Efficacy of Gabapentin for Post-Covid-19 Olfactory Dysfunction

NCT05184192 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 202110011
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19; Olfactory Disorder; Anosmia; Hyposmia; Parosmia

Outcome Measures

Primary Outcomes (1)

• Clinical Global Impression of Improvement Scale (CGI-I)

  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 Outcomes (5)

• 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

• Olfactory Dysfunction Outcomes Rating (ODOR)

  Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period

• NASAL-7

  Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period

• CGI-Severity of Smell

  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

Study Arms (2)

Gabapentin

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Gabapentin gelatin capsules 300mg 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.

Also known as: Letco

Gabapentin

Placebo DRUG

lactose monohydrate NF

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

Location

Related Publications (16)

• 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.

  PMID: 32253535 BACKGROUND

• Boscolo-Rizzo P, Borsetto D, Fabbris C, Spinato G, Frezza D, Menegaldo A, Mularoni F, Gaudioso P, Cazzador D, Marciani S, Frasconi S, Ferraro M, Berro C, Varago C, Nicolai P, Tirelli G, Da Mosto MC, Obholzer R, Rigoli R, Polesel J, Hopkins C. Evolution of Altered Sense of Smell or Taste in Patients With Mildly Symptomatic COVID-19. JAMA Otolaryngol Head Neck Surg. 2020 Aug 1;146(8):729-732. doi: 10.1001/jamaoto.2020.1379.

  PMID: 32614442 BACKGROUND

• Hummel T, Rissom K, Reden J, Hahner A, Weidenbecher M, Huttenbrink KB. Effects of olfactory training in patients with olfactory loss. Laryngoscope. 2009 Mar;119(3):496-9. doi: 10.1002/lary.20101.

  PMID: 19235739 BACKGROUND

• Turner JH. Olfactory training: what is the evidence? Int Forum Allergy Rhinol. 2020 Nov;10(11):1199-1200. doi: 10.1002/alr.22681. Epub 2020 Sep 3. No abstract available.

  PMID: 32776673 BACKGROUND

• Biole C, Bianco M, Nunez-Gil IJ, Cerrato E, Spirito A, Roubin SR, Viana-Llamas MC, Gonzalez A, Castro-Mejia AF, Eid CM, Fernandez-Perez C, Uribarri A, Alfonso-Rodriguez E, Ugo F, Guerra F, Feltes G, Akin I, Fernandez-Rozas I, Blasco-Angulo N, Huang J, Aguado MG, Pepe M, Romero R, Becerra-Munoz VM, Estrada V, Macaya C. Gender Differences in the Presentation and Outcomes of Hospitalized Patients With COVID-19. J Hosp Med. 2021 Jun;16(6):349-352. doi: 10.12788/jhm.3594.

  PMID: 34129486 BACKGROUND

• Butowt R, von Bartheld CS. Anosmia in COVID-19: Underlying Mechanisms and Assessment of an Olfactory Route to Brain Infection. Neuroscientist. 2021 Dec;27(6):582-603. doi: 10.1177/1073858420956905. Epub 2020 Sep 11.

  PMID: 32914699 BACKGROUND

• Bilinska K, Butowt R. Anosmia in COVID-19: A Bumpy Road to Establishing a Cellular Mechanism. ACS Chem Neurosci. 2020 Aug 5;11(15):2152-2155. doi: 10.1021/acschemneuro.0c00406. Epub 2020 Jul 16.

  PMID: 32673476 BACKGROUND

• Kuba K, Imai Y, Penninger JM. Multiple functions of angiotensin-converting enzyme 2 and its relevance in cardiovascular diseases. Circ J. 2013;77(2):301-8. doi: 10.1253/circj.cj-12-1544. Epub 2013 Jan 18.

  PMID: 23328447 BACKGROUND

• Mollica V, Rizzo A, Massari F. The pivotal role of TMPRSS2 in coronavirus disease 2019 and prostate cancer. Future Oncol. 2020 Sep;16(27):2029-2033. doi: 10.2217/fon-2020-0571. Epub 2020 Jul 13. No abstract available.

  PMID: 32658591 BACKGROUND

• 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.

  PMID: 23929687 BACKGROUND

• 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.

  PMID: 33782113 BACKGROUND

• 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.

  PMID: 20711135 BACKGROUND

• 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.

  PMID: 6694486 BACKGROUND

• Doty RL. Olfactory dysfunction and its measurement in the clinic. World J Otorhinolaryngol Head Neck Surg. 2015 Oct 26;1(1):28-33. doi: 10.1016/j.wjorl.2015.09.007. eCollection 2015 Sep.

  PMID: 29204537 BACKGROUND

• Mersfelder TL, Nichols WH. Gabapentin: Abuse, Dependence, and Withdrawal. Ann Pharmacother. 2016 Mar;50(3):229-33. doi: 10.1177/1060028015620800. Epub 2015 Dec 31.

  PMID: 26721643 BACKGROUND

• 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.

  PMID: 37733356 DERIVED

Related Links

• World Health Organization Covid-19 Dashboard

MeSH Terms

Conditions

COVID-19; Anosmia; Olfaction Disorders

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Jay F. Piccirillo
• Organization: Washington University, Department of Otolaryngology - Head and Neck Surgery

piccirj@wustl.edu

314-362-8641

Study Officials

• Jay F Piccirillo, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blinded, randomized, placebo-controlled trial

Study Record Dates

• First Submitted: January 6, 2022
• First Posted: January 11, 2022
• Study Start: January 10, 2022
• Primary Completion: August 29, 2023
• Study Completion: August 29, 2023
• Last Updated: March 4, 2025
• Results First Posted: March 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)