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Long Haul COVID-19Phase 2NCT06204432

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

A Phase 2 study testing Sodium Citrate, Normal Saline and Olfactory Training Kit - "The Olfactory Kit, by AdvancedRx" in people with Long Haul COVID-19 and Post-Acute COVID-19 Syndrome, run by University of North Carolina, Chapel Hill at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Sodium Citrate, Normal Saline and Olfactory Training Kit - "The Olfactory Kit, by AdvancedRx"
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteUnited States
Study dates
1 Dec 2023to Dec 2025
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

Other trials in United States

About this study

Official title: Efficacy of Adjunctive Sodium Citrate in Smell Retraining for People With Post-Acute Sequelae COVID-19 Olfactory Dysfunction

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:

Read more
  • 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.

Read the detailed description

Background: Loss of sense of smell is a hallmark of COVID-19 infection. While about 80% of post-COVID olfactory dysfunction (OD) will experience some spontaneous recovery within 2 months of initial infection, about 20% will continue to suffer long-term.1 Participants with persistent OD suffer great disability including loss of pleasure with eating leading to weight loss and/or gain and other health risks, including possible dementia. Further, loss of smell may lead to harm, with chief examples of inability to smell gas leaks or food that has gone bad. Currently, use of "smell retraining" is recognized internationally as the most accepted method to treat patients with OD, including post-viral or post-infectious OD.2 Some authors have extrapolated that smell retraining may be of benefit in post-COVID OD, however, data is sparse.3

Increased extracellular calcium has been shown to inhibit the olfaction cascade occurring in the nose by either phosphorylating adenylate cyclase or by interacting and decreasing cyclic nucleotide-gated channels sensitivity to cyclin nucleotides. Several studies have been performed to date using sodium citrate administered as a nasal spray to effectively reduce extracellular calcium resulting in temporary sense of smell benefit in those who have smell loss from a variety of causes, most significantly, post-viral or post-infectious loss (PIOD).

Several studies over the last two decades have examined the effect of sodium citrate on olfactory function in those with OD (mainly post-infectious OD) all of which have shown acute improvement in smell, peaking typically around 1 hour after application.4-7 Most recently, in 2021 Whitcroft et al conducted a controlled clinical trial on 60 PIOD participants. They applied sodium citrate intranasal spray to participants' right nostril for two weeks and olfaction was evaluated by Sniffin' Sticks composite TDI score both before the trial and after 2 weeks of sodium citrate use. They found a significant improvement in TDI score, though not reaching clinical significance. Further, while the proportion of participants reporting parosmia did not change, there was a significant reduction in participants reporting phantosmia.8

The hypothesis is that the administration of sodium citrate to the nasal cavity, providing a temporary improvement in sense of smell, before the performance of smell retraining may augment its effects and yield better recovery in post-COVID-19 OD.

Purpose: 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.

Participants: Adults (> 18 years) with > 3 months of subjective olfactory loss.

Methods: All participants will undergo initial smell testing with the University of Pennsylvania Smell Identification Test (UPSIT) to confirm smell loss before enrollment.

Following screening and consent, enrollment will involve collecting participant data such as medication allergies, time between COVID-19 infection and smell loss, previous smell loss therapies tried, presence of gustatory dysfunction, and use of paxlovid. Participants; olfaction will then be objectively evaluated using "Sniffin' Sticks," a validated psychophysical tool that allows for more detailed assessment of odor threshold, discrimination, and identification.

Participants will be randomized into two groups and blinded. The Sodium Citrate arm will apply a nasal spray of sodium citrate (0.5 mL per nostril) and then perform olfactory training exercises, twice a day for 12 weeks The Normal Saline arm will apply a spray of normal saline (0.5 mL per nostril) and then perform olfactory training exercises, twice a day for 12 weeks. Olfactory training will involve mindful inhalation of 4 primary odortants (lavender, clove, eucalyptus, and lemon), at least 20 seconds for each.

