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

Sponsor
Hospices Civils de Lyon (Other)
Overall Status
Completed
CT.gov ID
NCT01546506
Collaborator
(none)
79
Enrollment
39
Locations
2
Arms
24.9
Duration (Months)
2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
  • Drug: Gutron® treatment
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
79 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (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
Study Start Date :
Feb 1, 2012
Actual Primary Completion Date :
Mar 1, 2014
Actual Study Completion Date :
Mar 1, 2014

Arms and Interventions

Arm Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

  1. Comparison of viral replication kinetics between the 2 arms [7 days]

    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

  1. Percentage of patients with a normalized viral load [7 days]

    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

  2. Duration and severity of flu symptoms [7 days]

  3. Frequency, duration and level of replication of the virus in nose samples [7 days]

  4. Viral resistance and decrease of sensitivity of collected strains [7 days]

  5. Tolerance of midodrine : incidence of adverse effects [7 days]

    Side effects will be checked at each visit and reported for the entire study timeframe.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Locations

Site City State Country Postal Code
1 Cabinet Médical du Dr ALIBERT Bron France 69500
2 Cabinet Médical du Dr CURE Bron France 69500
3 Centre d'Investigation Clinique de Lyon Bron France 69677
4 Cabinet du Dr DAHAN Decine Charpieu France 69150
5 Cabinet du Dr MADELON Décine Charpieu France 69150
6 Cabinet Médical du Dr HILLION Lyon France 69001
7 Cabient Médical du Dr PIOS Lyon France 69003
8 Cabinet du Dr ATTALI Lyon France 69003
9 Cabinet du Dr COUTY Lyon France 69003
10 Hôpital D'Instruction des Armées Desgenettes Lyon France 69003
11 Cabinet Médical du Dr FORGEOIS Lyon France 69005
12 Cabinet Médical du Dr TERRASSE Lyon France 69005
13 Cabinet du Dr THIBAUT Lyon France 69006
14 Cabinet Médical du Dr BUGEL Lyon France 69006
15 Cabinet Médical du Dr CHAPDANIEL Lyon France 69006
16 Cabinet du Dr AKIKI Lyon France 69007
17 Cabinet du Dr BOURAS Lyon France 69007
18 Cabinet du Dr GREVE Lyon France 69007
19 Cabinet du Dr MANOELIAN Lyon France 69007
20 Cabinet du Dr ROCHE Lyon France 69007
21 Cabinet du Dr AZULAY TEBOUL Lyon France 69009
22 Cabinet du Dr DRUT Lyon France 69009
23 Cabinet Médical du Dr SAINT-OLIVE Lyon France 69009
24 Cabinet du Dr JACQUET Meyzieu France 69330
25 Cabinet du Dr CHAMPETIER Saint Priest France 69800
26 Cbinet Médical du Dr CEZANNE-BERT Saint Priest France 69800
27 Cabinet Médical du Dr SMIT Saint-priest France 69800
28 Cabinet Médical du Dr DUBOIS Saint-Symphorien d'Ozon France 69360
29 Cabinet du Dr FARHAT St Pierre de Chandieu France 69780
30 Cabinet du Dr CHAIZE Venissieux France 69200
31 Cabinet Médical du Dr MARTIN Venissieux France 69200
32 Cabinet Médical du Dr THEOULE Venissieux France 69200
33 Cabinet Médical du Dr MOREAU Villefontaine France 38090
34 Cabinet Médical du Dr BUFFLER Villeurbanne France 69100
35 Cabinet Médical du Dr KESSOUS Villeurbanne France 69100
36 Cabinet Médical du Dr MONLOUBOU Villeurbanne France 69100
37 Cabinet Médical du Dr PERDRIX Villeurbanne France 69100
38 Cabinet Médical du Dr PILLARS Villeurbanne France 69100
39 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT01546506
Other Study ID Numbers:
  • 2010.654/58
First Posted:
Mar 7, 2012
Last Update Posted:
Jan 8, 2015
Last Verified:
Jan 1, 2015
Additional relevant MeSH terms:
Virus Diseases

Study Results

No Results Posted as of Jan 8, 2015