COVID-19-Induced ParosmiaPhase 2SGBNCT06253806

Stellate Ganglion Block for COVID-induced Parosmia

A Phase 2 study testing Stellate Ganglion Block in people with COVID-19-Induced Parosmia, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 years
Conditions the study is for: COVID-19-Induced Parosmia
What is being tested?: Stellate Ganglion Block
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 48 participants
Where: 1 siteUnited States
Study dates: 25 Oct 2023to 16 Sep 2024
Phase: Phase 2

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 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

History of smell loss or change prior to COVID-19 infection
History of conditions known to impact olfactory dysfunction
Chronic rhinosinusitis
History of prior sinonasal or skull base surgery
Neurodegenerative disorders (Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, Lewy body dementia, frontotemporal dementia)
Currently using concomitant therapies specifically for the treatment of olfactory dysfunction

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Inability to tolerate a needle injection into the neck
History of coexisting conditions that make SGB contraindicated:
Unilateral vocal cord paralysis
Severe COPD (FEV1 between 30-50% of predicted)
Recent myocardial infarction within the last year
Glaucoma
Cardiac conduction block of any degree
Currently taking blood thinners or antiplatelet agents, including aspirin >81mg.
Allergy to local anesthetic
Inability to extend the neck for any reason (e.g., severe arthritis)
History of prior stellate ganglion block

Trial locations and contacts

1 site in 1 country.

United States1 site

Nyssa Fox Farrell
St Louis, Missouri, 63122

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions: COVID-19-Induced Parosmia
Being tested: Stellate Ganglion Block, Placebo Sham Injection
Keywords: COVID-19, Long-COVID, Anosmia, Olfaction Disorders, Pneumonia, Viral, Pneumonia, Respiratory Tract Infections, Infections, Virus Diseases, Coronavirus Infections, Coronaviridae infections, Nidovirales Infections, RNA Virus Infections, Lung Diseases, Respiratory Tract Diseases, Sensation Disorders, Neurologic Manifestations, Nervous System Diseases, Mepivacaine, Anesthetics, local
Medical subject headings: COVID-19, Post-Acute COVID-19 Syndrome, Anosmia, Olfaction Disorders, Pneumonia, Viral, Pneumonia, Respiratory Tract Infections, Infections

What participants receive

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

Stellate Ganglion BlockDrug
Also called mepivacaine
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.
Placebo Sham InjectionDrug
Also called 0.9% saline
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.

Study groups in NCT06253806
Study group	Role	What they receive
Experimental: Stellate Ganglion Block	Active comparator	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. Receives: Drug: Stellate Ganglion Block
Placebo: Sham Injection	Placebo comparator	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. Receives: Drug: Placebo Sham Injection

What is being measured

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

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.
Measured: 1-mo outcome and 3-mo outcome

Secondary outcomes (6)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: during first visit

