Stellate Ganglion Block With Lidocaine for the Treatment of COVID-19-Induced Parosmia

Sponsor

Lawson Health Research Institute (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06055270

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Chronic olfactory dysfunction, both hyposmia and parosmia, from the COVID-19 pandemic is a growing public health crisis, affecting up to 1.2 million people in the United States. Olfactory dysfunction significantly impacts one's quality of life by decreasing the enjoyment of foods, creating environmental safety concerns, and affecting one's ability to perform specific jobs. Olfactory loss is also an independent predictor of anxiety, depression, and mortality.

Recent research suggests that parosmia, more so than hyposmia, can increase anxiety, depression, and even suicidal ideation. While the pandemic has advanced the scientific community's interest 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 result from sympathetic nervous system dysfunction. 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 before 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 in 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 with Lidocaine versus saline injection in up to 50 participants with persistent COVID-19-associated olfactory dysfunction.

Condition or Disease	Intervention/Treatment	Phase
Parosmia	Procedure: Stellate Ganglion Block Other: Placebo	Phase 3

Detailed Description

This will be a double-blinded, placebo-controlled, randomized clinical to assess the efficacy of Stellate Ganglion Block with Lidocaine 1% (8mL). Participants with parosmia will be randomly assigned to SGB with Lidocaine 1% (8mL) or Placebo (saline solution). Baseline assessment will happen in person and will consist on 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), Pre-Intervention Expectations. Then, after the assigned interventional procedures are performed three remote visits will be performed as follow-ups (1, 3, and 12 months), in which the variables above will be reassessed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

44 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double-Blinded, Placebo-Controlled Randomized Clinical TrialDouble-Blinded, Placebo-Controlled Randomized Clinical Trial

Masking:

Double (Participant, Investigator)

Masking Description:

Study statistician

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jan 15, 2024

Anticipated Primary Completion Date :

Dec 24, 2025

Anticipated Study Completion Date :

May 15, 2026

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Group 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.	Other: Placebo 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 Other Names: Placebo sham injection
Experimental: Stellate Ganglion Block 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.	Procedure: Stellate Ganglion Block All SGBs will be performed by a board-certified anesthesiologist and pain management specialist with extensive experience performing SGBs. The laterality of the SGB will be randomized between the left and right sides of the neck. Participants will be asked to abstain from eating and drinking for 8 hours prior to the SGB. Using ultrasound guidance, the transverse process of the C6 vertebra is identified. Color-doppler is used to identify blood vessels. A 27-gauge needle is used to anesthetize the superficial skin with 1% lidocaine. Then, a 21-gauge ultrasound needle is advanced using an in-plane technique from lateral to medial with careful avoidance of neurovascular structures. After negative aspiration, 8 mL of 1% Lidocaine is deposited beneath the prevertebral fascia and above the Longus coli muscle into the stellate ganglion. Other Names: SGB sympathetic block

Arm

Intervention/Treatment

Placebo Comparator: Placebo Group

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.

Other: Placebo

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

Other Names:

Placebo sham injection

Experimental: Stellate Ganglion Block

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.

Procedure: Stellate Ganglion Block

All SGBs will be performed by a board-certified anesthesiologist and pain management specialist with extensive experience performing SGBs. The laterality of the SGB will be randomized between the left and right sides of the neck. Participants will be asked to abstain from eating and drinking for 8 hours prior to the SGB. Using ultrasound guidance, the transverse process of the C6 vertebra is identified. Color-doppler is used to identify blood vessels. A 27-gauge needle is used to anesthetize the superficial skin with 1% lidocaine. Then, a 21-gauge ultrasound needle is advanced using an in-plane technique from lateral to medial with careful avoidance of neurovascular structures. After negative aspiration, 8 mL of 1% Lidocaine is deposited beneath the prevertebral fascia and above the Longus coli muscle into the stellate ganglion.

Other Names:

SGB

sympathetic block

Outcome Measures

Primary Outcome Measures

Parosmia Olfactory Dysfunction Outcomes Rating (DisODOR) [Baseline, 1, 3, and 12 months after SGB]
The DisODOR is a disease-specific questionnaire that assesses for physical problems, functional limitations, and emotional consequences of parosmia secondary to any etiology. The instrument contains 29 total items with each scored on a 5-point Likert scale from 0 to 4. The minimal clinically important difference (MCID) for the instrument is 15.

