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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 is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Hospices Civils de Lyon
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT01546506
First received: March 2, 2012
Last updated: January 14, 2014
Last verified: January 2014
  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.


Estimated Enrollment: 161
Study Start Date: February 2012
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 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
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

Contacts
Contact: Bruno LINA, MD, PhD 472 12 96 17 ext +33 bruno.lina@chu-lyon.fr
Contact: Ségolène GAILLARD 427 85 77 28 ext +33 segolene.gaillard@chu-lyon.fr

Locations
France
Cabinet Médical du Dr ALIBERT Recruiting
Bron, France, 69500
Contact: Delphine ALIBERT, MD         
Principal Investigator: Delphine ALIBERT, MD         
Cabinet Médical du Dr CURE Recruiting
Bron, France, 69500
Contact: Nicole CURE, MD         
Principal Investigator: Nicole CURE, MD         
Centre d'Investigation Clinique de Lyon Recruiting
Bron, France, 69677
Contact: Catherine CORNU, MD         
Contact: Ségolène GAILLARD         
Principal Investigator: Catherine CORNU, MD         
Cabinet du Dr DAHAN Recruiting
Decine Charpieu, France, 69150
Contact: Catherine DAHAN, MD         
Principal Investigator: Catherine DAHAN, MD         
Cabinet du Dr MADELON Recruiting
Décine Charpieu, France, 69150
Contact: Jean MADELON, MD         
Principal Investigator: Jean MADELON, MD         
Cabinet du Dr MANOELIAN Recruiting
Lyon, France, 69007
Contact: Grégoire MANOELIAN, MD         
Principal Investigator: Grégoire MANOELIAN, MD         
Cabinet du Dr AKIKI Recruiting
Lyon, France, 69007
Contact: Louis AKIKI, MD         
Principal Investigator: Louis AKIKI, MD         
Cabinet du Dr ATTALI Recruiting
Lyon, France, 69003
Contact: Eric ATTALI, MD         
Principal Investigator: Eric ATTALI, MD         
Cabinet du Dr AZULAY TEBOUL Recruiting
Lyon, France, 69009
Contact: Elisabeth AZULAY TEBOUL, MD         
Principal Investigator: Elisabeth AZULAY TEBOUL, MD         
Cabinet du Dr BOURAS Recruiting
Lyon, France, 69007
Contact: Chahrazade BOURAS, MD         
Principal Investigator: Chahrazade BOURAS, MD         
Cabinet du Dr COUTY Recruiting
Lyon, France, 69003
Contact: Jeanne COUTY, MD         
Principal Investigator: Jeannne COUTY, MD         
Cabinet du Dr DRUT Recruiting
Lyon, France, 69009
Contact: Lionel DRUT, MD         
Principal Investigator: Lionel DRUT, MD         
Cabinet du Dr GREVE Recruiting
Lyon, France, 69007
Contact: Dominique GREVE, MD         
Principal Investigator: Dominique GREVE, MD         
Hôpital D'Instruction des Armées Desgenettes Recruiting
Lyon, France, 69003
Contact: Christophe LABLANCHE, m         
Principal Investigator: Christophe LABLANCHE, MD         
Cabinet du Dr ROCHE Recruiting
Lyon, France, 69007
Contact: François-Louis ROCHE, MD         
Principal Investigator: François-Louis ROCHE, MD         
Cabient Médical du Dr PIOS Recruiting
Lyon, France, 69003
Contact: Renée PIOS         
Principal Investigator: Renée PIOS, MD         
Cabinet Médical du Dr BUGEL Recruiting
Lyon, France, 69006
Contact: Corinne BUGEL, MD         
Principal Investigator: Corinne BUGEL, MD         
Cabinet Médical du Dr CHAPDANIEL Recruiting
Lyon, France, 69006
Contact: Christian CHAPDANIEL, MD         
Principal Investigator: Christian CHAPDANIEL, MD         
Cabinet Médical du Dr FORGEOIS Recruiting
Lyon, France, 69005
