Efficacy of Gabapentin for Post-Covid-19 Olfactory Dysfunction

Study Overview
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Brief Summary
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This study will investigate the efficacy of oral gabapentin in olfactory improvement following Covid-19- associated olfactory dysfunction. This is a randomized, double-blinded, placebo-controlled trial.

Detailed Description
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The drug will be given over a maximum 14 weeks with up to four weeks titrating up, eight weeks maintaining highest tolerable dose, and up to two weeks tapering down. Change in olfactory function from baseline to completion of 8-week fixed-dose period will be compared between the two study groups. Follow-up assessments will be conducted for both groups 4 weeks after completion of taper down.

Official Title
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Efficacy of Gabapentin for Post-Covid-19 Olfactory Dysfunction

Conditions
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COVID-19, Olfactory Disorder, Anosmia, Hyposmia, Parosmia

Intervention / Treatment
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* Drug: Gabapentin gelatin capsules 300mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women between the ages of 18 and 65 years Residing within the states of Missouri or Illinois Clinically diagnosed or subjective olfactory dysfunction (anosmia, hyposmia, or parosmia) of 3 months duration or longer diagnosed within 2 weeks of Covid-19 infection UPSIT score consistent with diminished olfactory function (score ≤ 33 in men and ≤ 34 in women). Willing to respond daily to study surveys, preferably through smartphone with unlimited texting plan In possession of ALL 7 household items: soap, burnt candle, peanut butter, herb, garlic, lemon, and coffee Exclusion Criteria: Clinically diagnosed olfactory dysfunction secondary to genetic abnormalities or congenital dysfunction, trauma, non-Covid-19 viral infection, nasal polyps, neurodegenerative disorders Current use of: azelastine, bromperidol, orophenadrine, oxomemazine, kratom, paraldehyde, or thalidomide History of addiction to alcohol, cocaine, or opioids Impaired renal function, myasthenia gravis, or myoclonus Severe allergy to peanuts Pregnancy or attempting pregnancy during study participation Inability to participate in virtual trial due to lack of access to the internet or unlimited text messaging; inability to comprehend or use English language Availability less than 6 months from time of enrollment Residency in states other than Missouri or Illinois.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blinded, randomized, placebo-controlled trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gabapentin<br>This arm will be given the active treatment, oral Letco (gabapentin) gelatin capsules of 300mg each. Up to the first four weeks will be a titration period (week 1 300mg TID, week 2 600mg TID, week 3 900mg TID, week 4 1,200mg TID) as tolerated. If intolerable adverse reactions occur, the dosage will be decreased to prior tolerable dose (e.g., if 900mg TID is intolerable, dose will be decreased to 600mg TID). The following eight weeks will be fixed dose, the highest tolerable dose from the titration period. Up to two weeks will be a taper down tailored to the maximum dose the participant reached during the titration and fixed periods. A maximum 14 weeks will mark the end of active treatment. Follow-up assessments will be conducted 4 weeks after completion of the taper-down period. | Drug: Gabapentin gelatin capsules 300mg<br>* Gabapentin is an anti-epileptic also used for nerve pain. This study will investigate the efficacy of gabapentin for olfactory nerve recovery and improvement in post-Covid-19 olfactory dysfunction.<br>* Other names: Letco;|
| Placebo Comparator: Placebo<br>Placebo gelatin capsules that look, smell, and taste like gabapentin capsules will be given to the placebo arm. To preserve double-blinding of the study, subjects will receive one capsule TID the first week, the second week two capsules TID, the third week three capsules TID, and fourth week four capsules TID as tolerated. If intolerable, the dose will be decreased to prior tolerable dose. The next eight weeks will be a fixed amount of placebo based on the highest tolerable amount from the titration period. Subjects will then taper-down placebo to imitate the gabapentin arm for maximum two weeks based on highest dose achieved during study. 4 weeks after completion of taper-down, follow-up assessments will be conducted. | Drug: Placebo<br>* lactose monohydrate NF<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression of Improvement Scale (CGI-I) | The CGI-Severity scale ranges from 1 to 7, where 1 is Very Much Improved and 7 is Very Much Worsened. This assessment will provide subjective data on patients' change in olfaction from baseline. Participants reporting 3 as Minimally Improved, 2 as Much Improved, or 1 as Very Much Improved in the CGI-I will be deemed responders to treatment, and the number of responders to non-responders will be compared between the two arms | After completion of eight-week fixed-dose period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| University of Pennsylvania Smell Identification Test (UPSIT) | The UPSIT is composed of 40 strips of microencapsulated odorants, which are present on the bottom of each page, just below a four-alternative multiple-choice question. For a given item, the patient releases an odor by scratching the microencapsulated pad with a pencil tip, smells the pad, and indicates the odor quality from four alternatives. Even if no smell is perceived, a response is required (i.e., the test is forced-choice). The subject's total correct score out of the 40 items is determined and provides an objective measure of olfactory function. | Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period | 
| Olfactory Dysfunction Outcomes Rating (ODOR) | The ODOR questionnaire is a 28-item disease-specific health status survey to assess the physical problems, functional impairments, and emotional consequences secondary to olfactory dysfunction. ODOR was developed and validated by Dr. Jake Lee and colleagues in the Clinical Outcomes Research Office at Washington University | Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period | 
| NASAL-7 | NASAL-7 is a simple diagnostic tool for olfactory dysfunction that is based on commonly found household items and can be used by adults who suspect olfactory dysfunction. The NASAL-7, contains 7 household items with each item scored as 0 for 'Cannot Smell', 1 for 'Smells Less Strong/Different Than Normal', and 2 for 'Smells Normal', for a total possible score ranging from 0-14. The following four categories of olfactory function were defined based on NASAL-7 score: anosmia (score 0-4), severe dysfunction (score 5-7), mild dysfunction (score 8-10), and normosmia (score 11-14). | Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period | 
| Clinical Global Impression - Severity Scale for Parosmics (CGI-P) | The CGI-P Scale is a global rating of parosmia and the single global rating ranges from 1-5, where 1 is No Distortion, 2 is Mild Distortion, 3 is Moderate Distortion, 4 is Mostly Distorted, and 5 is Complete Distortion. The response on the CGI-P will provide information on the patient's perceived severity of the distortion of their smell. | Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period | 
| Clinical Global Impression of Severity Scale (CGI-S) | The CGI-S Scale is a subjective rating of severity which ranges from 1 - 7 (1 is normal function and 7 is complete anosmia) to measure severity of smell loss. | Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period | 
| Clinical Global Impression of Improvement Scale (CGI-I) | The CGI-Severity scale ranges from 1 to 7, where 1 is Very Much Improved and 7 is Very Much Worsened. This assessment will provide subjective data on patients' change in olfaction from baseline. | 4 weeks after completion of Taper-Down Period. |