A Phase 2 interventional study of Stellate Ganglion Block and Placebo Sham Injection in COVID-19-Induced Parosmia, sponsored by Washington University School of Medicine. Completed at 1 site in United States. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2025-11-10.
Sponsored by Washington University School of Medicine · Phase 2, Interventional, and Treatment
Chronic olfactory dysfunction, both hyposmia and parosmia, from the COVID-19 pandemic is a growing public health crisis with up to 1.2 million people in the United States affected. Olfactory dysfunction impacts one's quality of life significantly by decreasing the enjoyment of foods, creating environmental safety concerns, and affecting one's ability to perform certain jobs. Olfactory loss is also an independent predictor of anxiety, depression, and even mortality. Recent research by our group (unpublished data) and suggests that parosmias, moreso than hyposmias, can result in increased rates of anxiety, depression, and even suicidal ideation. While the pandemic has increased the interest by the scientific community in combating the burgeoning health crisis, few effective treatments currently exist for olfactory dysfunction. Persistent symptoms after an acute COVID-19 infection, or "Long COVID" symptoms, have been hypothesized to be a result of sympathetic positive feedback loops and dysautonomia. Stellate ganglion blocks have been proposed to treat this hyper-sympathetic activation by blocking the sympathetic neuronal firing and resetting the balance of the autonomic nervous system. Studies prior to the COVID-19 pandemic have supported a beneficial effect of stellate ganglion blocks on olfactory dysfunction, and recent news reports and a published case series have described a dramatic benefit in both olfactory function and other long COVID symptoms in patients receiving stellate ganglion blocks. A previous pilot study using stellate ganglion blocks of 20 participants with persistent COVID-19 olfactory dysfunction resulted modest improvements in subjective olfactory function, smell identification, and olfactory-specific quality-of-life, but it lacked a control group. Therefore, we propose a double-blinded, placebo-controlled randomized clinical trial assessing the efficacy of a stellate ganglion block versus saline injection in a total of up to 140 participants with persistent COVID-19-associated olfactory dysfunction.
One of the hallmark symptoms of infection with SARS-CoV-2 is olfactory dysfunction (OD). While the majority of patients recover from COVID dysosmia, up to 15%-25% have long-term hyposmia and it is estimated that up to 1.2 million people in the United States will experience chronic OD from the COVID-19 pandemic. A unique feature of COVID-19-associated OD is the high rate of persistent parosmia. In one study of 222 patients with COVID-19-associated olfactory dysfunction by Lerner et al, 148 (67%) of these patients experienced parosmia at some point, and estimates of persistent parosmia 6 months after COVID-19 infection range from 25% to 57%.Patients with OD have decreased quality-of-life and have described their lives as if "living in a box." These patients have concerns for environmental safety, decreased enjoyment of their food, depression, anxiety, and even a higher risk of mortality. Unpublished work by our group has demonstrated a relationship between parosmia and increased risk of screening positive for anxiety, depression, and suicidality.
The COVID-19 pandemic has highlighted the importance of the sense of olfaction, but no standard of care treatment for post-viral OD exists. The most commonly used treatment for post-viral OD is olfactory training; however, a large proportion of patients do not receive benefit and continue to have persistent symptoms. A multitude of other therapies have been tried in randomized clinical trials with minimal success, including theophylline, vitamin A, sodium citrate, and intranasal insulin. As a result, there is a critical need for the development of a novel intervention to address the large number of patients with OD due to the COVID-19 pandemic.
The stellate ganglion block (SGB) is proposed to inhibit the sympathetic neural connections within the head, neck, and upper extremity, improve regional blood flow, reduce adrenal hormone concentration, and even reestablish circadian rhythms through modulation of melatonin. The SGB has been used successfully in a multitude of disorders, including post-traumatic stress disorder, migraine, and complex regional pain syndrome. A meta-analysis of 12 clinical trials found that SGB was superior to placebo in reducing pain scores among patients with various sympathetic hyperactivity-associated disorders. Many "long COVID" symptoms, those that persist after recovery from acute COVID-19 infection, are hypothesized to be, at least in part, a result of sympathetic hyperactivity resulting in positive feedback loops. Therefore, the stellate ganglion block (SGB) is hypothesized to reset the balance of the autonomic nervous system and provide relief for long COVID symptoms, including OD.
The SGB was first proposed to treat OD by Lee et al in 2003, where 38 post-viral OD participants were treated with SGB and 13 participants remained untreated as controls. Subjective olfactory function improved in 27 (71%) of the treated participants compared to zero (0%) of the controls. Olfactory perception was improved significantly in the SGB group assessed both by the butanol threshold test and odor identification test. Additional studies by Moon et al noted improvement in OD of various etiologies after repeated SGBs. However, each of these studies were limited by their use of unvalidated outcome measures in a heterogeneous OD population in the pre-COVID era, limiting their external validity to the present day.
A multitude of anecdotal news reports and published case series point to a possible beneficial effect of the SGB on both chronic COVID-19-induced OD and various other long COVID symptoms. Numerous pain management clinics across the country are offering the SGB for long COVID with thousands of dollars of out-of-pocket costs to patients without adequate evidence to justify its use. One case series of 195 parosmic patients noted up to a 75% response rate after SGB.
Recently, our study team completed a prospective, pilot single-arm trial of 20 participants with persistent COVID-19-associated OD who underwent bilateral stellate ganglion blocks and were followed for 1 month post-procedure. At 1-month, 10 (50%) participants experienced at least slight subjective improvement in their OD, 11 (55%) attained a clinically meaningful improvement in smell identification using the UPSIT, and 7 (35%) achieved a clinically meaningful improvement in olfactory-specific QOL. Therefore, we propose a double-blinded, placebo-controlled randomized clinical trial assessing the efficacy of a stellate ganglion block versus saline injection in a total of 140 participants with persistent COVID-19-associated parosmia.
7,990 studies on the registry are indexed under COVID-19; 466 are open to participants now.
This study's enrollment of 48 is below the median of 102 across 4,364 interventional studies indexed under COVID-19.
Browse COVID-19 studies →Washington University School of Medicine is the lead sponsor of 1,803 studies on the registry; 271 are open to participants now.
Of its 329 completed or terminated interventional studies of FDA-regulated products, 216 (66%) 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:
History of conditions known to impact olfactory dysfunction
History of coexisting conditions that make SGB :
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.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
FEV1
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The ultrasound guided stellate ganglion blocks will be performed at the initial visit by a board-certified anesthesiologist and pain management specialist with extensive experience performing these blocks. Laterality of the stellate ganglion blocks will be randomized between the left and right sides of the neck.
Drug: Stellate Ganglion Block
The ultrasound guided placebo sham injections will be performed at the initial visit by a board-certified anesthesiologist and pain management specialist with extensive experience performing these injections. Laterality of the placebo sham injections will be randomized between the left and right sides of the neck.
Drug: Placebo Sham Injection
The stellate ganglion will be identified using ultrasound guidance, and after negative aspiration, 6-8 mL of 1% mepivacaine will be injected near the stellate ganglion.
Also known as: mepivacaine
The stellate ganglion will be identified using ultrasound guidance, and after negative aspiration, 6-8 mL of 0.9% saline will be injected near the stellate ganglion.
Also known as: 0.9% saline
Parosmia Olfactory Dysfunction Outcomes Rating
The primary outcome of the study is to determine the efficacy of a stellate ganglion block (SGB) in improving parosmia-related quality of life compared to a saline injection placebo. The instrument contains 28 total items with each scored on a 5-point Likert scale from 0 (no difficulty) to 4 (complete difficulty or very frequent bother). Higher total scores indicate a greater degree of dysfunction and limitation. The minimal clinically important difference (MCID) for DisODOR being 15 points.
