Efficacy of Gabapentin for Post-Covid-19 Olfactory Dysfunction (GRACE)

February 11, 2025 updated by: Washington University School of Medicine
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

68

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Gabapentin

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
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.
Other Names:
  • Letco
Placebo Comparator: 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.
Drug: Placebo
lactose monohydrate NF

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Global Impression of Improvement Scale (CGI-I)
Time Frame: 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
After the 8 week FD phase and four week post-tapper

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
University of Pennsylvania Smell Identification Test (UPSIT)
Time Frame: 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)
Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period
Olfactory Dysfunction Outcomes Rating (ODOR)
Time Frame: 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.
Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period
NASAL-7
Time Frame: 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).
Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period
CGI-Severity of Smell
Time Frame: 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
8-week Fixed-Dose period, and 4 weeks after completion of Taper-Down phase
CGI-S of Parosmia
Time Frame: 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.
8-week Fixed-Dose period, and 4 weeks after completion of Taper-Down phase

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Investigators

  • Principal Investigator: Jay F Piccirillo, MD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 10, 2022

Primary Completion (Actual)

August 29, 2023

Study Completion (Actual)

August 29, 2023

Study Registration Dates

First Submitted

January 6, 2022

First Submitted That Met QC Criteria

January 6, 2022

First Posted (Actual)

January 11, 2022

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 11, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202110011

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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