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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05184192
Recruitment Status : Enrolling by invitation
First Posted : January 11, 2022
Last Update Posted : June 21, 2022
Sponsor:
Information provided by (Responsible Party):
Jay F. Piccirillo, MD, Washington University School of Medicine

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.

Condition or disease Intervention/treatment Phase
COVID-19 Olfactory Disorder Anosmia Hyposmia Parosmia Drug: Gabapentin gelatin capsules 300mg Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blinded, randomized, placebo-controlled trial
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: 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
Primary Purpose: Treatment
Official Title: Efficacy of Gabapentin for Post-Covid-19 Olfactory Dysfunction
Actual Study Start Date : January 10, 2022
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine


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 Name: 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




Primary Outcome Measures :
  1. Clinical Global Impression of Improvement Scale (CGI-I) [ Time Frame: After completion of eight-week fixed-dose period ]

    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



Secondary Outcome Measures :
  1. 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 ]
    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.

  2. 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 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

  3. 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, 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).

  4. Clinical Global Impression - Severity Scale for Parosmics (CGI-P) [ Time Frame: Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period ]
    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.

  5. Clinical Global Impression of Severity Scale (CGI-S) [ Time Frame: Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down period ]
    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.

  6. Clinical Global Impression of Improvement Scale (CGI-I) [ Time Frame: 4 weeks after completion of Taper-Down Period. ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05184192


Locations
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United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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Principal Investigator: Jay F Piccirillo, MD Washington University School of Medicine
Additional Information:
Publications:

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Responsible Party: Jay F. Piccirillo, MD, Principal Investigator, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT05184192    
Other Study ID Numbers: 202110011
First Posted: January 11, 2022    Key Record Dates
Last Update Posted: June 21, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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COVID-19
Anosmia
Olfaction Disorders
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Gabapentin
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anticonvulsants
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents