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

Influenza A Virus Infection Clinical Trial

— FLUMED  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01546506
• Other study ID #: 2010.654/58
• Status: Completed
• Phase: Phase 2
• First received: March 2, 2012
• Last updated: January 7, 2015
• Start date: February 2012
• Est. completion date: March 2014

Study information

• Verified date: January 2015
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Influenza A Virus Infection
• Influenza, Human
• Virus Diseases

Intervention

Drug:
• Gutron® treatment
Midodrine 2.5 mg orally 3 times daily, 5 day-treatment.

Locations

Country	Name	City	State
France	Cabinet Médical du Dr ALIBERT	Bron
France	Cabinet Médical du Dr CURE	Bron
France	Centre d'Investigation Clinique de Lyon	Bron
France	Cabinet du Dr DAHAN	Decine Charpieu
France	Cabinet du Dr MADELON	Décine Charpieu
France	Cabient Médical du Dr PIOS	Lyon
France	Cabinet du Dr AKIKI	Lyon
France	Cabinet du Dr ATTALI	Lyon
France	Cabinet du Dr AZULAY TEBOUL	Lyon
France	Cabinet du Dr BOURAS	Lyon
France	Cabinet du Dr COUTY	Lyon
France	Cabinet du Dr DRUT	Lyon
France	Cabinet du Dr GREVE	Lyon
France	Cabinet du Dr MANOELIAN	Lyon
France	Cabinet du Dr ROCHE	Lyon
France	Cabinet du Dr THIBAUT	Lyon
France	Cabinet Médical du Dr BUGEL	Lyon
France	Cabinet Médical du Dr CHAPDANIEL	Lyon
France	Cabinet Médical du Dr FORGEOIS	Lyon
France	Cabinet Médical du Dr HILLION	Lyon
France	Cabinet Médical du Dr SAINT-OLIVE	Lyon
France	Cabinet Médical du Dr TERRASSE	Lyon
France	Hôpital D'Instruction des Armées Desgenettes	Lyon
France	Cabinet du Dr JACQUET	Meyzieu
France	Cabinet du Dr CHAMPETIER	Saint Priest
France	Cbinet Médical du Dr CEZANNE-BERT	Saint Priest
France	Cabinet Médical du Dr SMIT	Saint-priest
France	Cabinet Médical du Dr DUBOIS	Saint-Symphorien d'Ozon
France	Cabinet du Dr FARHAT	St Pierre de Chandieu
France	Cabinet du Dr CHAIZE	Venissieux
France	Cabinet Médical du Dr MARTIN	Venissieux
France	Cabinet Médical du Dr THEOULE	Venissieux
France	Cabinet Médical du Dr MOREAU	Villefontaine
France	Cabinet Médical du Dr BUFFLER	Villeurbanne
France	Cabinet Médical du Dr KESSOUS	Villeurbanne
France	Cabinet Médical du Dr MONLOUBOU	Villeurbanne
France	Cabinet Médical du Dr PERDRIX	Villeurbanne
France	Cabinet Médical du Dr PILLARS	Villeurbanne
France	Cabinet Médical du Dr WEBER	Villeurbanne

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Percentage of patients with a normalized viral load	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	7 days	No
Secondary	Duration and severity of flu symptoms		7 days	No
Secondary	Frequency, duration and level of replication of the virus in nose samples		7 days	No
Secondary	Viral resistance and decrease of sensitivity of collected strains		7 days	No
Secondary	Tolerance of midodrine : incidence of adverse effects	Side effects will be checked at each visit and reported for the entire study timeframe.	7 days	Yes