Efficacy of Gabapentin for Post-Covid-19 Olfactory Dysfunction

COVID-19 Clinical Trial

— GRACE  

Official title:

Efficacy of Gabapentin for Post-Covid-19 Olfactory Dysfunction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05184192
• Other study ID #: 202110011
• Status: Completed
• Phase: Phase 2
• Start date: January 10, 2022
• Est. completion date: August 29, 2023

Study information

• Verified date: April 2024
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: August 29, 2023
• Est. primary completion date: August 29, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anosmia
• COVID-19
• Hyposmia
• Olfaction Disorders
• Olfactory Disorder

Intervention

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.
• Placebo
lactose monohydrate NF

Locations

Country	Name	City	State
United States	Washington University	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (15)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Global Impression of Improvement Scale (CGI-I)	The CGI-Severity scale ranges from 1 to 7, where 1 is Very Much Improved and 7 is Very Much Worsened. This assessment will provide subjective data on patients' change in olfaction from baseline.; Participants reporting 3 as Minimally Improved, 2 as Much Improved, or 1 as Very Much Improved in the CGI-I will be deemed responders to treatment, and the number of responders to non-responders will be compared between the two arms	After completion of eight-week fixed-dose period
Secondary	University of Pennsylvania Smell Identification Test (UPSIT)	The UPSIT is composed of 40 strips of microencapsulated odorants, which are present on the bottom of each page, just below a four-alternative multiple-choice question. For a given item, the patient releases an odor by scratching the microencapsulated pad with a pencil tip, smells the pad, and indicates the odor quality from four alternatives. Even if no smell is perceived, a response is required (i.e., the test is forced-choice). The subject's total correct score out of the 40 items is determined and provides an objective measure of olfactory function.	Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period
Secondary	Olfactory Dysfunction Outcomes Rating (ODOR)	The ODOR questionnaire is a 28-item disease-specific health status survey to assess the physical problems, functional impairments, and emotional consequences secondary to olfactory dysfunction. ODOR was developed and validated by Dr. Jake Lee and colleagues in the Clinical Outcomes Research Office at Washington University	Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period
Secondary	NASAL-7	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, 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
Secondary	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.	Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period
Secondary	Clinical Global Impression of Severity Scale (CGI-S)	The CGI-S Scale is a subjective rating of severity which ranges from 1 - 7 (1 is normal function and 7 is complete anosmia) to measure severity of smell loss.	Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period
Secondary	Clinical Global Impression of Improvement Scale (CGI-I)	The CGI-Severity scale ranges from 1 to 7, where 1 is Very Much Improved and 7 is Very Much Worsened. This assessment will provide subjective data on patients' change in olfaction from baseline.	4 weeks after completion of Taper-Down Period.

External Links

•   CDC Covid-19 data tracker
•   World Health Organization Covid-19 Dashboard