Stellate Ganglion Block for COVID-induced Parosmia

NCT06253806 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 202304090
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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 Recent research by our group (unpublished data) and suggests that parosmias, moreso than hyposmias, can result in increased rates of anxiety, depression, and even suicidal ideation.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

Conditions

COVID-19-Induced Parosmia

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; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents; Stellate Ganglion Block

Outcome Measures

Primary Outcomes (1)

• 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.

  1-mo outcome and 3-mo outcome

Secondary Outcomes (6)

• Clinical Global Impression - Severity Scale (CGI-S) Smell Loss

  1-mo and 3-mo

• Long-COVID Questionnaire

  1 month, 3 months

• Olfaction Catastrophizing Scale (OCS)

  1 month, 3 months

• Hospital Anxiety and Depression Scale (HADS)

  1 month, 3 months

• Patient Satisfaction With Treatment

  1 mo, 3-mo

Other Outcomes (1)

• Adverse Events Assessment

  Baseline, 1 month, 3 months

Study Arms (2)

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.

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.

Drug: Placebo Sham Injection

Interventions

Stellate Ganglion Block DRUG

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

Experimental: Stellate Ganglion Block

Placebo Sham Injection DRUG

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

Placebo: Sham Injection

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Nyssa Fox Farrell

St Louis, Missouri, 63122, United States

Location

Related Publications (37)

• 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.

  PMID: 35320821 BACKGROUND

• 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.

  PMID: 35065619 BACKGROUND

• 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.

  PMID: 34792577 BACKGROUND

• 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.

  PMID: 34870334 BACKGROUND

• 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.

  PMID: 34830550 BACKGROUND

• 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.

  PMID: 33320115 BACKGROUND

• 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.

  PMID: 23875929 BACKGROUND

• 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.

  PMID: 15023839 BACKGROUND

• 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.

  PMID: 35389456 BACKGROUND

• 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.

  PMID: 33453291 BACKGROUND

• 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.

  PMID: 34894449 BACKGROUND

• 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.

  PMID: 22752966 BACKGROUND

• 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.

  PMID: 33471169 BACKGROUND

• 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.

  PMID: 35373533 BACKGROUND

• 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.

  PMID: 29557250 BACKGROUND

• Kang CK, Oh ST, Chung RK, Lee H, Park CA, Kim YB, Yoo JH, Kim DY, Cho ZH. Effect of stellate ganglion block on the cerebrovascular system: magnetic resonance angiography study. Anesthesiology. 2010 Oct;113(4):936-44. doi: 10.1097/ALN.0b013e3181ec63f5.

  PMID: 20823762 BACKGROUND

• Treggiari MM, Romand JA, Martin JB, Reverdin A, Rufenacht DA, de Tribolet N. Cervical sympathetic block to reverse delayed ischemic neurological deficits after aneurysmal subarachnoid hemorrhage. Stroke. 2003 Apr;34(4):961-7. doi: 10.1161/01.STR.0000060893.72098.80. Epub 2003 Mar 20.

  PMID: 12649526 BACKGROUND

• Mulvaney SW, McLean B, de Leeuw J. The use of stellate ganglion block in the treatment of panic/anxiety symptoms with combat-related post-traumatic stress disorder; preliminary results of long-term follow-up: a case series. Pain Pract. 2010 Jul-Aug;10(4):359-65. doi: 10.1111/j.1533-2500.2010.00373.x. Epub 2010 Apr 20.

  PMID: 20412504 BACKGROUND

• Lipov EG, Joshi JR, Sanders S, Slavin KV. A unifying theory linking the prolonged efficacy of the stellate ganglion block for the treatment of chronic regional pain syndrome (CRPS), hot flashes, and posttraumatic stress disorder (PTSD). Med Hypotheses. 2009 Jun;72(6):657-61. doi: 10.1016/j.mehy.2009.01.009. Epub 2009 Feb 23.

  PMID: 19237252 BACKGROUND

• Rae Olmsted KL, Bartoszek M, Mulvaney S, McLean B, Turabi A, Young R, Kim E, Vandermaas-Peeler R, Morgan JK, Constantinescu O, Kane S, Nguyen C, Hirsch S, Munoz B, Wallace D, Croxford J, Lynch JH, White R, Walters BB. Effect of Stellate Ganglion Block Treatment on Posttraumatic Stress Disorder Symptoms: A Randomized Clinical Trial. JAMA Psychiatry. 2020 Feb 1;77(2):130-138. doi: 10.1001/jamapsychiatry.2019.3474.

  PMID: 31693083 BACKGROUND

• Hou J, Pu S, Xu X, Lu Z, Wu J. Real-time ultrasound-guided stellate ganglion block for migraine: an observational study. BMC Anesthesiol. 2022 Mar 24;22(1):78. doi: 10.1186/s12871-022-01622-8.

  PMID: 35331152 BACKGROUND

• Yucel I, Demiraran Y, Ozturan K, Degirmenci E. Complex regional pain syndrome type I: efficacy of stellate ganglion blockade. J Orthop Traumatol. 2009 Dec;10(4):179-83. doi: 10.1007/s10195-009-0071-5. Epub 2009 Nov 4.

  PMID: 19888550 BACKGROUND

• Liao CD, Tsauo JY, Liou TH, Chen HC, Rau CL. Efficacy of Noninvasive Stellate Ganglion Blockade Performed Using Physical Agent Modalities in Patients with Sympathetic Hyperactivity-Associated Disorders: A Systematic Review and Meta-Analysis. PLoS One. 2016 Dec 2;11(12):e0167476. doi: 10.1371/journal.pone.0167476. eCollection 2016.

  PMID: 27911934 BACKGROUND

• Fischer L, Barop H, Ludin SM, Schaible HG. Regulation of acute reflectory hyperinflammation in viral and other diseases by means of stellate ganglion block. A conceptual view with a focus on Covid-19. Auton Neurosci. 2022 Jan;237:102903. doi: 10.1016/j.autneu.2021.102903. Epub 2021 Nov 10.

  PMID: 34894589 BACKGROUND

• Lee NS, Yoon HR, Park JW, Yum JH, Seo JH, Cho JH, et al. The efficacy of stellate ganglion block in olfactory disorder following upper respiratory tract infection. Korean J Otolaryngol-Head Neck Surg. 2003;46:568-571.

  BACKGROUND

• Moon HS, Lee HJ, Sung CH, Lim SJ, Choi JH. The efficacy of stellate ganglion block in sensorineural anosmia patients unresponsive to steroid therapy. Korean J Pain. 2007;20:154-157

  BACKGROUND

• Moon HS, Chon JY, Lee SH, Ju YM, Sung CH. Long-term Results of Stellate Ganglion Block in Patients with Olfactory Dysfunction. Korean J Pain. 2013 Jan;26(1):57-61. doi: 10.3344/kjp.2013.26.1.57. Epub 2013 Jan 4.

  PMID: 23342209 BACKGROUND

• Chauhan G, Upadhyay A, Khanduja S, Emerick T. Stellate Ganglion Block for Anosmia and Dysgeusia Due to Long COVID. Cureus. 2022 Aug 8;14(8):e27779. doi: 10.7759/cureus.27779. eCollection 2022 Aug.

  PMID: 36106285 BACKGROUND

• Liu LD, Duricka DL. Stellate ganglion block reduces symptoms of Long COVID: A case series. J Neuroimmunol. 2022 Jan 15;362:577784. doi: 10.1016/j.jneuroim.2021.577784. Epub 2021 Dec 8.

  PMID: 34922127 BACKGROUND

• Khan MH, Kirkpatrick KP, Deng Y, Shah KB. Stellate Ganglion Block for Long COVID Symptom Management: A Case Report. Cureus. 2022 Dec 7;14(12):e32295. doi: 10.7759/cureus.32295. eCollection 2022 Dec.

  PMID: 36628048 BACKGROUND

• Galvin V, Cheek DJ, Zhang Y, Collins G, Gaskin D. Short Communication: Stellate Ganglion Blockade for Persistent Olfactory and Gustatory Symptoms Post-COVID-19. Local Reg Anesth. 2023 May 3;16:25-30. doi: 10.2147/LRA.S402197. eCollection 2023.

  PMID: 37162813 BACKGROUND

• Dunlop BW, Gray J, Rapaport MH. Transdiagnostic Clinical Global Impression Scoring for Routine Clinical Settings. Behav Sci (Basel). 2017 Jun 27;7(3):40. doi: 10.3390/bs7030040.

  PMID: 28653978 BACKGROUND

• Doty RL, Shaman P, Dann M. Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav. 1984 Mar;32(3):489-502. doi: 10.1016/0031-9384(84)90269-5.

  PMID: 6463130 BACKGROUND

• Doty RL. Office procedures for quantitative assessment of olfactory function. Am J Rhinol. 2007 Jul-Aug;21(4):460-73. doi: 10.2500/ajr.2007.21.3043.

  PMID: 17882917 BACKGROUND

• Hughes SE, Haroon S, Subramanian A, McMullan C, Aiyegbusi OL, Turner GM, Jackson L, Davies EH, Frost C, McNamara G, Price G, Matthews K, Camaradou J, Ormerod J, Walker A, Calvert MJ. Development and validation of the symptom burden questionnaire for long covid (SBQ-LC): Rasch analysis. BMJ. 2022 Apr 27;377:e070230. doi: 10.1136/bmj-2022-070230.

  PMID: 35477524 BACKGROUND

• McLean B. Safety and Patient Acceptability of Stellate Ganglion Blockade as a Treatment Adjunct for Combat-Related Post-Traumatic Stress Disorder: A Quality Assurance Initiative. Cureus. 2015 Sep 10;7(9):e320. doi: 10.7759/cureus.320.

  PMID: 26487996 BACKGROUND

• Farrell NF, Crock LW, Islam A, Adkins D, Peterson AM, Kallogjeri D, Piccirillo JF. Stellate Ganglion Block for the Treatment of COVID-19-Induced Parosmia: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2025 Aug 1;151(8):741-749. doi: 10.1001/jamaoto.2025.1304.

  PMID: 40504522 DERIVED

MeSH Terms

Conditions

COVID-19; Post-Acute COVID-19 Syndrome; 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

Interventions

Mepivacaine; Saline Solution

Condition Hierarchy (Ancestors)

Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

Limitations include lack of objective assessment for parosmia, which remains poorly defined in the literature.

Results Point of Contact

• Title: Nyssa Farrell, MD
• Organization: Washington University, Department of Otolaryngology - Head and Neck Surgery

nyssafarrell@wustl.edu

314-273-2490

Study Officials

• Nyssa Farrell, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2024
• First Posted: February 12, 2024
• Study Start: October 25, 2023
• Primary Completion: September 16, 2024
• Study Completion: September 16, 2024
• Last Updated: November 10, 2025
• Results First Posted: November 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)