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NCT05184192: GRACE

Efficacy of Gabapentin for Post-Covid-19 Olfactory Dysfunction

Completed Phase 2 Results posted Last updated 4 March 2025
What this trial tests

Phase 2 trial testing Gabapentin gelatin capsules 300mg in COVID-19 in 68 participants. Completed in 29 August 2023.

Timeline
10 January 2022
Primary endpoint
29 August 2023
29 August 2023

Quick facts

Lead sponsorWashington University School of Medicine
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment68
Start date10 January 2022
Primary completion29 August 2023
Estimated completion29 August 2023
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Washington University School of Medicine

Who can join

Adults 18 to 65, any sex, with COVID-19 or Olfactory Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Clinical Global Impression of Improvement Scale (CGI-I) Primary · 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

Fixed Dose Period
GroupValue95% CI
Gabapentin8
Placebo20
4 week post tapper
GroupValue95% CI
Gabapentin7
Placebo12
University of Pennsylvania Smell Identification Test (UPSIT) Secondary · 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 clas

Baseline
GroupValue95% CI
Gabapentin2310 – 31
Placebo247 – 34
Fixed Dose
GroupValue95% CI
Gabapentin2512 – 34
Placebo2515 – 34
Post-taper
GroupValue95% CI
Gabapentin267 – 33
Placebo259 – 35
Olfactory Dysfunction Outcomes Rating (ODOR) Secondary · 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
GroupValue95% CI
Gabapentin2310 – 31
Placebo54.530 – 96
Fixed Dose
GroupValue95% CI
Gabapentin25.515 – 34
Placebo49.98 – 96
Post Taper
GroupValue95% CI
Gabapentin259 – 35
Placebo458 – 85
NASAL-7 Secondary · 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 d

Baseline
GroupValue95% CI
Gabapentin6
Placebo10
Gabapentin8
Placebo12
Gabapentin2
Placebo3
Gabapentin2
Placebo1
Fixed Dose
GroupValue95% CI
Gabapentin4
Placebo7
Gabapentin5
Placebo9
Gabapentin4
Placebo6
Gabapentin5
Placebo4
Post taper
GroupValue95% CI
Gabapentin5
Placebo7
Gabapentin6
Placebo6
Gabapentin2
Placebo5
Gabapentin3
Placebo7
CGI-Severity of Smell Secondary · 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

Assessments of the Secondary Outcome Measures of Study Groups: Baseline
GroupValue95% CI
Gabapentin4
Placebo4
Gabapentin12
Placebo16
Gabapentin1
Placebo4
Gabapentin1
Placebo1
Fixed Dose
GroupValue95% CI
Gabapentin3
Placebo5
Gabapentin4
Placebo13
Gabapentin8
Placebo4
Gabapentin3
Placebo3
Post taper
GroupValue95% CI
Gabapentin2
Placebo3
Gabapentin7
Placebo13
Gabapentin5
Placebo6
Gabapentin2
Placebo2
CGI-S of Parosmia Secondary · 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.

Assessments of Secondary Outcome Measures of Study Groups: Baseline
GroupValue95% CI
Gabapentin7
Placebo6
Gabapentin9
Placebo8
Gabapentin2
Placebo7
Gabapentin0
Placebo4
Fixed Dose
GroupValue95% CI
Gabapentin2
Placebo3
Gabapentin6
Placebo6
Gabapentin4
Placebo9
Gabapentin5
Placebo7
Post tapper
GroupValue95% CI
Gabapentin2
Placebo2
Gabapentin5
Placebo9
Gabapentin6
Placebo9
Gabapentin2
Placebo4

Adverse events — posted to ClinicalTrials.gov

Time frame: If tolerated, all participants will complete the Titration period (≤ 4 weeks), Fixed-Dose period (8 weeks), and Taper-Down period (2 weeks) for maximum 14 weeks of active participation. In addition, there will be a 4-week, post-Taper completion follow-up for maximum total of 18-week trial duration. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Gabapentin
Serious: 0/18 (0%)
Deaths: 0/18
Placebo
Serious: 0/26 (0%)
Deaths: 0/26
Other adverse events (4 terms — click to expand)

ReactionSystemGabapentinPlacebo
fatigueInvestigations
dizzinessInvestigations
brain fogInvestigations
weight gainInvestigations

Data from ClinicalTrials.gov NCT05184192 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Clinical trials on the pharmacological treatment of long COVID: A systematic review.
    Chee YJ, Fan BE, Young BE, Dalan R, et al · · 2023 · cited 55× · PMID 36349400 · DOI 10.1002/jmv.28289
  2. Post-COVID-19 Anosmia and Therapies: Stay Tuned for New Drugs to Sniff Out.
    Riccardi G, Niccolini GF, Bellizzi MG, Fiore M, et al · · 2023 · cited 11× · PMID 37366867 · DOI 10.3390/diseases11020079
  3. Efficacy of Gabapentin For Post-COVID-19 Olfactory Dysfunction: The GRACE Randomized Clinical Trial.
    Mahadev A, Hentati F, Miller B, Bao J, et al · · 2023 · cited 7× · PMID 37733356 · DOI 10.1001/jamaoto.2023.2958

Verify or expand the search:

Other recruiting trials for COVID-19

Currently open trials in the same condition.

Other Washington University School of Medicine trials

Trials by the same sponsor.

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