Fluvoxamine to Augment Olfactory Recovery For Long COVID-19 Parosmia

COVID-19 Clinical Trial

— FluCOP  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05216614
• Other study ID #: 202111124
• Status: Withdrawn
• Phase: Phase 2
• Start date: December 14, 2021
• Est. completion date: February 22, 2022

Study information

• Verified date: February 2022
• 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 fluvoxamine in olfactory improvement following Covid-19- associated parosmia. This is a randomized, double-blinded, placebo-controlled trial.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 22, 2022
• Est. primary completion date: February 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Olfaction Disorders
• Olfactory Disorder

Intervention

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.
• Placebo
lactose placebo capsules identical to fluvoxamine capsules in order to preserve blind

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, 

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* Note: There are 100 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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 and Week 12 after completion of fixed-dose period, prior to taper down, to measure change from baseline
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 and Week 12 after completion of fixed-dose period, prior to taper down, to measure change from baseline
Secondary	The Depression, Anxiety and Stress Scale - 21 Items (DASS-21)	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.	Baseline and Week 12 after completion of fixed-dose period, prior to taper down, to measure change from baseline
Secondary	The Smell Catastrophizing Scale (SCS)	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.	Baseline and Week 12 after completion of fixed-dose period, prior to taper down, to measure change from baseline
Secondary	36-Item Short Form Health Survey (SF-36)	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.	Baseline and Week 12 after completion of fixed-dose period, prior to taper down, to measure change from baseline

External Links

•   American Academy of Otolaryngology - Head and Neck Surgery
•   article discussing early symptoms of Covid-19 infection
•   article discussing the Depression Anxiety & Stress Scale published by University of Wisconsin - Madison
•   article published in New York Times discussing survivors of Covid now haunted by symptoms
•   ENT UK site discussing loss of smell as a covid-19 early symptom