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

NCT01546506 | Completed Phase 2 DMC

• 1 other identifier: 2010.654/58
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 39

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.

Conditions

Influenza A Virus Infection

Outcome Measures

Primary Outcomes (1)

• Comparison of viral replication kinetics between the 2 arms

  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

  7 days

Secondary Outcomes (5)

• Percentage of patients with a normalized viral load

  7 days

• Duration and severity of flu symptoms

  7 days

• Frequency, duration and level of replication of the virus in nose samples

  7 days

• Viral resistance and decrease of sensitivity of collected strains

  7 days

• Tolerance of midodrine : incidence of adverse effects

  7 days

Study Arms (2)

Midodrine

EXPERIMENTAL

Midodrine 2.5 mg orally 3 times daily, 5 day-treatment.

Drug: Gutron® treatment

No treatment

NO INTERVENTION

Interventions

Gutron® treatment DRUG

Midodrine 2.5 mg orally 3 times daily, 5 day-treatment.

Midodrine

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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),

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (39)

Cabinet Médical du Dr ALIBERT

Bron, 69500, France

Location

Cabinet Médical du Dr CURE

Bron, 69500, France

Location

Centre d'Investigation Clinique de Lyon

Bron, 69677, France

Location

Cabinet du Dr DAHAN

Decine Charpieu, 69150, France

Location

Cabinet du Dr MADELON

Décine Charpieu, 69150, France

Location

Cabinet Médical du Dr HILLION

Lyon, 69001, France

Location

Cabient Médical du Dr PIOS

Lyon, 69003, France

Location

Cabinet du Dr ATTALI

Lyon, 69003, France

Location

Cabinet du Dr COUTY

Lyon, 69003, France

Location

Hôpital D'Instruction des Armées Desgenettes

Lyon, 69003, France

Location

Cabinet Médical du Dr FORGEOIS

Lyon, 69005, France

Location

Cabinet Médical du Dr TERRASSE

Lyon, 69005, France

Location

Cabinet du Dr THIBAUT

Lyon, 69006, France

Location

Cabinet Médical du Dr BUGEL

Lyon, 69006, France

Location

Cabinet Médical du Dr CHAPDANIEL

Lyon, 69006, France

Location

Cabinet du Dr AKIKI

Lyon, 69007, France

Location

Cabinet du Dr BOURAS

Lyon, 69007, France

Location

Cabinet du Dr GREVE

Lyon, 69007, France

Location

Cabinet du Dr MANOELIAN

Lyon, 69007, France

Location

Cabinet du Dr ROCHE

Lyon, 69007, France

Location

Cabinet du Dr AZULAY TEBOUL

Lyon, 69009, France

Location

Cabinet du Dr DRUT

Lyon, 69009, France

Location

Cabinet Médical du Dr SAINT-OLIVE

Lyon, 69009, France

Location

Cabinet du Dr JACQUET

Meyzieu, 69330, France

Location

Cabinet du Dr FARHAT

Saint-Pierre-de-Chandieu, 69780, France

Location

Cabinet du Dr CHAMPETIER

Saint-Priest, 69800, France

Location

Cabinet Médical du Dr SMIT

Saint-Priest, 69800, France

Location

Cbinet Médical du Dr CEZANNE-BERT

Saint-Priest, 69800, France

Location

Cabinet Médical du Dr DUBOIS

Saint-Symphorien-dOzon, 69360, France

Location

Cabinet du Dr CHAIZE

Vénissieux, 69200, France

Location

Cabinet Médical du Dr MARTIN

Vénissieux, 69200, France

Location

Cabinet Médical du Dr THEOULE

Vénissieux, 69200, France

Location

Cabinet Médical du Dr MOREAU

Villefontaine, 38090, France

Location

Cabinet Médical du Dr BUFFLER

Villeurbanne, 69100, France

Location

Cabinet Médical du Dr KESSOUS

Villeurbanne, 69100, France

Location

Cabinet Médical du Dr MONLOUBOU

Villeurbanne, 69100, France

Location

Cabinet Médical du Dr PERDRIX

Villeurbanne, 69100, France

Location

Cabinet Médical du Dr PILLARS

Villeurbanne, 69100, France

Location

Cabinet Médical du Dr WEBER

Villeurbanne, 69100, France

Location

Study Officials

• Bruno LINA, MD, PhD

  Laboratoire de virologie, Institut de microbiologie, Centre de Biologie et de Pathologie EST, Groupement Hospitalier Est, Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2012
• First Posted: March 7, 2012
• Study Start: February 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: January 8, 2015

Record last verified: 2015-01

Locations

FR (39)