COVID-19 Anosmia Study

Covid19 Clinical Trial

Official title:

COVID-19 Anosmia Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04495816
• Other study ID #: GCO 20-1132
• Status: Completed
• Phase: Phase 2
• Start date: July 15, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: October 2023
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 139
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anosmia
• COVID-19
• Covid19

Intervention

Drug:
• Omega-3 Fatty Acid Supplement
Participants randomized to this arm will be instructed to take two of the softgels they received per day for 6 weeks. They will receive softgels containing 1,000 mg of omega-3 fatty acid. 1000 mg of omega-3 fatty acid blend including 683 mg Eicosapentaenoic Acid and 252 mg Docosahexaenoic Acid
• Placebo/Control
Patients randomized to this arm will also be instructed to take two of the softgels they received per day for 6 weeks. They will receive placebo softgels that are indistinguishable from those containing fish oil.

Locations

Country	Name	City	State
United States	Mount Sinai Hospital	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai

Country where clinical trial is conducted

United States, 

References & Publications (15)

Boesveldt S, Postma EM, Boak D, Welge-Luessen A, Schopf V, Mainland JD, Martens J, Ngai J, Duffy VB. Anosmia-A Clinical Review. Chem Senses. 2017 Sep 1;42(7):513-523. doi: 10.1093/chemse/bjx025. Erratum In: Chem Senses. 2017 Sep 1;42(7):607. — View Citation

Cavazzana A, Larsson M, Munch M, Hahner A, Hummel T. Postinfectious olfactory loss: A retrospective study on 791 patients. Laryngoscope. 2018 Jan;128(1):10-15. doi: 10.1002/lary.26606. Epub 2017 May 29. — View Citation

Croy I, Nordin S, Hummel T. Olfactory disorders and quality of life--an updated review. Chem Senses. 2014 Mar;39(3):185-94. doi: 10.1093/chemse/bjt072. Epub 2014 Jan 15. — View Citation

Damm M, Pikart LK, Reimann H, Burkert S, Goktas O, Haxel B, Frey S, Charalampakis I, Beule A, Renner B, Hummel T, Huttenbrink KB. Olfactory training is helpful in postinfectious olfactory loss: a randomized, controlled, multicenter study. Laryngoscope. 2014 Apr;124(4):826-31. doi: 10.1002/lary.24340. Epub 2013 Sep 19. — View Citation

Ekstrom I, Sjolund S, Nordin S, Nordin Adolfsson A, Adolfsson R, Nilsson LG, Larsson M, Olofsson JK. Smell Loss Predicts Mortality Risk Regardless of Dementia Conversion. J Am Geriatr Soc. 2017 Jun;65(6):1238-1243. doi: 10.1111/jgs.14770. Epub 2017 Mar 22. — View Citation

Eliezer M, Hautefort C, Hamel AL, Verillaud B, Herman P, Houdart E, Eloit C. Sudden and Complete Olfactory Loss of Function as a Possible Symptom of COVID-19. JAMA Otolaryngol Head Neck Surg. 2020 Jul 1;146(7):674-675. doi: 10.1001/jamaoto.2020.0832. No abstract available. — View Citation

Fonteyn S, Huart C, Deggouj N, Collet S, Eloy P, Rombaux P. Non-sinonasal-related olfactory dysfunction: A cohort of 496 patients. Eur Ann Otorhinolaryngol Head Neck Dis. 2014 Apr;131(2):87-91. doi: 10.1016/j.anorl.2013.03.006. Epub 2014 Mar 26. — View Citation

Hendriks AP. Olfactory dysfunction. Rhinology. 1988 Dec;26(4):229-51. — View Citation

Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, Dequanter D, Blecic S, El Afia F, Distinguin L, Chekkoury-Idrissi Y, Hans S, Delgado IL, Calvo-Henriquez C, Lavigne P, Falanga C, Barillari MR, Cammaroto G, Khalife M, Leich P, Souchay C, Rossi C, Journe F, Hsieh J, Edjlali M, Carlier R, Ris L, Lovato A, De Filippis C, Coppee F, Fakhry N, Ayad T, Saussez S. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020 Aug;277(8):2251-2261. doi: 10.1007/s00405-020-05965-1. Epub 2020 Apr 6. — View Citation

Pekala K, Chandra RK, Turner JH. Efficacy of olfactory training in patients with olfactory loss: a systematic review and meta-analysis. Int Forum Allergy Rhinol. 2016 Mar;6(3):299-307. doi: 10.1002/alr.21669. Epub 2015 Dec 1. — View Citation

Reden J, Herting B, Lill K, Kern R, Hummel T. Treatment of postinfectious olfactory disorders with minocycline: a double-blind, placebo-controlled study. Laryngoscope. 2011 Mar;121(3):679-82. doi: 10.1002/lary.21401. Epub 2011 Feb 1. — View Citation

Reden J, Mueller A, Mueller C, Konstantinidis I, Frasnelli J, Landis BN, Hummel T. Recovery of olfactory function following closed head injury or infections of the upper respiratory tract. Arch Otolaryngol Head Neck Surg. 2006 Mar;132(3):265-9. doi: 10.1001/archotol.132.3.265. — View Citation

Sorokowska A, Drechsler E, Karwowski M, Hummel T. Effects of olfactory training: a meta-analysis. Rhinology. 2017 Mar 1;55(1):17-26. doi: 10.4193/Rhino16.195. — View Citation

Vaira LA, Salzano G, Deiana G, De Riu G. Anosmia and Ageusia: Common Findings in COVID-19 Patients. Laryngoscope. 2020 Jul;130(7):1787. doi: 10.1002/lary.28692. Epub 2020 Apr 15. — View Citation

Vukkadala N, Qian ZJ, Holsinger FC, Patel ZM, Rosenthal E. COVID-19 and the Otolaryngologist: Preliminary Evidence-Based Review. Laryngoscope. 2020 Nov;130(11):2537-2543. doi: 10.1002/lary.28672. Epub 2020 Apr 24. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Brief Smell Identification Test (BSIT)	Change in BSIT. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.	Week 0 and Week 6
Primary	Change in Brief Smell Identification Test (BSIT) in Participants With Severe Olfactory Dysfunction	Mean change in BSIT in participants with severe olfactory dysfunction defined as BSIT = 7. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.	Week 0 and Week 6
Primary	Change in Brief Smell Identification Test (BSIT) in Participants With Laboratory-Confirmed COVID-19 and Severe Olfactory Dysfunction	Mean change in BSIT in participants with laboratory-confirmed COVID-19. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.	Week 0 and Week 6
Primary	Change in Brief Smell Identification Test (BSIT) in Participants With Laboratory-Confirmed COVID-19	Mean change in BSIT in participants with severe olfactory dysfunction defined as BSIT = 6. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.	Week 0 and Week 6
Secondary	Modified Brief Questionnaire of Olfactory Dysfunction (mQOD-NS)	The modified Brief Questionnaire of Olfactory Dysfunction - Negative Statements (QOD-NS) survey is a 17-item instrument, each item graded on a scale from 0 to 3, with total scale range from 0 to 51. Higher score indicates better olfactory-specific quality of life (QOL).	baseline, weeks 1, 2, 4 and 6 after softgel initiation
Secondary	Sinonasal Outcomes Test (SNOT-22)	Sino-Nasal Outcome Test (SNOT-22) is a 22-item instrument, total scale range from 0 to 110, higher score indicates more severe QOL impact.	baseline, weeks 1, 2, 4 and 6 after softgel initiation