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Confirmation of the Antiviral Effects of Midodrine Identified With a Gene Expression Signature-based Screening of Inluenza A Virus Infected Cells (FLUMED)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT01546506
First received: March 2, 2012
Last updated: January 7, 2015
Last verified: January 2015
  Purpose

Rationale:

Classical antiviral therapies target viral proteins and are consequently subject to resistance. To counteract this limitation, alternative strategies have been developed that target cellular factors. We hypothesized that such an approach could also be useful to identify broad-spectrum antivirals. The influenza A virus was used as a model for its viral diversity and because of the need to develop therapies against unpredictable viruses as recently underlined by the H1N1 pandemic. Gene-expression signature-based screening identified broadly effective influenza A antivirals. Midodrine showed great results in inhibiting viral growth and was the most suited to confirm its efficacy in vivo.

The main objective of the study is to assess the efficacy of midodrine taken at usual recommended dose (7.5mg/day) versus no treatment on viral replication kinetics of virus Influenza A.

Secondary objectives: evaluation of the number of patients with a normalized viral load 2, 3 5 and 7 days post-treatment; description of the anti-viral efficacy of midodrine defined as the delay to obtain a prolonged negativity of viral RNA; description of the tolerance of midodrine, evaluation of the clinical response to study treatment; evaluation of the dynamic of viral replication; analysis of the frequency of emergence of mutants and associated resistance.

Methods:

This is a multicenter, randomized, open-label study comparing patients aged 18 to 65 years infected by influenza A virus. Nasopharyngeal washing will be performed at day 0 (randomization), 2, 3, 5 to show the viral replication evolution.

161 patients will be randomized as follows :

  • Arm 1 : Midodrine, 2.5 mg, 3 times a day
  • Arm 2 : No treatment The recruitment is performed by general practitioners in the Lyon area.

Condition Intervention Phase
Influenza A Virus Infection
Drug: Gutron® treatment
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Confirmation of the Antiviral Effects of Midodrine Identified With a Gene Expression Signature-based Screening of Inluenza A Virus Infected Cells

Resource links provided by NLM:


Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:
  • Comparison of viral replication kinetics between the 2 arms [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Comparison of the viral load slopes for 7 days post-study treatment start. Viral load will be measured at day 0, 2, 3, 5, and 7


Secondary Outcome Measures:
  • Percentage of patients with a normalized viral load [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    A normal viral load is defined as a value below the positive threshold of 3 in RT-qPCR at day 2, 3, 5 and 7

  • Duration and severity of flu symptoms [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Frequency, duration and level of replication of the virus in nose samples [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Viral resistance and decrease of sensitivity of collected strains [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Tolerance of midodrine : incidence of adverse effects [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Side effects will be checked at each visit and reported for the entire study timeframe.


Enrollment: 79
Study Start Date: February 2012
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Midodrine
Midodrine 2.5 mg orally 3 times daily, 5 day-treatment.
Drug: Gutron® treatment
Midodrine 2.5 mg orally 3 times daily, 5 day-treatment.
No Intervention: No treatment

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • men and women aged 18 to 65 years,
  • with no long-term illness,
  • presenting flu-like symptoms for less than 42 hours (nasal congestion, sore throat, muscle soreness, asthenia, headache, chills/sweating, fever…),
  • infection with influenza A virus confirmed with a quick diagnostic test,
  • outpatient care,
  • must provide signed and informed consent,
  • beneficiary of a health insurance.

Exclusion Criteria:

  • severe form of flu,
  • pregnant women or positive pregnancy test,
  • breastfeeding women,
  • women of childbearing-potential with no efficient contraceptive,
  • history of chronic respiratory disease : asthma or chronic obstructive pulmonary disease,
  • renal failure,
  • Raynaud's disease,
  • history of epilepsy, confusion, hallucinations or of psychoneurotic state,
  • patients with an increased cardiovascular risk (> 20% according to the Framingham scale) or with a cardiovascular history,
  • patients having a congestive heart failure, swollen legs or a posture hypotension,
  • patients who received a influenza vaccine for seasons 2011-2012 or 2012-2013,
  • known hypersensitivity to any component of the treatment,
  • topical use of nasal decongestant (except physiological serum),
  • use of steroids, immunosuppressive or antipsychotics drugs (including treatments for nausea),
  • use of indirect sympathomimetics drugs (ephedrine, methylphenidate, phenylephrine, pseudoephedrine),
  • use of dopaminergic ergot alkaloids (bromocriptine, cabergoline, lisuride, pergolide) or vasoconstrictor ergot alkaloids (dihydroergotamine, ergotamine, methylergométrine, methylsergide),
  • known hypertension treated or not,
  • history of bradycardia,
  • history of urinary retention,
  • severe cardiopathy,
  • acute angle-closure glaucoma,
  • severe obliterative vasculopathy,
  • vasospasm,
  • thyrotoxicosis,
  • pheochromocytoma,
  • history of angina pectoris,
  • use of guanethidine and related, iproniazide (non selective MAOIs), alpha-blockers and digitalis drugs
  • use of neuraminidase inhibitors: oseltamivir, zanamivir; and M2 proton-selective ion channel inhibitors: amantadine and rimantadine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01546506

Locations
France
Cabinet Médical du Dr ALIBERT
Bron, France, 69500
Cabinet Médical du Dr CURE
Bron, France, 69500
Centre d'Investigation Clinique de Lyon
Bron, France, 69677
Cabinet du Dr DAHAN
Decine Charpieu, France, 69150
Cabinet du Dr MADELON
Décine Charpieu, France, 69150
Cabinet Médical du Dr HILLION
Lyon, France, 69001
Cabient Médical du Dr PIOS
Lyon, France, 69003
Cabinet du Dr ATTALI
Lyon, France, 69003
Cabinet du Dr COUTY
Lyon, France, 69003
Hôpital D'Instruction des Armées Desgenettes
Lyon, France, 69003
Cabinet Médical du Dr FORGEOIS
Lyon, France, 69005
Cabinet Médical du Dr TERRASSE
Lyon, France, 69005
Cabinet du Dr THIBAUT
Lyon, France, 69006
Cabinet Médical du Dr BUGEL
Lyon, France, 69006
Cabinet Médical du Dr CHAPDANIEL
Lyon, France, 69006
Cabinet du Dr AKIKI
Lyon, France, 69007
Cabinet du Dr BOURAS
Lyon, France, 69007
Cabinet du Dr GREVE
Lyon, France, 69007
Cabinet du Dr MANOELIAN
Lyon, France, 69007
Cabinet du Dr ROCHE
Lyon, France, 69007
Cabinet du Dr AZULAY TEBOUL
Lyon, France, 69009
Cabinet du Dr DRUT
Lyon, France, 69009
Cabinet Médical du Dr SAINT-OLIVE
Lyon, France, 69009
Cabinet du Dr JACQUET
Meyzieu, France, 69330
Cabinet du Dr CHAMPETIER
Saint Priest, France, 69800
Cbinet Médical du Dr CEZANNE-BERT
Saint Priest, France, 69800
Cabinet Médical du Dr SMIT
Saint-priest, France, 69800
Cabinet Médical du Dr DUBOIS
Saint-Symphorien d'Ozon, France, 69360
Cabinet du Dr FARHAT
St Pierre de Chandieu, France, 69780
Cabinet du Dr CHAIZE
Venissieux, France, 69200
Cabinet Médical du Dr MARTIN
Venissieux, France, 69200
Cabinet Médical du Dr THEOULE
Venissieux, France, 69200
Cabinet Médical du Dr MOREAU
Villefontaine, France, 38090
Cabinet Médical du Dr BUFFLER
Villeurbanne, France, 69100
Cabinet Médical du Dr KESSOUS
Villeurbanne, France, 69100
Cabinet Médical du Dr MONLOUBOU
Villeurbanne, France, 69100
Cabinet Médical du Dr PERDRIX
Villeurbanne, France, 69100
Cabinet Médical du Dr PILLARS
Villeurbanne, France, 69100
Cabinet Médical du Dr WEBER
Villeurbanne, France, 69100
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
Principal Investigator: Bruno LINA, MD, PhD Laboratoire de virologie, Institut de microbiologie, Centre de Biologie et de Pathologie EST, Groupement Hospitalier Est, Hospices Civils de Lyon
  More Information

Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT01546506     History of Changes
Other Study ID Numbers: 2010.654/58 
Study First Received: March 2, 2012
Last Updated: January 7, 2015
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Virus Diseases
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Respiratory Tract Infections
Respiratory Tract Diseases
Antiviral Agents
Midodrine
Anti-Infective Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Vasoconstrictor Agents
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 27, 2016