Time frame: 1-mo outcome and 3-mo outcome
Clinical Global Impression - Severity Scale (CGI-S) Smell Loss
The Clinical Global Impression - Improvement Scale (CGI-I) for smell loss (parosmia) is used to measure the overall response to treatment by assessing changes in the clinical condition compared to before the stellate ganglion block. It uses a 7-point Likert scale with the following response options: (1) Much better now than before, (2) Moderately better now than before, (3) Slightly better now than before, (4) About the same, (5) Slightly worse now than before, (6) Moderately worse now than before, and (7) Much worse now than before. Participants who report "slightly better now than before" or greater improvement are classified as responders.
Time frame: 1-mo and 3-mo
Long-COVID Questionnaire
At each follow-up visit, participants are asked to rank their overall improvement in each of the 11 symptoms compared to their symptoms prior to their first SGB. The improvement options are based on the CGI-I 7-point Likert scale. Total scores range from 0-77, with higher scores being worse and lower scores being better.
Time frame: 1 month, 3 months
Olfaction Catastrophizing Scale (OCS)
Participants will be asked to complete the OCS, which measures the negative mental response to smell dysfunction loss. Multiple thoughts/feelings will be assessed on a 5-point Likert scale with a maximum score of 52. Participants will complete the OCS at each study visit to assess the degree of olfactory-related catastrophizing over time.
Time frame: 1 month, 3 months
Hospital Anxiety and Depression Scale (HADS)
Participants will be asked to complete the HADS, which screens for both anxiety and depression in the general population. It consists of 7 questions for anxiety and 7 questions for depression each ranked on a 4-point Likert Scale. A score of 0-7 is considered normal, 8-10 is borderline abnormal anxiety or depression, and a score of 11-21 corresponds with screening positive for anxiety or depression.
Time frame: 1 month, 3 months
Patient Satisfaction With Treatment
Participants will be asked at 1 month "Overall, how satisfied were you with the stellate ganglion block treatment for your parosmia?" with possible answer choices: 1) Completely dissatisfied, 2) Mostly dissatisfied, 3) Somewhat dissatisfied, 4) Neither satisfied or dissatisfied, 5) Somewhat satisfied, 6) Mostly satisfied, 7) Completely satisfied.
Time frame: 1 mo, 3-mo
Assessment of the Blind
Immediately after the injection, participants will be asked "Which intervention do you think you received?" with answer choices of 1) Mepivacaine (active medication) or 2) Saline (placebo). It is performed immediately after the initial injection during the first visit, just prior to discharge.
Time frame: during first visit
Adverse Events Assessment
Any potential adverse events of the stellate ganglion block will be collected from participants.
Time frame: Baseline, 1 month, 3 months
48 participants were enrolled and randomized, with 32 receiving SGB and 16 receiving placebo.
| Milestone | Experimental: Stellate Ganglion Block | Placebo: Sham Injection |
|---|---|---|
| Started | 32 | 16 |
| 1-mo outcome | 31 | 16 |
| 3-mo outcome | 30 | 16 |
| Completed | 30 | 16 |
| Not completed | 2 | 0 |
The primary outcome of the study is to determine the efficacy of a stellate ganglion block (SGB) in improving parosmia-related quality of life compared to a saline injection placebo. The instrument contains 28 total items with each scored on a 5-point Likert scale from 0 (no difficulty) to 4 (complete difficulty or very frequent bother). Higher total scores indicate a greater degree of dysfunction and limitation. The minimal clinically important difference (MCID) for DisODOR being 15 points.
