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Fluvoxamine to Augment Olfactory Recovery For Long COVID-19 Parosmia (FluCOP)

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: NCT05216614
Recruitment Status : Withdrawn (Unable to obtain investigational product)
First Posted : January 31, 2022
Last Update Posted : March 11, 2022
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Study Description
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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.

Condition or disease Intervention/treatment Phase
COVID-19 Olfactory Disorder Parosmia Drug: Fluvoxamine Drug: Placebo Phase 2

Detailed Description:
The drug will be given over a 14 weeks with six weeks titrating up, six weeks maintaining highest dose, and up to two weeks tapering down. Assessments will be collected following week 12 to measure change in olfactory function from baseline between the two study groups.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 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: Fluvoxamine to Augment Olfactory Recovery For Long COVID-19 Parosmia (FluCOP Trial)
Actual Study Start Date : December 14, 2021
Actual Primary Completion Date : February 22, 2022
Actual Study Completion Date : February 22, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Fluvoxamine

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
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.
Other Name: Luvox
Placebo Comparator: Placebo

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


Outcome Measures
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Primary Outcome Measures :
  1. Clinical Global Impression Scale (CGI) [ Time Frame: 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 ]

    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.



Secondary Outcome Measures :
  1. University of Pennsylvania Smell Identification Test (UPSIT) [ Time Frame: Baseline and Week 12 after completion of fixed-dose period, prior to taper down, to measure change from baseline ]
    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 and Week 12 after completion of fixed-dose period, prior to taper down, to measure change from baseline ]
    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. The Depression, Anxiety and Stress Scale - 21 Items (DASS-21) [ Time Frame: Baseline and Week 12 after completion of fixed-dose period, prior to taper down, to measure change from baseline ]
    The DASS-21 is a set of three self-report scales designed to measure the emotional state of depression, anxiety, and stress. Each of the three DASS-21 scales contains 7 items, divided into subscales with similar content. The depression scale assesses dysphoria, hopelessness, devaluation of life, self-deprecation, lack of interest / involvement, anhedonia and inertia. The anxiety scale assesses autonomic arousal, skeletal muscle effects, situational anxiety, and subjective experience of anxious affect. The stress scale is sensitive to levels of chronic non- specific arousal and assesses difficulty relaxing, nervous arousal, and being easily upset / agitated, irritable / over-reactive and impatient. Scores for depression, anxiety and stress are calculated by summing the scores for the relevant items.

  4. The Smell Catastrophizing Scale (SCS) [ Time Frame: Baseline and Week 12 after completion of fixed-dose period, prior to taper down, to measure change from baseline ]
    The SCS is a 13-item scale that asks the participants to describe the degree to which they have specific thoughts and feelings as a result of their sense of smell problems.

  5. 36-Item Short Form Health Survey (SF-36) [ Time Frame: Baseline and Week 12 after completion of fixed-dose period, prior to taper down, to measure change from baseline ]
    The SF-36 is a 36-item questionnaire evaluating physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. This test allows us to study the general health overall quality of life changes for those suffering from COVID-19 related OD.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
Contacts and Locations
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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): NCT05216614


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
More Information
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Additional Information:

Publications:
Jiang X, Finucane HK, Schumacher FR, Schmit SL, Tyrer JP, Han Y, Michailidou K, Lesseur C, Kuchenbaecker KB, Dennis J, Conti DV, Casey G, Gaudet MM, Huyghe JR, Albanes D, Aldrich MC, Andrew AS, Andrulis IL, Anton-Culver H, Antoniou AC, Antonenkova NN, Arnold SM, Aronson KJ, Arun BK, Bandera EV, Barkardottir RB, Barnes DR, Batra J, Beckmann MW, Benitez J, Benlloch S, Berchuck A, Berndt SI, Bickeboller H, Bien SA, Blomqvist C, Boccia S, Bogdanova NV, Bojesen SE, Bolla MK, Brauch H, Brenner H, Brenton JD, Brook MN, Brunet J, Brunnstrom H, Buchanan DD, Burwinkel B, Butzow R, Cadoni G, Caldes T, Caligo MA, Campbell I, Campbell PT, Cancel-Tassin G, Cannon-Albright L, Campa D, Caporaso N, Carvalho AL, Chan AT, Chang-Claude J, Chanock SJ, Chen C, Christiani DC, Claes KBM, Claessens F, Clements J, Collee JM, Correa MC, Couch FJ, Cox A, Cunningham JM, Cybulski C, Czene K, Daly MB, deFazio A, Devilee P, Diez O, Gago-Dominguez M, Donovan JL, Dork T, Duell EJ, Dunning AM, Dwek M, Eccles DM, Edlund CK, Edwards DRV, Ellberg C, Evans DG, Fasching PA, Ferris RL, Liloglou T, Figueiredo JC, Fletcher O, Fortner RT, Fostira F, Franceschi S, Friedman E, Gallinger SJ, Ganz PA, Garber J, Garcia-Saenz JA, Gayther SA, Giles GG, Godwin AK, Goldberg MS, Goldgar DE, Goode EL, Goodman MT, Goodman G, Grankvist K, Greene MH, Gronberg H, Gronwald J, Guenel P, Hakansson N, Hall P, Hamann U, Hamdy FC, Hamilton RJ, Hampe J, Haugen A, Heitz F, Herrero R, Hillemanns P, Hoffmeister M, Hogdall E, Hong YC, Hopper JL, Houlston R, Hulick PJ, Hunter DJ, Huntsman DG, Idos G, Imyanitov EN, Ingles SA, Isaacs C, Jakubowska A, James P, Jenkins MA, Johansson M, Johansson M, John EM, Joshi AD, Kaneva R, Karlan BY, Kelemen LE, Kuhl T, Khaw KT, Khusnutdinova E, Kibel AS, Kiemeney LA, Kim J, Kjaer SK, Knight JA, Kogevinas M, Kote-Jarai Z, Koutros S, Kristensen VN, Kupryjanczyk J, Lacko M, Lam S, Lambrechts D, Landi MT, Lazarus P, Le ND, Lee E, Lejbkowicz F, Lenz HJ, Leslie G, Lessel D, Lester J, Levine DA, Li L, Li CI, Lindblom A, Lindor NM, Liu G, Loupakis F, Lubinski J, Maehle L, Maier C, Mannermaa A, Marchand LL, Margolin S, May T, McGuffog L, Meindl A, Middha P, Miller A, Milne RL, MacInnis RJ, Modugno F, Montagna M, Moreno V, Moysich KB, Mucci L, Muir K, Mulligan AM, Nathanson KL, Neal DE, Ness AR, Neuhausen SL, Nevanlinna H, Newcomb PA, Newcomb LF, Nielsen FC, Nikitina-Zake L, Nordestgaard BG, Nussbaum RL, Offit K, Olah E, Olama AAA, Olopade OI, Olshan AF, Olsson H, Osorio A, Pandha H, Park JY, Pashayan N, Parsons MT, Pejovic T, Penney KL, Peters WHM, Phelan CM, Phipps AI, Plaseska-Karanfilska D, Pring M, Prokofyeva D, Radice P, Stefansson K, Ramus SJ, Raskin L, Rennert G, Rennert HS, van Rensburg EJ, Riggan MJ, Risch HA, Risch A, Roobol MJ, Rosenstein BS, Rossing MA, De Ruyck K, Saloustros E, Sandler DP, Sawyer EJ, Schabath MB, Schleutker J, Schmidt MK, Setiawan VW, Shen H, Siegel EM, Sieh W, Singer CF, Slattery ML, Sorensen KD, Southey MC, Spurdle AB, Stanford JL, Stevens VL, Stintzing S, Stone J, Sundfeldt K, Sutphen R, Swerdlow AJ, Tajara EH, Tangen CM, Tardon A, Taylor JA, Teare MD, Teixeira MR, Terry MB, Terry KL, Thibodeau SN, Thomassen M, Bjorge L, Tischkowitz M, Toland AE, Torres D, Townsend PA, Travis RC, Tung N, Tworoger SS, Ulrich CM, Usmani N, Vachon CM, Van Nieuwenhuysen E, Vega A, Aguado-Barrera ME, Wang Q, Webb PM, Weinberg CR, Weinstein S, Weissler MC, Weitzel JN, West CML, White E, Whittemore AS, Wichmann HE, Wiklund F, Winqvist R, Wolk A, Woll P, Woods M, Wu AH, Wu X, Yannoukakos D, Zheng W, Zienolddiny S, Ziogas A, Zorn KK, Lane JM, Saxena R, Thomas D, Hung RJ, Diergaarde B, McKay J, Peters U, Hsu L, Garcia-Closas M, Eeles RA, Chenevix-Trench G, Brennan PJ, Haiman CA, Simard J, Easton DF, Gruber SB, Pharoah PDP, Price AL, Pasaniuc B, Amos CI, Kraft P, Lindstrom S. Shared heritability and functional enrichment across six solid cancers. Nat Commun. 2019 Jan 25;10(1):431. doi: 10.1038/s41467-018-08054-4. Erratum In: Nat Commun. 2019 Sep 23;10(1):4386.

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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT05216614    
Other Study ID Numbers: 202111124
First Posted: January 31, 2022    Key Record Dates
Last Update Posted: March 11, 2022
Last Verified: February 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
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
Fluvoxamine
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents