Fluvoxamine to Augment Olfactory Recovery For Long COVID-19 Parosmia

NCT05216614 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 202111124
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the efficacy of oral fluvoxamine in olfactory improvement following Covid-19- associated parosmia. This is a randomized, double-blinded, placebo-controlled trial.

Conditions

COVID-19; Olfactory Disorder; Parosmia

Outcome Measures

Primary Outcomes (1)

• Clinical Global Impression Scale (CGI)

  The CGI has two components - the CGI-Severity and the CGI-Improvement. Scores on the CGI-Severity Scale range from 1 to 7 (1 is Normal, 7 is Complete loss of smell) and provide information on the patient's perceived severity of their dysfunction at baseline. The score on the CGI-Improvement Scale ranges from 1 to 7 (1 is Very Much Improved, 7 is Very Much Worsened). Each rating is well defined to maximize accuracy. 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. The Clinical Global Impression-Severity Scale for Parosmia (CGI-P) will also be used. The CGI-P Scale ranges from 1 to 5, where 1 is No Distortion, 2 is Mild Distortion, 3 is Moderate Distortion, 4 is Mostly Distorted, and 5 is Complete Distortion.

  CGI-S and CGI-P will be administered at Baseline and Week 12 after completion of fixed-dose period, prior to taper down, to measure change. CGI-I will be administered at Week 12 after completion of fixed-dose period, prior to taper down

Secondary Outcomes (5)

• University of Pennsylvania Smell Identification Test (UPSIT)

  Baseline and Week 12 after completion of fixed-dose period, prior to taper down, to measure change from baseline

• Olfactory Dysfunction Outcomes Rating (ODOR)

  Baseline and Week 12 after completion of fixed-dose period, prior to taper down, to measure change from baseline

• The Depression, Anxiety and Stress Scale - 21 Items (DASS-21)

  Baseline and Week 12 after completion of fixed-dose period, prior to taper down, to measure change from baseline

• The Smell Catastrophizing Scale (SCS)

  Baseline and Week 12 after completion of fixed-dose period, prior to taper down, to measure change from baseline

• 36-Item Short Form Health Survey (SF-36)

  Baseline and Week 12 after completion of fixed-dose period, prior to taper down, to measure change from baseline

Study Arms (2)

Fluvoxamine

EXPERIMENTAL

This arm will be given the active treatment, oral fluvoxamine capsules of 25 mg each. The first six weeks will be gradual titration (weeks 1 \& 2 25mg BID, weeks 3 \& 4 75mg BID, weeks 5 \& 6 100mg BID). The following six weeks will be fixed dose of 100mg TID. The last two weeks will be a taper down (first week 50mg BID and second week 25mg BID) There will be 14 weeks of active treatment and assessments will be conducted after completion of week 12, prior to beginning taper down period.

Drug: Fluvoxamine

Placebo

PLACEBO COMPARATOR

Placebo capsules that look, smell, and taste like fluvoxamine capsules will be given to the placebo arm. To preserve double-blinding of the study, subjects will receive one capsule BID during the first six weeks following the titration schedule and one capsule TID during the next six weeks for the fixed-dose period. Subjects will then taper-down placebo to imitate the fluvoxamine arm for two weeks. Assessments will be conducted at 12 weeks following completion of fixed-dose period, prior to starting taper down period.

Drug: Placebo

Interventions

Fluvoxamine DRUG

Fluvoxamine is an SSRI used for depression and anxiety disorders. This study will investigate the efficacy of fluvoxamine for improvement of olfactory dysfunction in subjects with post-Covid-19 parosmia.

Also known as: Luvox

Fluvoxamine

Placebo DRUG

lactose placebo capsules identical to fluvoxamine capsules in order to preserve blind

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women between the ages 18 to 70 years
• Residing within the states of Missouri or Illinois
• Complaints of odors of certain things or everything are distorted
• Olfactory dysfunction that has persisted for \>2 months after suspected COVID-19 infection
• Ability to read, write, and understand English

You may not qualify if:

• History of olfactory dysfunction prior to COVID-19 infection
• Any use of concomitant therapies specifically for the treatment of olfactory dysfunction
• History of olfactory dysfunction of longer than 12 months
• History of bipolar disorder as SSRIs can theoretically destabilize bipolar disorder
• Participants with symptoms of depression as evidenced by a score of 10 or greater on the Patient Health Questionnaire-9 (PHQ-9).95 The PHQ-9 is a nine-item questionnaire designed to assess and aid in diagnosing patients with depression in clinical and community settings.
• History of neurodegenerative disease (i.e., Alzheimer's dementia, Parkinson's disease, Lewy body dementia, frontotemporal dementia)
• History of chronic rhinosinusitis or sinus surgery
• Pregnant or breastfeeding mothers.
• Already enrolled in another COVID 19 medication trial or receipt of monoclonal antibody infusion.
• Taking donepezil or fluoxetine (rationale: these drugs are S1R agonists) or sertraline (a S1R antagonist).
• Participants taking theophylline, tizanidine, clozapine, or olanzapine (drugs with a narrow therapeutic index that are primarily metabolized by CYP 1A2, which is inhibited by fluvoxamine.
• Taking another SSRI, unless at a low dose (e.g., escitalopram 5mg) such that adding fluvoxamine would not put patient at risk for serotonin syndrome.
• Taking coumadin based on theoretical risk of increased bleeding with fluvoxamine.
• Unable to provide informed consent.
• Unable to perform the study procedures.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

Location

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Related Links

• article discussing early symptoms of Covid-19 infection
• American Academy of Otolaryngology - Head and Neck Surgery
• ENT UK site discussing loss of smell as a covid-19 early symptom
• article discussing the Depression Anxiety \& Stress Scale published by University of Wisconsin - Madison
• article discussing the ECDEU Assessment Manual published in national catalogue

MeSH Terms

Conditions

COVID-19; Olfaction Disorders

Interventions

Fluvoxamine

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

Intervention Hierarchy (Ancestors)

Oximes; Hydroxylamines; Amines; Organic Chemicals

Study Officials

• Jay F Piccirillo, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

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 24, 2022
• First Posted: January 31, 2022
• Study Start: December 14, 2021
• Primary Completion: February 22, 2022
• Study Completion: February 22, 2022
• Last Updated: March 11, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)