| score on a scale 0-112 | Experimental: Stellate Ganglion Block | Placebo: Sham Injection |
|---|---|---|
| 1-mo | 9 (-19 to 54) | 9 (-13 to 82) |
| 3-mo | 14 (-21 to 59) | 11 (-16 to 60) |
The Clinical Global Impression - Improvement Scale (CGI-I) for smell loss (parosmia) is used to measure the overall response to treatment by assessing changes in the clinical condition compared to before the stellate ganglion block. It uses a 7-point Likert scale with the following response options: (1) Much better now than before, (2) Moderately better now than before, (3) Slightly better now than before, (4) About the same, (5) Slightly worse now than before, (6) Moderately worse now than before, and (7) Much worse now than before. Participants who report "slightly better now than before" or greater improvement are classified as responders.
| Participants | Experimental: Stellate Ganglion Block | Placebo: Sham Injection |
|---|---|---|
| 1-mo — slightly to much better | 8 | 4 |
| 1-mo — about the same | 22 | 11 |
| 1-mo — slightly to much worse | 1 | 1 |
| 3-mo — slightly to much better | 13 | 6 |
| 3-mo — about the same | 13 | 10 |
| 3-mo — slightly to much worse | 4 | 0 |
At each follow-up visit, participants are asked to rank their overall improvement in each of the 11 symptoms compared to their symptoms prior to their first SGB. The improvement options are based on the CGI-I 7-point Likert scale. Total scores range from 0-77, with higher scores being worse and lower scores being better.
| score on a scale 0-77 | Experimental: Stellate Ganglion Block | Placebo: Sham Injection |
|---|---|---|
| 1-mo | 44 (21 to 68) | 45 (11 to 69) |
| 3-mo | 44 (16 to 74) | 44 (11 to 53) |
Participants will be asked to complete the OCS, which measures the negative mental response to smell dysfunction loss. Multiple thoughts/feelings will be assessed on a 5-point Likert scale with a maximum score of 52. Participants will complete the OCS at each study visit to assess the degree of olfactory-related catastrophizing over time.
| units on a scale | Experimental: Stellate Ganglion Block | Placebo: Sham Injection |
|---|---|---|
| 1-mo | 8 (-6 to 32) | 6 (-5 to 38) |
| 3-mo | 7 (-13 to 31) | 5 (-8 to 33) |
Participants will be asked to complete the HADS, which screens for both anxiety and depression in the general population. It consists of 7 questions for anxiety and 7 questions for depression each ranked on a 4-point Likert Scale. A score of 0-7 is considered normal, 8-10 is borderline abnormal anxiety or depression, and a score of 11-21 corresponds with screening positive for anxiety or depression.
| units on a scale | Experimental: Stellate Ganglion Block | Placebo: Sham Injection |
|---|---|---|
| 1-mo HADS anxiety | 1 (-6 to 10) | 1 (-5 to 10) |
| 3-mo HADS anxiety | 1 (-8 to 18) | 1 (-8 to 8) |
| 1-mo HADS depression | 1 (-7 to 10) | 1 (-4 to 8) |
| 3-mo HADS depression | 8 (-6 to 32) | 3 (-7 to 7) |
Participants will be asked at 1 month "Overall, how satisfied were you with the stellate ganglion block treatment for your parosmia?" with possible answer choices: 1) Completely dissatisfied, 2) Mostly dissatisfied, 3) Somewhat dissatisfied, 4) Neither satisfied or dissatisfied, 5) Somewhat satisfied, 6) Mostly satisfied, 7) Completely satisfied.
| Participants | Experimental: Stellate Ganglion Block | Placebo: Sham Injection |
|---|---|---|
| 1-mo — Somewhat to completely satisfied | 8 | 5 |
| 1-mo — Neither satisfied or dissatisfied | 10 | 4 |
| 1-mo — Somewhat to completely dissatisfied | 13 | 7 |
| 3-mo — Somewhat to completely satisfied | 11 | 5 |
| 3-mo — Neither satisfied or dissatisfied | 1 | 5 |
| 3-mo — Somewhat to completely dissatisfied | 18 | 6 |
Immediately after the injection, participants will be asked "Which intervention do you think you received?" with answer choices of 1) Mepivacaine (active medication) or 2) Saline (placebo). It is performed immediately after the initial injection during the first visit, just prior to discharge.
| Participants | Experimental: Stellate Ganglion Block | Placebo: Sham Injection |
|---|---|---|
| 1-mo blind assessment | 18 | 14 |
| 3-mo blind assessment | 12 | 4 |
Any potential adverse events of the stellate ganglion block will be collected from participants.