Contact: Jacques FORGEOIS, MD         
Principal Investigator: Jacques FORGEOIS, MD         
Cabinet Médical du Dr HILLION Recruiting
Lyon, France, 69001
Contact: Luc HILLION, MD         
Principal Investigator: Luc HILLION, MD         
Cabinet Médical du Dr SAINT-OLIVE Recruiting
Lyon, France, 69009
Contact: Dominique SAINT-OLIVE, MD         
Principal Investigator: Dominique SAINT-OLIVE, MD         
Cabinet Médical du Dr TERRASSE Recruiting
Lyon, France, 69005
Contact: Patrick TERRASSE, MD         
Principal Investigator: Patrick TERRASSE, MD         
Cabinet du Dr THIBAUT Recruiting
Lyon, France, 69006
Contact: Vincent THIBAUT, MD         
Principal Investigator: Vincent THIBAUT, MD         
Cabinet du Dr JACQUET Recruiting
Meyzieu, France, 69330
Contact: François JACQUET, MD         
Principal Investigator: François JACQUET, MD         
Cabinet du Dr CHAMPETIER Recruiting
Saint Priest, France, 69800
Contact: Yvan CHAMPETIER, MD         
Principal Investigator: Yvan CHAMPETIER, MD         
Cbinet Médical du Dr CEZANNE-BERT Recruiting
Saint Priest, France, 69800
Contact: Roland CEZANNE-BERT, MD         
Principal Investigator: Roland CEZANNE-BERT, MD         
Cabinet Médical du Dr SMIT Recruiting
Saint-priest, France, 69800
Contact: Gérard SMIT, MD         
Principal Investigator: Gérard SMIT, MD         
Cabinet Médical du Dr DUBOIS Recruiting
Saint-Symphorien d'Ozon, France, 69360
Contact: Jean-Pierre DUBOIS, MD         
Principal Investigator: Jean-Pierre DUBOIS, MD         
Cabinet du Dr FARHAT Recruiting
St Pierre de Chandieu, France, 69780
Contact: Salam FARHAT, MD         
Principal Investigator: Salam FARHAT, MD         
Cabinet Médical du Dr THEOULE Recruiting
Venissieux, France, 69200
Contact: Jean THEOULE, MD         
Principal Investigator: Jean THEOULE, MD         
Cabinet Médical du Dr MARTIN Recruiting
Venissieux, France, 69200
Contact: Xavier MARTIN, MD         
Principal Investigator: Xavier MARTIN, MD         
Cabinet du Dr CHAIZE Recruiting
Venissieux, France, 69200
Contact: Marie-Christine CHAIZE, MD         
Principal Investigator: Marie-Christine CHAIZE, MD         
Cabinet Médical du Dr MOREAU Recruiting
Villefontaine, France, 38090
Contact: Alain MOREAU, MD         
Principal Investigator: Alain MOREAU, MD         
Cabinet Médical du Dr BUFFLER Recruiting
Villeurbanne, France, 69100
Contact: Philippe BUFFLER, MD         
Principal Investigator: Philippe BUFFLER, MD         
Cabinet Médical du Dr KESSOUS Recruiting
Villeurbanne, France, 69100
Contact: Martine KESSOUS, MD         
Principal Investigator: Martine KESSOUS, MD         
Cabinet Médical du Dr MONLOUBOU Recruiting
Villeurbanne, France, 69100
Contact: Damien MONLOUBOU, MD         
Principal Investigator: Damien MONLOUBOU, MD         
Cabinet Médical du Dr PERDRIX Recruiting
Villeurbanne, France, 69100
Contact: Corinne PERDRIX, MD         
Principal Investigator: Corinne PERDRIX, MD         
Cabinet Médical du Dr PILLARS Recruiting
Villeurbanne, France, 69100
Contact: Michel PILLARS, MD         
Principal Investigator: Michel PILLARS, MD         
Cabinet Médical du Dr WEBER Recruiting
Villeurbanne, France, 69100
Contact: Xavier-Jacques WEBER, MD         
Principal Investigator: Xavier-Jacques WEBER, MD         
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

No publications provided

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 14, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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

ClinicalTrials.gov processed this record on November 20, 2014