Fluoxetine to Reduce Hospitalization From COVID-19 Infection (FloR COVID-19)

NCT04570449 | Withdrawn Early Phase 1 FDA Drug

• 1 other identifier: 00015598
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The current research is a pilot study to determine the feasibility of recruiting and retaining 40 participants diagnosed with COVID-19. The purpose is to observe the early use of fluoxetine (commonly known as Prozac) to reduce the severity of the COVID-19 illness. Fluoxetine is a drug that has been approved by the U.S. Food and Drug Administration (FDA) since 1987 for various mental health disorders.

Conditions

Covid19

Keywords

covid-19; fluoxetine; cytokine; anti-inflammatory; IL-6

Outcome Measures

Primary Outcomes (2)

• Rate of hospitalization

  Measures number of subjects hospitalized for COVID-19 symptoms

  8 weeks

• Physical symptoms assessed through daily checklist

  The 23-item daily symptom checklist measures the presence or absence of COVID-related symptoms (e.g. shortness of breath, fever, chills) and other possible symptoms (e.g. ear pain, vomit, seizures).

  8 weeks

Secondary Outcomes (6)

• Rate of intubation

  8 weeks

• Rate of death

  8 weeks

• Depressive symptoms assessed weekly

  8 weeks

• Post traumatic stress disorder symptoms assessed weekly

  8 weeks

• Anxiety symptoms assessed weekly

  8 weeks

Study Arms (2)

Fluoxetine

EXPERIMENTAL

Participants instructed to take fluoxetine 20 mg capsule orally daily for 8 weeks in the following schedule: Week 1 = 1 pill (20 mg), Week 2 = 2 pills (40 mg), Weeks 3-6 = 3 pills (60 mg), Week 7 = 2 pills (40 mg), Week 8 = pill (20 mg)

Drug: Fluoxetine

Placebo

PLACEBO COMPARATOR

Participants instructed to take fluoxetine placebo capsule matching fluoxetine orally daily for 8 weeks in the following schedule: Week 1 = 1 pill, Week 2 = 2 pills, Weeks 3-6 = 3 pills, Week 7 = 2 pills, Week 8 = pill

Drug: Placebo

Interventions

Fluoxetine DRUG

20 mg capsule

Fluoxetine

Placebo DRUG

fluoxetine placebo capsule

Placebo

Eligibility Criteria

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

You may qualify if:

• English speaking participant
• years of age or older
• able to give informed consent
• Tested positive for active SARS-CoV-2 infection and
• It's been less than 10 days since symptoms first appeared;
• Fever persists for longer than 24 hours without the use of fever reducing medications; and
• Experiencing other symptoms of COVID-19 as described by the CDC

You may not qualify if:

• Prisoner or institutionalized patient
• Unable to give informed consent
• Less than 18 years of age
• Hospitalization
• Active bleeding requiring blood products in past week
• Diagnosed with bipolar disorder and not on mood stabilizing medication
• Known allergy or hypersensitivity to fluoxetine
• Currently taking a monoamine oxidase inhibitor (MAOI)
• Currently taking an selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI)
• Outpatient and currently taking hydroxychloroquine
• Known pregnancy
• Breastfeeding
• Known prolonged QTc, such as congenital prolonged QTc syndromes

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

Milton S. Hershey Medical Center Clinical Research Center

Hershey, Pennsylvania, 17033, United States

Location

Related Publications (21)

• Amitai M, Taler M, Carmel M, Michaelovsky E, Eilat T, Yablonski M, Orpaz N, Chen A, Apter A, Weizman A, Fennig S. The Relationship Between Plasma Cytokine Levels and Response to Selective Serotonin Reuptake Inhibitor Treatment in Children and Adolescents with Depression and/or Anxiety Disorders. J Child Adolesc Psychopharmacol. 2016 Oct;26(8):727-732. doi: 10.1089/cap.2015.0147. Epub 2016 Jan 15.