Results for this outcome have not been posted.
Collected over Adverse events will be recorded from the time of dose administration (the stellate ganglion block or placebo injection) through the post-dose period and up to the final follow-up visit at approximately 3 months after the injection. The study team will monitor and document all adverse events throughout this entire timeframe.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Experimental: Stellate Ganglion Block | 0/31 (0%) | 0/31 (0%) | 25/31 (80.6%) |
| Placebo: Sham Injection | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) |
| Event | Experimental: Stellate Ganglion Block | Placebo: Sham Injection |
|---|---|---|
| transient voice hoarsenessGeneral disorders | 9/31 | 0/16 |
| nasal congestionGeneral disorders | 6/31 | 0/16 |
| headache or migraineGeneral disorders | 5/31 | 1/16 |
| lightheadedness or dizzinessGeneral disorders | 5/31 | 1/16 |
Of 48 randomized participants,32 were randomized to SGB and 16 to placebo arm.
| Age, Continuous(years) | Stellate Ganglion Block | Placebo Sham Injections | Total |
|---|---|---|---|
| Median | 45 (19 to 64) | 55 (26 to 64) | 46 (19 to 64) |
| Sex: Female, Male(Participants) | Stellate Ganglion Block | Placebo Sham Injections | Total |
|---|---|---|---|
| Female | 26 | 13 | 39 |
| Male | 6 | 3 | 9 |
| Ethnicity (NIH/OMB)(Participants) | Stellate Ganglion Block | Placebo Sham Injections | Total |
|---|---|---|---|
| Hispanic or Latino | 3 | 1 | 4 |
| Not Hispanic or Latino | 29 | 15 | 44 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Stellate Ganglion Block | Placebo Sham Injections | Total |
|---|---|---|---|
| Race — Black | 1 | 2 | 3 |
| Race — White | 31 | 14 | 45 |
| Region of Enrollment(participants) | Stellate Ganglion Block | Placebo Sham Injections | Total |
|---|---|---|---|
| United States | 32 | 16 | 48 |
| The Parosmia Olfactory Dysfunction Outcomes Rating (DisODOR)(scores ranging 0-116) | Stellate Ganglion Block | Placebo Sham Injections | Total |
|---|---|---|---|
| Median | 63 (33 to 97) | 66 (26 to 95) | 66 (26 to 97) |
| The Clinical Global Impression - Severity Scale (CGI-S) smell loss(Participants) | Stellate Ganglion Block | Placebo Sham Injections | Total |
|---|---|---|---|
| No loss | 1 | 1 | 2 |
| Very mild to mild loss | 6 | 5 | 11 |
| Moderate to severe loss | 25 | 10 | 35 |
| The Clinical Global Impression - Severity Scale (CGI-S) smell distortion(Participants) | Stellate Ganglion Block | Placebo Sham Injections | Total |
|---|---|---|---|
| No distortion | 3 | 2 | 5 |
| very mild to mild distortion | 1 | 1 | 2 |
| Moderate to severe distortion | 28 | 13 | 41 |
6 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Oct 2023 to primary completion in Sep 2024, 10 months.
Results were first posted in Nov 2025, 1 year 1 month after primary completion.
Of 359 non-industry phase 2 interventional studies under COVID-19, half reached primary completion within 11 months of starting (the median), counting those still running; a quarter within 5 and three quarters within 18. This study's 10 months is close to that.
Counting every sponsor, half of 582 studies reached it within 9 months; a quarter within 5 and three quarters within 16.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Oct 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Mepivacaine
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