Stellate Ganglion Block for COVID-induced Parosmia (SGB)

October 25, 2025 updated by: Washington University School of Medicine

Stellate Ganglion Block for the Treatment of COVID-19-Induced Parosmia: Double-Blinded, Placebo-Controlled Randomized Clinical Trial

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 Recent research by our group (unpublished data) and suggests that parosmias, moreso than hyposmias, can result in increased rates of anxiety, depression, and even suicidal ideation.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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • St Louis, Missouri, United States, 63122
        • Nyssa Fox Farrell

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adults age 18 to 70
  2. Diagnosis of COVID at least 6 months prior to study enrollment with self-reported parosmia
  3. Ability to read, write, and understand English
  4. Score of at least 40 on DiSODOR during screening and at least 25 during Visit 1

Exclusion Criteria:

  1. History of smell loss or change prior to COVID-19 infection

  2. History of conditions known to impact olfactory dysfunction

    1. Chronic rhinosinusitis
    2. History of prior sinonasal or skull base surgery
    3. Neurodegenerative disorders (Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, Lewy body dementia, frontotemporal dementia)
  3. Currently using concomitant therapies specifically for the treatment of olfactory dysfunction
  4. Inability to tolerate a needle injection into the neck

  5. History of coexisting conditions that make SGB contraindicated:

    1. Unilateral vocal cord paralysis
    2. Severe COPD (FEV1 between 30-50% of predicted)
    3. Recent myocardial infarction within the last year
    4. Glaucoma
    5. Cardiac conduction block of any degree
  6. Currently taking blood thinners or antiplatelet agents, including aspirin >81mg.
  7. Allergy to local anesthetic
  8. Inability to extend the neck for any reason (e.g., severe arthritis)
  9. History of prior stellate ganglion block

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Experimental: Stellate Ganglion Block
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 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.
Other Names:
  • mepivacaine
Placebo Comparator: Placebo: Sham Injection
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 0.9% saline will be injected near the stellate ganglion.
Other Names:
  • 0.9% saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Parosmia Olfactory Dysfunction Outcomes Rating
Time Frame: 1-mo outcome and 3-mo outcome

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.
1-mo outcome and 3-mo outcome

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Global Impression - Severity Scale (CGI-S) Smell Loss
Time Frame: 1-mo and 3-mo
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.
1-mo and 3-mo
Long-COVID Questionnaire
Time Frame: 1 month, 3 months

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.
1 month, 3 months
Olfaction Catastrophizing Scale (OCS)
Time Frame: 1 month, 3 months

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.
1 month, 3 months
Hospital Anxiety and Depression Scale (HADS)
Time Frame: 1 month, 3 months
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.
1 month, 3 months
Patient Satisfaction With Treatment
Time Frame: 1 mo, 3-mo
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.
1 mo, 3-mo
Assessment of the Blind
Time Frame: during first visit

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.
during first visit

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events Assessment
Time Frame: Baseline, 1 month, 3 months
Any potential adverse events of the stellate ganglion block will be collected from participants.
Baseline, 1 month, 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Investigators

  • Principal Investigator: Nyssa Farrell, MD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 25, 2023

Primary Completion (Actual)

September 16, 2024

Study Completion (Actual)

September 16, 2024

Study Registration Dates

First Submitted

February 9, 2024

First Submitted That Met QC Criteria

February 9, 2024

First Posted (Actual)

February 12, 2024

Study Record Updates

Last Update Posted (Actual)

November 10, 2025

Last Update Submitted That Met QC Criteria

October 25, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202304090

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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