A Phase 2 interventional study of Sodium Citrate and Normal Saline in Long Haul COVID-19, Post-Acute COVID-19 Syndrome and Anosmia, sponsored by University of North Carolina, Chapel Hill. Active, not recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-02-20.
Sponsored by University of North Carolina, Chapel Hill · Phase 2, Interventional, and Treatment
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:
Participants will:
Researchers will compare the sodium citrate group and the normal saline group to determine differences in smell improvement.
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.
604 studies on the registry are indexed under Post-Acute COVID-19 Syndrome; 201 are open to participants now.
This study's planned enrollment of 60 is close to the median of 60 across 416 interventional studies indexed under Post-Acute COVID-19 Syndrome.
Browse Post-Acute COVID-19 Syndrome studies →University of North Carolina, Chapel Hill is the lead sponsor of 1,372 studies on the registry; 133 are open to participants now.
Of its 161 completed or terminated interventional studies of FDA-regulated products, 139 (86%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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"
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"
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.
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.
All participants, regardless of study arm they are randomized to, will participate in olfactory training twice a day after use of their nasal spray
The Number of Eligible Patients
The Number of Eligible Patients Who Meet the Inclusion Criteria
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 1 year
Adherence Rate Distribution
The distribution of adherence rates (2x / day as instructed, 1x / day, \<1x / day).
Time frame: 1, 4, 8, and 12 weeks
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.
Time frame: Baseline, 12 weeks
Plan to share: No
This study is active, not recruiting, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Sodium Citrate
Post-Acute COVID-19 Syndrome →
University of North Carolina, Chapel Hill →