Efficacy of Gabapentin for Post-Covid-19 Olfactory Dysfunction

NCT ID: NCT05184192

Last Updated: 2025-03-04

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

68 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-01-10

Study Completion Date

2023-08-29

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.

Conditions

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COVID-19 Olfactory Disorder Anosmia Hyposmia Parosmia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Double-blinded, randomized, placebo-controlled trial
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
double-blinded, both participants and investigators will be blinded. Intervention will be packaged in blinded fashion by pharmacist before being shipped to participants by research assistant

Study Groups

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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.

Group Type EXPERIMENTAL

Gabapentin gelatin capsules 300mg

Intervention Type DRUG

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.

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

lactose monohydrate NF

Interventions

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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.

Intervention Type DRUG

Placebo

lactose monohydrate NF

Intervention Type DRUG

Other Intervention Names

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Letco

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jay F Piccirillo, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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Washington University

St Louis, Missouri, United States

Site Status

Countries

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United States

References

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Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, Dequanter D, Blecic S, El Afia F, Distinguin L, Chekkoury-Idrissi Y, Hans S, Delgado IL, Calvo-Henriquez C, Lavigne P, Falanga C, Barillari MR, Cammaroto G, Khalife M, Leich P, Souchay C, Rossi C, Journe F, Hsieh J, Edjlali M, Carlier R, Ris L, Lovato A, De Filippis C, Coppee F, Fakhry N, Ayad T, Saussez S. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020 Aug;277(8):2251-2261. doi: 10.1007/s00405-020-05965-1. Epub 2020 Apr 6.

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Damm M, Pikart LK, Reimann H, Burkert S, Goktas O, Haxel B, Frey S, Charalampakis I, Beule A, Renner B, Hummel T, Huttenbrink KB. Olfactory training is helpful in postinfectious olfactory loss: a randomized, controlled, multicenter study. Laryngoscope. 2014 Apr;124(4):826-31. doi: 10.1002/lary.24340. Epub 2013 Sep 19.

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Schopf CL, Ablinger C, Geisler SM, Stanika RI, Campiglio M, Kaufmann WA, Nimmervoll B, Schlick B, Brockhaus J, Missler M, Shigemoto R, Obermair GJ. Presynaptic alpha2delta subunits are key organizers of glutamatergic synapses. Proc Natl Acad Sci U S A. 2021 Apr 6;118(14):e1920827118. doi: 10.1073/pnas.1920827118.

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Lopez-D'alessandro E, Escovich L. Combination of alpha lipoic acid and gabapentin, its efficacy in the treatment of Burning Mouth Syndrome: a randomized, double-blind, placebo controlled trial. Med Oral Patol Oral Cir Bucal. 2011 Aug 1;16(5):e635-40. doi: 10.4317/medoral.16942.

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Doty RL, Shaman P, Kimmelman CP, Dann MS. University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic. Laryngoscope. 1984 Feb;94(2 Pt 1):176-8. doi: 10.1288/00005537-198402000-00004.

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Mahadev A, Hentati F, Miller B, Bao J, Perrin A, Kallogjeri D, Piccirillo JF. Efficacy of Gabapentin For Post-COVID-19 Olfactory Dysfunction: The GRACE Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2023 Dec 1;149(12):1111-1119. doi: 10.1001/jamaoto.2023.2958.

Reference Type DERIVED
PMID: 37733356 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://covid19.who.int/

World Health Organization Covid-19 Dashboard

Other Identifiers

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202110011

Identifier Type: -

Identifier Source: org_study_id

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