All materials will be provided by AdvancedRx, who will also perform the randomization to ensure investigators are blind as well. Nasal sprays will be shipped in 1-month quantities and adherence will be checked at the end of each month by assessing the amount of spray left in each bottle. During the 12 weeks, at days 7, 28, and 56, investigators will contact the participants to discuss if any adverse events have occurred.

At the end of the 12 weeks, "Sniffin' Sticks" assessment will be repeated, and results compared within and between the groups. Also, the number of eligible participants encountered, the number enrolled, the number who completed the study, the adherence rate, and the adverse event rates will be assessed within the overarching 1 year study period.

Being tested
Sodium Citrate, Normal Saline, Olfactory Training Kit - "The Olfactory Kit, by AdvancedRx"
Keywords
Olfaction disorders, Sodium citrate, COVID-19, Olfactory training
Medical subject headings
Post-Acute COVID-19 Syndrome, Anosmia, Olfaction Disorders, COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sodium CitrateDrug

    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.

  • Normal SalineDrug

    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.

  • 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

Study groups in NCT06204432
Study groupRoleWhat they receive
Normal SalinePlacebo comparatorThe Normal Saline arm will use normal saline nasal spray and olfactory training twice a day for 12 weeks.
Receives: Drug: Normal Saline; Other: Olfactory Training Kit - "The Olfactory Kit, by AdvancedRx"
Sodium CitrateExperimentalThe Sodium Citrate arm will use sodium citrate nasal spray and olfactory training twice a day for 12 weeks.
Receives: Drug: Sodium Citrate; Other: Olfactory Training Kit - "The Olfactory Kit, by AdvancedRx"

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Number of Eligible Patients

    The Number of Eligible Patients Who Meet the Inclusion Criteria

    Measured: 1 year

  2. 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.

    Measured: 1 year

  3. The Proportion of Participants Who Complete the Study

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

    Measured: 1 year

  4. Proportion of Participants Who Report Minor or Severe Adverse Events

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

    Measured: 1 year

  5. Adherence Rate Distribution

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

    Measured: 1, 4, 8, and 12 weeks

Secondary outcomes (1)
  1. Change in Sniffin' Sticks Score

    Olfactory testing with Sniffin' Sticks, specifically assessing aspects of olfactory threshold, discrimination, and identification abilities, will be performed after each participant's completion of the intervention.The Sniffin' Sticks assessment is an evaluation of a person's olfactory performance through three subtests, namely the threshold test, identification test, and discrimination test (TDI). The test uses pen-like bodies that contain a fiber stick filled with scents. To perform the test, the cap is removed, and the patient smells the scent on the tip of the pen. The odor threshold test that uses n-butanol and involves a single staircase, the odor discrimination test that presents 16 pairs of odorants and requires triple forced choice, and the odor identification test that presents 16 common odorants and requires multiple forced choice from four verbal items per test odorant. Each test is scored 0 to 16, with 16 representing good olfaction and 0 representing poor olfaction.

    Measured: Baseline, 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2024
  2. Study start1 Dec 2023
  3. Primary completionDec 2025 (estimated)
  4. Study completionDec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06204432
Sponsor's protocol ID
22-2829
Status last verified
Feb 2025
First submitted
10 Jan 2024
Last updated
20 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 34485883
  • 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.

    PubMed 32660334
  • 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.

    PubMed 35004126
  • 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.

    PubMed 16008069
  • 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.

    PubMed 27316224
  • 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.

    PubMed 27860366
  • 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.

    PubMed 28339165
  • 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.

    PubMed 33471169

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sodium Citrate, Normal Saline and Olfactory Training Kit - "The Olfactory Kit, by AdvancedRx" in people with Long Haul COVID-19 and Post-Acute COVID-19 Syndrome, run by University of North Carolina, Chapel Hill at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 20 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Number of Eligible Patients (time frame: 1 year). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06204432, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2025.

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