  PMID: 26771135 BACKGROUND

• Blatteau JE, Barre S, Pascual A, Castagna O, Abraini JH, Risso JJ, Vallee N. Protective effects of fluoxetine on decompression sickness in mice. PLoS One. 2012;7(11):e49069. doi: 10.1371/journal.pone.0049069. Epub 2012 Nov 8.

  PMID: 23145072 BACKGROUND

• Blatteau JE, de Maistre S, Lambrechts K, Abraini J, Risso JJ, Vallee N. Fluoxetine stimulates anti-inflammatory IL-10 cytokine production and attenuates sensory deficits in a rat model of decompression sickness. J Appl Physiol (1985). 2015 Dec 15;119(12):1393-9. doi: 10.1152/japplphysiol.00602.2015. Epub 2015 Oct 22.

  PMID: 26494447 BACKGROUND

• Branco-de-Almeida LS, Kajiya M, Cardoso CR, Silva MJ, Ohta K, Rosalen PL, Franco GC, Han X, Taubman MA, Kawai T. Selective serotonin reuptake inhibitors attenuate the antigen presentation from dendritic cells to effector T lymphocytes. FEMS Immunol Med Microbiol. 2011 Aug;62(3):283-94. doi: 10.1111/j.1574-695X.2011.00816.x. Epub 2011 Jun 16.

  PMID: 21569123 BACKGROUND

• Cai Z, Liu J, Bian H, Cai J, Jin Q, Han J. Fluoxetine, an Antidepressant Drug, Inhibited Cigarette Smoke-Induced Pulmonary Inflammation and Apoptosis in Rats. Inflammation. 2017 Aug;40(4):1375-1381. doi: 10.1007/s10753-017-0580-y.

  PMID: 28477248 BACKGROUND

• Dong C, Zhang JC, Yao W, Ren Q, Yang C, Ma M, Han M, Saito R, Hashimoto K. Effects of escitalopram, R-citalopram, and reboxetine on serum levels of tumor necrosis factor-alpha, interleukin-10, and depression-like behavior in mice after lipopolysaccharide administration. Pharmacol Biochem Behav. 2016 May;144:7-12. doi: 10.1016/j.pbb.2016.02.005. Epub 2016 Feb 15.

  PMID: 26892759 BACKGROUND

• Durairaj H, Steury MD, Parameswaran N. Paroxetine differentially modulates LPS-induced TNFalpha and IL-6 production in mouse macrophages. Int Immunopharmacol. 2015 Apr;25(2):485-92. doi: 10.1016/j.intimp.2015.02.029. Epub 2015 Mar 2.

  PMID: 25744603 BACKGROUND

• Gobin V, Van Steendam K, Denys D, Deforce D. Selective serotonin reuptake inhibitors as a novel class of immunosuppressants. Int Immunopharmacol. 2014 May;20(1):148-56. doi: 10.1016/j.intimp.2014.02.030. Epub 2014 Mar 6.

  PMID: 24613205 BACKGROUND

• Hashioka S, Klegeris A, Monji A, Kato T, Sawada M, McGeer PL, Kanba S. Antidepressants inhibit interferon-gamma-induced microglial production of IL-6 and nitric oxide. Exp Neurol. 2007 Jul;206(1):33-42. doi: 10.1016/j.expneurol.2007.03.022. Epub 2007 Mar 30.

  PMID: 17481608 BACKGROUND

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.

  PMID: 31986264 BACKGROUND

• Li XQ, Wang HM, Yang CG, Zhang XH, Han DD, Wang HL. Fluoxetine inhibited extracellular matrix of pulmonary artery and inflammation of lungs in monocrotaline-treated rats. Acta Pharmacol Sin. 2011 Feb;32(2):217-22. doi: 10.1038/aps.2010.187. Epub 2011 Jan 10.

  PMID: 21217769 BACKGROUND

• Liu D, Wang Z, Liu S, Wang F, Zhao S, Hao A. Anti-inflammatory effects of fluoxetine in lipopolysaccharide(LPS)-stimulated microglial cells. Neuropharmacology. 2011 Sep;61(4):592-9. doi: 10.1016/j.neuropharm.2011.04.033. Epub 2011 May 11.

