Sodium Citrate in Smell Retraining for People With Post-COVID-19 Olfactory Dysfunction

NCT06204432 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 22-2829
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this pilot study is to assess the feasibility and impact of using sodium citrate nasal spray as an adjunct to olfactory retraining in participants with long-term post-COVID-19 olfactory dysfunction. The main questions it aims to answer are:

• Is sodium citrate nasal spray in addition to smell retraining feasible for participants to use in terms of participant need/desire, adherence, and adverse events?
• Does sodium citrate nasal spray in addition to smell retraining further improve smell as compared to normal saline spray and smell retraining? Participants will:
• Provide consent for enrollment.
• Undergo smell testing via Sniffin' Sticks.
• Use a nasal spray (either sodium citrate or normal saline) followed by olfactory retraining twice a day for 12 weeks.
• Return for follow-up Sniffin' Sticks testing. Researchers will compare the sodium citrate group and the normal saline group to determine differences in smell improvement.

Conditions

Long Haul COVID-19; Post-Acute COVID-19 Syndrome; Anosmia; Olfaction Disorders

Keywords

Olfaction disorders; Sodium citrate; COVID-19; Olfactory training

Outcome Measures

Primary Outcomes (5)

• The Number of Eligible Patients

  The Number of Eligible Patients Who Meet the Inclusion Criteria

  1 year

• The Proportion of Participants Who Were Enrolled in the Study

  The Proportion of Participants Who Were Enrolled in the Study and Completed the First Sniffin' Sticks Test.

  1 year

• The Proportion of Participants Who Complete the Study

  The Proportion of Participants Who Complete the 12 Weeks of Smell Retraining With Nasal Spray.

  1 year

• Proportion of Participants Who Report Minor or Severe Adverse Events

  The proportion of patients who report minor or severe adverse events during the study.

  1 year

• Adherence Rate Distribution

  The distribution of adherence rates (2x / day as instructed, 1x / day, \<1x / day).

  1, 4, 8, and 12 weeks

Secondary Outcomes (1)

• Change in Sniffin' Sticks Score

  Baseline, 12 weeks

Study Arms (2)

Normal Saline

PLACEBO COMPARATOR

The Normal Saline arm will use normal saline nasal spray and olfactory training twice a day for 12 weeks.

Drug: Normal Saline; Other: Olfactory Training Kit - "The Olfactory Kit, by AdvancedRx"

Sodium Citrate

EXPERIMENTAL

The Sodium Citrate arm will use sodium citrate nasal spray and olfactory training twice a day for 12 weeks.

Drug: Sodium Citrate; Other: Olfactory Training Kit - "The Olfactory Kit, by AdvancedRx"

Interventions

Sodium Citrate DRUG

Those randomized to the Sodium Citrate arm will use 1 mL of 2.5% sodium citrate (3.5g/140 mL, pH 7.4, 298 mOsmol/L), 0.5 mL in each nostril, twice a day via an atomizer followed by olfactory training.

Sodium Citrate

Normal Saline DRUG

Those randomized to the Normal Saline arm will use 1 mL of normal saline, 0.5 mL in each nostril, twice a day via an atomizer followed by olfactory training.

Normal Saline

Olfactory Training Kit - "The Olfactory Kit, by AdvancedRx" OTHER

All participants, regardless of study arm they are randomized to, will participate in olfactory training twice a day after use of their nasal spray

Normal Saline; Sodium Citrate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male and female, ages greater than or equal to 18 years.
• Patients with persistent olfactory dysfunction originating at the time of a confirmed COVID-19 positive test occurring greater than 3 months ago.
• Ability to use nasal spray and be willing to adhere to the nasal spray and olfactory training regimen

You may not qualify if:

• Treatment with another investigational drug or other intervention for olfactory dysfunction within the prior three months.
• Current smoker or inhaled tobacco use within the last three months.
• History of chronic sinusitis or nasal polyps.
• History of olfactory dysfunction following head trauma.
• History of sinus or skull base surgery.
• History of persistent olfactory dysfunction related to any other prior cause other than COVID-19 infection.
• Congenital anosmia.
• Inability to return to UNC Health for follow-up.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (8)

• Bacon DR, Onuorah P, Murr A, Wiesen CA, Oakes J, Thorp BD, Zanation AM, Ebert CS Jr, Wohl D, Senior BA, Kimple AJ. COVID-19 related olfactory dysfunction prevalence and natural history in ambulatory patients. Rhinol Online. 2021;4(4):131-139. doi: 10.4193/rhinol/21.034. Epub 2021 Aug 13.

  PMID: 34485883 BACKGROUND

• Kattar N, Do TM, Unis GD, Migneron MR, Thomas AJ, McCoul ED. Olfactory Training for Postviral Olfactory Dysfunction: Systematic Review and Meta-analysis. Otolaryngol Head Neck Surg. 2021 Feb;164(2):244-254. doi: 10.1177/0194599820943550. Epub 2020 Jul 14.

  PMID: 32660334 BACKGROUND

• Wu TJ, Yu AC, Lee JT. Management of post-COVID-19 olfactory dysfunction. Curr Treat Options Allergy. 2022;9(1):1-18. doi: 10.1007/s40521-021-00297-9. Epub 2022 Jan 4.

  PMID: 35004126 BACKGROUND

• Panagiotopoulos G, Naxakis S, Papavasiliou A, Filipakis K, Papatheodorou G, Goumas P. Decreasing nasal mucus Ca++ improves hyposmia. Rhinology. 2005 Jun;43(2):130-4.

  PMID: 16008069 BACKGROUND

• Whitcroft KL, Merkonidis C, Cuevas M, Haehner A, Philpott C, Hummel T. Intranasal sodium citrate solution improves olfaction in post-viral hyposmia. Rhinology. 2016 Dec 1;54(4):368-374. doi: 10.4193/Rhino16.054.

  PMID: 27316224 BACKGROUND

• Whitcroft KL, Ezzat M, Cuevas M, Andrews P, Hummel T. The effect of intranasal sodium citrate on olfaction in post-infectious loss: results from a prospective, placebo-controlled trial in 49 patients. Clin Otolaryngol. 2017 Jun;42(3):557-563. doi: 10.1111/coa.12789. Epub 2016 Dec 7.

  PMID: 27860366 BACKGROUND

• Philpott CM, Erskine SE, Clark A, Leeper A, Salam M, Sharma R, Murty GE, Hummel T. A randomised controlled trial of sodium citrate spray for non-conductive olfactory disorders. Clin Otolaryngol. 2017 Dec;42(6):1295-1302. doi: 10.1111/coa.12878. Epub 2017 Apr 17.

  PMID: 28339165 BACKGROUND

• Whitcroft KL, Gunder N, Cuevas M, Andrews P, Menzel S, Haehner A, Hummel T. Intranasal sodium citrate in quantitative and qualitative olfactory dysfunction: results from a prospective, controlled trial of prolonged use in 60 patients. Eur Arch Otorhinolaryngol. 2021 Aug;278(8):2891-2897. doi: 10.1007/s00405-020-06567-7. Epub 2021 Jan 20.

  PMID: 33471169 BACKGROUND

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Anosmia; Olfaction Disorders; COVID-19

Interventions

Sodium Citrate; Saline Solution

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Citric Acid; Citrates; Tricarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Brent A. Senior, MD, FACS, FARS

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participants, care providers, investigators, and outcome assessors will all be blinded to which study arm a participant is in. Only the compounding pharmacy will have access to the non-blinded group assignments, and they oversee the randomization.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to one of two intervention groups. One will use sodium citrate nasal spray and olfactory training twice a day for 12 weeks. The other will use normal saline nasal spray and olfactory training twice a day for 12 weeks.

Study Record Dates

• First Submitted: January 10, 2024
• First Posted: January 12, 2024
• Study Start: December 1, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: February 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)