Timeline

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

25 Oct 202316 Sep 2024

First posted12 Feb 2024
Study start25 Oct 2023
Primary completion16 Sep 2024
Study completion16 Sep 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (37)Papers the sponsor has linked to this study.
Other trials for COVID-19-Induced ParosmiaStudies of the same condition, open and under way.
More trials run by Washington University School of MedicineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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
Masking: Double blind
Who is masked: Participant, Care provider
Enrolment: 48 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06253806
Sponsor's protocol ID: 202304090
Acronym: SGB
Status last verified: Oct 2025
First submitted: 9 Feb 2024
Last updated: 10 Nov 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Hintschich CA, Fischer R, Hummel T, Wenzel JJ, Bohr C, Vielsmeier V. Persisting olfactory dysfunction in post-COVID-19 is associated with gustatory impairment: Results from chemosensitive testing eight months after the acute infection. PLoS One. 2022 Mar 23;17(3):e0265686. doi: 10.1371/journal.pone.0265686. eCollection 2022.
PubMed 35320821
Fortunato F, Martinelli D, Iannelli G, Milazzo M, Farina U, Di Matteo G, De Nittis R, Ascatigno L, Cassano M, Lopalco PL, Prato R. Self-reported olfactory and gustatory dysfunctions in COVID-19 patients: a 1-year follow-up study in Foggia district, Italy. BMC Infect Dis. 2022 Jan 22;22(1):77. doi: 10.1186/s12879-022-07052-8.
PubMed 35065619
Khan AM, Kallogjeri D, Piccirillo JF. Growing Public Health Concern of COVID-19 Chronic Olfactory Dysfunction. JAMA Otolaryngol Head Neck Surg. 2022 Jan 1;148(1):81-82. doi: 10.1001/jamaoto.2021.3379.
PubMed 34792577
Lerner DK, Garvey KL, Arrighi-Allisan AE, Filimonov A, Filip P, Shah J, Tweel B, Del Signore A, Schaberg M, Colley P, Govindaraj S, Iloreta AM. Clinical Features of Parosmia Associated With COVID-19 Infection. Laryngoscope. 2022 Mar;132(3):633-639. doi: 10.1002/lary.29982. Epub 2021 Dec 13.
PubMed 34870334
Schambeck SE, Crowell CS, Wagner KI, D'Ippolito E, Burrell T, Mijocevic H, Protzer U, Busch DH, Gerhard M, Poppert H, Beyer H. Phantosmia, Parosmia, and Dysgeusia Are Prolonged and Late-Onset Symptoms of COVID-19. J Clin Med. 2021 Nov 12;10(22):5266. doi: 10.3390/jcm10225266.
PubMed 34830550
Hopkins C, Surda P, Vaira LA, Lechien JR, Safarian M, Saussez S, Kumar N. Six month follow-up of self-reported loss of smell during the COVID-19 pandemic. Rhinology. 2021 Feb 1;59(1):26-31. doi: 10.4193/Rhin20.544.
PubMed 33320115
Keller A, Malaspina D. Hidden consequences of olfactory dysfunction: a patient report series. BMC Ear Nose Throat Disord. 2013 Jul 23;13(1):8. doi: 10.1186/1472-6815-13-8.
PubMed 23875929
Santos DV, Reiter ER, DiNardo LJ, Costanzo RM. Hazardous events associated with impaired olfactory function. Arch Otolaryngol Head Neck Surg. 2004 Mar;130(3):317-9. doi: 10.1001/archotol.130.3.317.
PubMed 15023839
Pang NY, Song HJJMD, Tan BKJ, Tan JX, Chen ASR, See A, Xu S, Charn TC, Teo NWY. Association of Olfactory Impairment With All-Cause Mortality: A Systematic Review and Meta-analysis. JAMA Otolaryngol Head Neck Surg. 2022 May 1;148(5):436-445. doi: 10.1001/jamaoto.2022.0263.
PubMed 35389456
Addison AB, Wong B, Ahmed T, Macchi A, Konstantinidis I, Huart C, Frasnelli J, Fjaeldstad AW, Ramakrishnan VR, Rombaux P, Whitcroft KL, Holbrook EH, Poletti SC, Hsieh JW, Landis BN, Boardman J, Welge-Lussen A, Maru D, Hummel T, Philpott CM. Clinical Olfactory Working Group consensus statement on the treatment of postinfectious olfactory dysfunction. J Allergy Clin Immunol. 2021 May;147(5):1704-1719. doi: 10.1016/j.jaci.2020.12.641. Epub 2021 Jan 13.
PubMed 33453291
Lee JJ, Peterson AM, Kallogjeri D, Jiramongkolchai P, Kukuljan S, Schneider JS, Klatt-Cromwell CN, Drescher AJ, Brunworth JD, Piccirillo JF. Smell Changes and Efficacy of Nasal Theophylline (SCENT) irrigation: A randomized controlled trial for treatment of post-viral olfactory dysfunction. Am J Otolaryngol. 2022 Mar-Apr;43(2):103299. doi: 10.1016/j.amjoto.2021.103299. Epub 2021 Dec 3.
PubMed 34894449
Reden J, Lill K, Zahnert T, Haehner A, Hummel T. Olfactory function in patients with postinfectious and posttraumatic smell disorders before and after treatment with vitamin A: a double-blind, placebo-controlled, randomized clinical trial. Laryngoscope. 2012 Sep;122(9):1906-9. doi: 10.1002/lary.23405. Epub 2012 Jul 2.
PubMed 22752966
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
Patel ZM, Holbrook EH, Turner JH, Adappa ND, Albers MW, Altundag A, Appenzeller S, Costanzo RM, Croy I, Davis GE, Dehgani-Mobaraki P, Doty RL, Duffy VB, Goldstein BJ, Gudis DA, Haehner A, Higgins TS, Hopkins C, Huart C, Hummel T, Jitaroon K, Kern RC, Khanwalkar AR, Kobayashi M, Kondo K, Lane AP, Lechner M, Leopold DA, Levy JM, Marmura MJ, Mclelland L, Miwa T, Moberg PJ, Mueller CA, Nigwekar SU, O'Brien EK, Paunescu TG, Pellegrino R, Philpott C, Pinto JM, Reiter ER, Roalf DR, Rowan NR, Schlosser RJ, Schwob J, Seiden AM, Smith TL, Soler ZM, Sowerby L, Tan BK, Thamboo A, Wrobel B, Yan CH. International consensus statement on allergy and rhinology: Olfaction. Int Forum Allergy Rhinol. 2022 Apr;12(4):327-680. doi: 10.1002/alr.22929.
PubMed 35373533
Rezaeian A. Effect of Intranasal Insulin on Olfactory Recovery in Patients with Hyposmia: A Randomized Clinical Trial. Otolaryngol Head Neck Surg. 2018 Jun;158(6):1134-1139. doi: 10.1177/0194599818764624. Epub 2018 Mar 20.
PubMed 29557250