Stellate Ganglion Block for COVID-19-Induced Parosmia

(Stella Trial)

Overseen By Cristian Dihel, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Lawson Health Research Institute

Must not be taking: Blood thinners, Antiplatelet agents

Disqualifiers: Chronic rhinosinusitis, Neurodegenerative disorders, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 2 weeks

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called a stellate ganglion block to help individuals who have lost their sense of smell or experience parosmia after COVID-19. The treatment aims to reset the body's nervous system, which might cause these persistent smell issues. Participants will receive either the actual treatment or a placebo (a harmless saline injection) to determine if there's a real benefit. Individuals who had COVID-19 more than six months ago and now experience parosmia could be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using treatments specifically for olfactory dysfunction or taking blood thinners or antiplatelet agents.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that stellate ganglion blocks (SGB) have treated COVID-19-related issues, including smell problems. In some studies, patients reported improvements in symptoms like smell dysfunction and other long COVID symptoms. Safety data indicates that SGB is generally well-tolerated, with some studies showing modest improvements without major side effects. However, other studies found that SGB was not more effective than a placebo for treating COVID-19-related smell changes, indicating variable effectiveness.

SGB has been used for other conditions, providing some existing safety information. While generally considered safe, like any medical procedure, SGB can carry risks and side effects. Clinical trial participants are usually monitored closely to address any issues. Those considering joining a trial should discuss potential risks and benefits with the trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the stellate ganglion block (SGB) for treating COVID-19-induced parosmia because it offers a unique approach compared to traditional treatments, which often focus on symptom management or olfactory training. Unlike these options, SGB involves an ultrasound-guided injection targeting the stellate ganglion, a nerve cluster in the neck, which may help reset the disrupted olfactory signals causing parosmia. This technique is noteworthy because it could potentially provide quicker relief by addressing the underlying neural interference directly. Additionally, the use of ultrasound guidance ensures precise delivery, potentially increasing the treatment's efficacy and safety.

What evidence suggests that the stellate ganglion block could be an effective treatment for COVID-19-induced parosmia?

This trial will compare the effectiveness of Stellate Ganglion Block (SGB) with a placebo for treating parosmia caused by COVID-19. Research has shown mixed results regarding SGB's effectiveness for this condition. Some studies found SGB no better than a placebo in improving symptoms. However, other reports, including a series of case studies, suggested it might help with smell and other long COVID symptoms. A small initial study showed slight improvements in smell and quality of life for those with ongoing COVID-19-related smell issues. Overall, while promising signs exist, the evidence is not yet strong enough for firm conclusions. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 who had COVID-19 at least six months ago and are now experiencing parosmia. Participants must be able to communicate in English and score at least 15 on the DiSODOR scale. People with a history of smell disorders before COVID, certain medical conditions, or those using treatments for olfactory dysfunction cannot join.

Inclusion Criteria

You need to have a score of at least 15 on the DiSODOR test.

I was diagnosed with COVID-19 over 6 months ago and have experienced changes in my sense of smell.

Ability to read, write, and understand English

Exclusion Criteria

I have no conditions or treatments affecting my sense of smell and can tolerate neck injections.

I do not have severe lung issues, recent heart attack, glaucoma, heart rhythm problems, am not on blood thinners or antiplatelet agents, have no allergy to local anesthetics, and can extend my neck.

I experienced changes in my sense of smell before getting COVID-19.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline assessment including demographic information, Parosmia Olfactory Dysfunction Outcomes Rating (DisODOR), Clinical Global Impression: Severity Scale (CGI-S), University of Pennsylvania Smell Identification Test (UPSIT), Long-COVID Questionnaire (LCQ), Olfaction Catastrophizing Scale (OCS), Hospital Anxiety and Depression Scale (HADS), and Pre-Intervention Expectations

1 day

1 visit (in-person)

Treatment

Participants receive Stellate Ganglion Block with Lidocaine or placebo. The first SGB is performed on the right side, and the second SGB is on the left side 5-10 days after the first SGB

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up assessments at 1, 3, and 12 months

12 months

3 visits (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Stellate Ganglion Block

Trial Overview The study is testing if a Stellate Ganglion Block (SGB) with Lidocaine improves smell function compared to a saline injection in people with long-term smell issues after COVID-19. It's a double-blind trial, meaning neither the participants nor the researchers know who gets Lidocaine or placebo.

How Is the Trial Designed?

Group I: Stellate Ganglion Block Experimental Treatment 1 Intervention

The ultrasound-guided stellate ganglion blocks will be performed by a pain management specialist with extensive experience performing these blocks. The first SGB at the initial visit will be performed on the right side, and the second SGB will be on the left side 5-10 days after the first SGB, given that the patient tolerated the first SGB.

Group II: Placebo Group Placebo Group 1 Intervention

The placebo sham injection will be performed in an identical fashion as the stellate ganglion block, with the exception of using 8 mL of 0.9% saline injection instead of Lidocaine.

Who Is Running the Clinical Trial?

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

Published Research Related to This Trial

Stellate ganglion block (SGB) significantly reduced facial pain in patients, with a mean visual analog scale (VAS) score dropping from 8.89 to 0.2 after treatment, and this relief was maintained for at least 12 months.

In contrast, patients who received oral medications (tramadol and gabapentin) showed only a moderate reduction in pain, indicating that early administration of SGB is crucial for optimal efficacy in treating facial pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facial pain: a possible therapy with stellate ganglion block. Salvaggio, I., Adducci, E., Dell'Aquila, L., et al.[2022]

In a study of 195 patients with post-COVID symptoms like parosmia and dysgeusia, 87.4% reported improvement in their sense of smell after receiving a reversible stellate ganglion blockade.

This outpatient treatment shows promising efficacy for alleviating post-COVID symptoms, suggesting it could be a valuable option for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short Communication: Stellate Ganglion Blockade for Persistent Olfactory and Gustatory Symptoms Post-COVID-19. Galvin, V., Cheek, DJ., Zhang, Y., et al.[2023]

Stellate ganglion block (SGB) has been found effective for non-pain indications such as reducing cardiovascular sympathetic stimulation and improving blood flow in limbs, with moderate to low certainty based on 24 studies including 19 randomized controlled trials.

SGB is also recommended for alleviating menopausal symptoms like hot flashes, particularly in cases where conventional treatments have failed, although evidence for other non-pain uses remains insufficient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stellate ganglion block for non-pain indications: a scoping review. Feigin, G., Velasco Figueroa, S., Englesakis, MF., et al.[2023]

Stellate ganglion blocks (SGB) are emerging as a promising adjunctive treatment for various conditions, such as PTSD and long-COVID, by targeting sympathetic hyperactivity through local anesthetic and steroid injections in the cervical area.

The mechanism of action involves reducing nerve growth factor (NGF) and norepinephrine levels, which may help alleviate symptoms in patients who do not respond to traditional medical treatments, although more research is needed to optimize their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Stellate Ganglion Block as an Adjunctive Treatment Modality. Kirkpatrick, K., Khan, MH., Deng, Y., et al.[2023]

In a study of 18 patients with ventricular arrhythmia storm, continuous-infusion stellate ganglion block (SGB) resulted in a 94% reduction in ventricular arrhythmias (VAs) per day, significantly outperforming the 45% reduction seen with single-injection SGB.

Both methods were associated with similar adverse effects, but continuous-infusion SGB required fewer repeat procedures, indicating it may be a more effective and convenient option for managing VAs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stellate Ganglion Blockade With Continuous Infusion Versus Single Injection for Treatment of Ventricular Arrhythmia Storm. Sanghai, S., Abbott, NJ., Dewland, TA., et al.[2021]

Stellate ganglion block (SGB) is a minimally invasive procedure that uses local anesthetics to provide sympathetic nerve block, and its safety has improved significantly with the use of ultrasound guidance, reducing risks like hematoma and nerve injury.

SGB has shown promising therapeutic effects beyond anesthesia, being applied in treating various conditions such as pain, psychological disorders, and endocrine diseases, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of stellate ganglion block in diseases: Its role and application prospect. Deng, JJ., Zhang, CL., Liu, DW., et al.[2023]

Stellate ganglion block (SGB) is emerging as a promising treatment for long COVID symptoms by blocking neuronal transmissions, which may help alleviate issues related to autonomic nervous system dysregulation.

This case report highlights the successful use of SGB in a previously healthy patient, leading to significant improvements in symptoms such as fatigue, post-exertional malaise, shortness of breath, and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stellate Ganglion Block for Long COVID Symptom Management: A Case Report. Khan, MH., Kirkpatrick, KP., Deng, Y., et al.[2023]

Ultrasonographic guidance for stellate ganglion block (SGB) resulted in a complete block in all patients, compared to 11 out of 12 with the blind technique, indicating improved efficacy.

The use of ultrasound significantly reduced complications, as no hematomas occurred with the imaging technique, while three patients experienced hematomas with the blind method, highlighting enhanced safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound imaging for stellate ganglion block: direct visualization of puncture site and local anesthetic spread. A pilot study. Kapral, S., Krafft, P., Gosch, M., et al.[2022]

In a study involving 24 volunteers, the stellate ganglion block (SGB) procedure using lidocaine significantly reduced helper T-cell activation, indicating a temporary depression of immune system activity.

The SGB group showed notable clinical effects, such as Horner's sign and increased temperature in the upper body, while the lidocaine and saline groups did not exhibit these effects, highlighting the specific immunologic impact of SGB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lymphocyte activation is attenuated by stellate ganglion block. Sugimoto, M., Shimaoka, M., Taenaka, N., et al.[2019]

A significant number of individuals recovering from COVID-19 experience Long COVID symptoms, such as fatigue and brain fog, which may be linked to dysautonomia caused by an imbalance in the autonomic nervous system.

In a case series involving two patients, treatment with stellate ganglion block successfully alleviated Long COVID symptoms, suggesting that this approach could be a novel therapeutic option targeting the underlying dysautonomia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stellate ganglion block reduces symptoms of Long COVID: A case series. Liu, LD., Duricka, DL.[2022]

Stellate ganglion block (SGB) can modulate immune system activity by hindering sympathetic innervation to immune organs, leading to reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines, which may alleviate symptoms of various diseases.

The mechanism of SGB's effects likely involves central neuronal pathways connecting the stellate ganglion to brain regions that regulate the autonomic nervous system, suggesting its potential use in treating immune-linked disorders like ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How does stellate ganglion block alleviate immunologically-linked disorders? Lipov, E., Gluncic, V., Lukić, IK., et al.[2021]

In a case series of six patients with long-term COVID-19 symptoms, stellate ganglion block (SGB) was performed under ultrasound guidance, resulting in improvements in olfactory and gustatory functions for most patients.

These findings suggest that SGB could be a promising treatment for olfactory and gustatory dysfunction caused by long-term COVID-19, but further research is necessary to validate the results and determine the best treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Stellate Ganglion Block in Treating Long-Term COVID-19-Related Olfactory and Gustatory Dysfunction: A Case Series. Kalava, A., Benyahia, SA., Tico Calzada, R., et al.[2023]

In a pilot study involving 20 adults with persistent COVID-19-induced olfactory dysfunction, stellate ganglion blocks (SGBs) were found to be safe and resulted in subjective improvements in smell for 50% of participants after one month.

Significant improvements were also observed in smell identification and quality of life related to olfactory function, with 55% of participants showing clinically meaningful gains on the University of Pennsylvania Smell Identification Test, suggesting that SGBs may be a promising treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stellate Ganglion Block for the Treatment of COVID-19-Induced Olfactory Dysfunction: A Prospective Pilot Study. Peterson, AM., Miller, BJ., Kallogjeri, D., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40504522/

Stellate Ganglion Block for the Treatment of COVID-19- ... This randomized clinical trial found that SGB is not superior to placebo in treating COVID-19-induced parosmia, and thus, should not be recommended as ...

2. jamanetwork.com jamanetwork.com/journals/jamaotolaryngology/article-abstract/2834979?mtm_source=25

Stellate Ganglion Block for the Treatment of COVID-19 ... This randomized clinical trial found that SGB is not superior to placebo in treating COVID-19−induced parosmia, and thus, should not be recommended as ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05445921

Stellate Ganglion Block for COVID-19-Induced Olfactory ... The authors concluded that although the sample size is limited, SGB may have a significant impact on the dysautonomia caused by COVID-19 and improve long COVID ...

4. edhub.ama-assn.org edhub.ama-assn.org/jn-learning/audio-player/18994703

Stellate Ganglion Block for the Treatment of COVID-19 ... And that study was our pilot trial where we injected 20 patients who had primarily COVID-induced olfactory loss. So we were really focusing on ...

5. profiles.wustl.edu profiles.wustl.edu/en/publications/stellate-ganglion-block-for-the-treatment-of-covid-19-induced-par

Stellate Ganglion Block for the Treatment of COVID-19- ... Objective: To determine whether stellate ganglion block (SGB) is effective and safe in improving olfactory dysfunction in patients with persistent COVID-19- ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1566070224000493

Reduction of long COVID symptoms after stellate ganglion ... This study suggests that neuromodulation may provide relief of Long COVID symptoms for at least a subset of individuals, and provides support for prospective ...