies have been investigated in the treatment of post-infectious anosmia but none have clearly demonstrated utility with the exception of a possible benefit for nasal steroid irrigations in combination with smell retraining therapy.

More recently, omega-3 polyunsaturated fat supplementation has emerged as a promising pharmacotherapy for olfactory dysfunction in patients without sinonasal disease. Omega-3 fatty acid deficient mice demonstrate evidence of olfactory dysfunction and mice receiving omega-3 fatty acids have improved recovery after peripheral nerve injury, which has been linked to neuroprotective effects mediated through anti-oxidant and anti-inflammatory pathways. In humans, a large cross-sectional study found that older adults with higher dietary fat intake had lower incidence of olfactory impairment. From a clinical perspective, patients without sinonasal disease receiving postoperative omega-3 fatty acid supplementation after endoscopic endonasal skull base surgery in a randomized control trial demonstrated a significantly greater rate of return of normal olfactory dysfunction.

Little is known about either the natural history of olfactory dysfunction associated with COVID-19 infection or about the therapeutic efficacy of omega-3 fatty acid supplementation in patients with post-viral anosmia. The study team hopes to gain a better understanding of each through a randomized double-blind placebo control study that assesses both objective and subjective perception of olfactory dysfunction over a period of 6 weeks after infection.

Eligibility criteria: Inclusion Criteria:

* Adults (18 years of age or older) with self-reported new-onset olfactory dysfunction
* Positive COVID-19 diagnosis will be deemed eligible for inclusion.

Exclusion Criteria:

* Patients \<18 years of age
* Patients who are unable to provide informed consent
* Patients without a positive COVID-19 PCR result obtained through nasopharyngeal swab - Patients with a COVID-19 diagnosis but without self-reported anosmia
* Patients with severe COVID-19 disease as defined by the Mouth Sinai Health System Treatment Guidelines for SARS-COV-2 (requiring high flow nasal cannula, non-rebreather, CPAP/BIPAP, or mechanical ventilation OR patients requiring pressor medication OR patients with evidence of end organ damage)
* Patients with pre-existing self-reported olfactory dysfunction
* Patients with a history of chronic nasal/sinus infections (rhinosinusitis) or history of endoscopic sinus surgery
* Patients using nasal steroid sprays or irrigations for any reason
* Patients who are prisoners of the state
* Patients who have psychiatric or developmental disorder conditions that may impair ability to provide informed consent
* Patients will also be excluded if they have an allergy to fish or an omega-3 supplement, or do not eat fish or fish- containing substances for any reason

Primary outcomes:
measure: Change in Brief Smell Identification Test (BSIT)
timeFrame: Week 0 and Week 6
measure: Change in Brief Smell Identification Test (BSIT) in Participants With Severe Olfactory Dysfunction
timeFrame: Week 0 and Week 6
measure: Change in Brief Smell Identification Test (BSIT) in Participants With Laboratory-Confirmed COVID-19 and Severe Olfactory Dysfunction
timeFrame: Week 0 and Week 6
measure: Change in Brief Smell Identification Test (BSIT) in Participants With Laboratory-Confirmed COVID-19
timeFrame: Week 0 and Week 6
Secondary outcomes:
measure: Modified Brief Questionnaire of Olfactory Dysfunction (mQOD-NS)
timeFrame: baseline, weeks 1, 2, 4 and 6 after softgel initiation
measure: Sinonasal Outcomes Test (SNOT-22)
timeFrame: baseline, weeks 1, 2, 4 and 6 after softgel initiation
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Alfred-Marc Iloreta, MD
role: PRINCIPAL_INVESTIGATOR
References:
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