  PMID: 21575647 BACKGROUND

• Liu RP, Zou M, Wang JY, Zhu JJ, Lai JM, Zhou LL, Chen SF, Zhang X, Zhu JH. Paroxetine ameliorates lipopolysaccharide-induced microglia activation via differential regulation of MAPK signaling. J Neuroinflammation. 2014 Mar 12;11:47. doi: 10.1186/1742-2094-11-47.

  PMID: 24618100 BACKGROUND

• Lu X, Wang J, Chen X, Jiang Y, Pan ZK. Rolipram Protects Mice from Gram-negative Bacterium Escherichia coli-induced Inflammation and Septic Shock. Sci Rep. 2020 Jan 13;10(1):175. doi: 10.1038/s41598-019-56899-6.

  PMID: 31932743 BACKGROUND

• Roumestan C, Michel A, Bichon F, Portet K, Detoc M, Henriquet C, Jaffuel D, Mathieu M. Anti-inflammatory properties of desipramine and fluoxetine. Respir Res. 2007 May 3;8(1):35. doi: 10.1186/1465-9921-8-35.

  PMID: 17477857 BACKGROUND

• Sherkawy MM, Abo-Youssef AM, Salama AAA, Ismaiel IE. Fluoxetine protects against OVA induced bronchial asthma and depression in rats. Eur J Pharmacol. 2018 Oct 15;837:25-32. doi: 10.1016/j.ejphar.2018.08.026. Epub 2018 Aug 23.

  PMID: 30145150 BACKGROUND

• Taraz M, Khatami MR, Dashti-Khavidaki S, Akhonzadeh S, Noorbala AA, Ghaeli P, Taraz S. Sertraline decreases serum level of interleukin-6 (IL-6) in hemodialysis patients with depression: results of a randomized double-blind, placebo-controlled clinical trial. Int Immunopharmacol. 2013 Nov;17(3):917-23. doi: 10.1016/j.intimp.2013.09.020. Epub 2013 Oct 11.

  PMID: 24121064 BACKGROUND

• Udina M, Hidalgo D, Navines R, Forns X, Sola R, Farre M, Capuron L, Vieta E, Martin-Santos R. Prophylactic antidepressant treatment of interferon-induced depression in chronic hepatitis C: a systematic review and meta-analysis. J Clin Psychiatry. 2014 Oct;75(10):e1113-21. doi: 10.4088/JCP.13r08800.

  PMID: 25373120 BACKGROUND

• Vollmar P, Haghikia A, Dermietzel R, Faustmann PM. Venlafaxine exhibits an anti-inflammatory effect in an inflammatory co-culture model. Int J Neuropsychopharmacol. 2008 Feb;11(1):111-7. doi: 10.1017/S1461145707007729. Epub 2007 Apr 20.

  PMID: 17445357 BACKGROUND

• Wang L, Wang R, Liu L, Qiao D, Baldwin DS, Hou R. Effects of SSRIs on peripheral inflammatory markers in patients with major depressive disorder: A systematic review and meta-analysis. Brain Behav Immun. 2019 Jul;79:24-38. doi: 10.1016/j.bbi.2019.02.021. Epub 2019 Feb 21.

  PMID: 30797959 BACKGROUND

• Young KC, Bai CH, Su HC, Tsai PJ, Pu CY, Liao CS, Lin YM, Lai HW, Chong LW, Tsai YS, Tsao CW. Fluoxetine a novel anti-hepatitis C virus agent via ROS-, JNK-, and PPARbeta/gamma-dependent pathways. Antiviral Res. 2014 Oct;110:158-67. doi: 10.1016/j.antiviral.2014.08.002. Epub 2014 Aug 21.

  PMID: 25151487 BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

Fluoxetine

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

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Study Officials

• Erika Saunders, MD

  Milton S. Hershey Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Hershey Medical Center Manager

Study Record Dates

• First Submitted: September 29, 2020
• First Posted: September 30, 2020
• Study Start: November 1, 2020
• Primary Completion: November 1, 2021
• Study Completion: December 1, 2021
• Last Updated: December 24, 2020

Record last verified: 2020-12

Locations

US (1)