Secondary Outcome Measures

Clinical Global Impression - Severity Scale (CGI-S) [Baseline]
The baseline severity of parosmia will be measured with the CGI-S scale. The CGI-S scale measures disease severity in clinical condition based on a 5-point Likert scale.
Clinical Global Impression - Improvement Scale (CGI-I) [1, 3, and 12 months after SGB]
The overall response to treatment will be measured with the CGI-I scale. The CGI-I Scale measures response to treatment for a number of disorders and has good internal consistency and validity.32 The CGI-I scale measures change in clinical condition based on a 7-point Likert scale. The CGI-I for parosmia asks, "Compared to before your stellate ganglion block, how would you describe your parosmia (things do not smell the same as you remember)?" Response options for each are: (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. Responders are defined as those who report "slightly better now than before" or greater.
University of Pennsylvania Smell Identification Test (UPSIT, Sensonics, New Jersey). [Baseline]
The UPSIT is a test of olfactory identification and consists of four 10-page booklets, with a total of 40 items. On each page, there is a different "scratch and sniff" strip and four choice options. Subjects are asked to scratch each strip with a pencil to release the scents, detect the smell, and identify the smell from the four choice options. The UPSIT comes from a scoring rubric that identifies the normalcy benchmark based on age and gender, which is >34 in women and >33 in men.33,34 The UPSIT is commercially available, takes 10-15 minutes to complete, and is the gold standard test to assess smell identification. The minimal clinically important difference of the UPSIT is 4.
Long-COVID Questionnaire (LCQ) [Baseline, 1, 3, and 12 months after SGB]
Symptoms assessed via the LCQ are derived from the Symptom Burden Questionnaire for Long Covid35, which included tiredness/fatigue, shortness of breath, brain fogginess, headache, cough, depression, low-grade fevers, palpitations, dizziness, muscle pain, and joint pains. At baseline, participants are asked to rank the current severity of each problem on a 5-point Likert scale. 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.
Olfaction Catastrophizing Scale (OCS) [Baseline, 1, 3, and 12 months after SGB]
The pain catastrophizing scale (PCS) was developed to measure the negative mental response to actual or anticipated pain. The OCS was derived from the validated PCS to similarly measure 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. At each visit, subjects will be asked to complete the OCS.
Hospital Anxiety and Depression Scale (HADS) [Baseline, 1, 3, and 12 months after SGB]
The HADS was developed for screen for 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. Subjects will be screened for anxiety and depression on their initial visit.
Pre-Intervention Expectations [Baseline]
A significant number of social media and news stories have discussed anecdotal success of stellate ganglion blocks for COVID-19-induced olfactory dysfunction. As a result, we propose that participants may have a distorted pre-operative expectation that may affect their subjective rating of improvement in olfaction. Therefore, participants will be asked at baseline, "How confident are you that the stellate ganglion block will improve your smell loss or smell distortion?" Possible answer choices: Not at all, Slightly confident, Somewhat confident, Very confident, Extremely confident.
Patient Satisfaction with Treatment [1, 3, and 12 months after SGB]
Participants will be asked at the 1-month virtual visit, "Overall, how satisfied were you with the stellate ganglion block treatment for your parosmia?" 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. Patients will also be asked at the final visit, "Would you recommend this treatment to a family member or close friend who also suffers from chronic smell loss due to COVID-19?" Possible answer choices: 1) Yes, 2) No.
Assessment of the Blind [1 Month after SGB]
Immediately after the initial injection, participants will be asked, "Which intervention do you think you received?" Answer choices: 1)Lidocaine (active medication) 2) Saline (placebo).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults age 18 to 70
Diagnosis of COVID-19 at least 6 months prior to study enrollment with self-reported parosmia
Ability to read, write, and understand English
Score of at least 15 on DiSODOR

Exclusion Criteria:

History of smell loss or change prior to COVID-19 infection
History of conditions known to impact olfactory function:
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 chronic obstructive pulmonary disease (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
Allergy to local anesthetic
Inability to extend the neck for any reason (e.g., severe arthritis)