Efficacy of Gabapentin for Post-Covid-19 Olfactory Dysfunction

Phase 2

Completed

Conditions: Olfactory Disorder
Anosmia
Hyposmia
COVID-19
Parosmia

Interventions: Drug: Gabapentin gelatin capsules 300mg
Drug: Placebo

Registration Number: NCT05184192

Lead Sponsor: Washington University School of Medicine

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 68

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Gabapentin	Gabapentin gelatin capsules 300mg	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.
Placebo	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Clinical Global Impression of Improvement Scale (CGI-I)	After the 8 week FD phase and four week post-tapper	The primary outcome measure was the treatment response rate following the 8-week FD phase as determined by the CGI-I. The CGI-I is a modified 7-point Likert scale of -perceived change. Response options include: (1) much better, (2) somewhat better, (3) slightly better), (4) neither better nor worse, (5) slightly worse, (6) somewhat worse, (7) much worse. The response rate was defined as the number of participants self-reporting at least "slightly better" divided by the number of participants in each treatment group. Th

Secondary Outcome Measures

Name	Time	Method
University of Pennsylvania Smell Identification Test (UPSIT)	Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period	Forty different odors are presented in this test. Scoring: Forced choice of 4 responses to identify each smell. Anosmia: score 6-18; severe microsmia: score 19-25, moderate microsmia: 26-30 in women and 26-29 in men; mild microsmia: 31-34 in women and 30-33 in men; and normosmia: score \> 34 in women and \>33 in men. The total UPSIT score can range from 0 to 40 and scores. The MCID in UPSIT score is 4. Scores are interpreted as the level of absolute smell function (i.e., normosmia, mild hyposmia, moderate hyposmia, severe hyposmia, and anosmia), using the age- and sex-related normative classification system described in the UPSIT manual (Table 1)
Olfactory Dysfunction Outcomes Rating (ODOR)	Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period	The ODOR questionnaire is a validated 28-item patient-reported outcome measure which assesses the physical, functional, and emotional consequences of OD. The ODOR is a 28-item instrument with each item scored as either no difficulty or very rarely bothered (0) to complete difficulty or very frequently bothered (4) with a total instrument score range of 0 to 112 points. Higher scores indicate higher degree of dysfunction and limitation. the MCID is 15 points.
NASAL-7	Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period	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 was developed by Dr. Piccirillo and colleagues in the Clinical Outcomes Research Office. 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).
CGI-Severity of Smell	8-week Fixed-Dose period, and 4 weeks after completion of Taper-Down phase	CGI-Severity. The CGI-Severity scale ranges from 1 to 7, where 1 is normal function and 7 is complete anosmia. This assessment will provide subjective data on patients' baseline olfactory function prior to beginning the trial, after 8-week Fixed-Dose period, and 4 weeks after completion of Taper-Down phase
CGI-S of Parosmia	8-week Fixed-Dose period, and 4 weeks after completion of Taper-Down phase	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.