Effect of Oseltamivir on Cognitive Function in Subjects With Influenza (FOCUS)

• ClinicalTrials.gov Identifier: NCT01249833
• Recruitment Status: Completed
• First Posted: November 30, 2010
• Results First Posted: March 9, 2017
• Last Update Posted: March 9, 2017
• Sponsor: Trial Management Group Inc.
• Collaborator: Hoffmann-La Roche
• Information provided by (Responsible Party): Trial Management Group Inc.

Study Description

Brief Summary:

This study has been designed to determine if subjects treated with oseltamivir in addition to standard of care treatment for influenza demonstrate a greater improvement in attention / working memory / processing speed / mood as compared to subjects receiving standard of care alone. The cognitive tests employed are objective measures developed and administered online by HeadMinder Inc.

Condition or disease	Intervention/treatment	Phase
Influenza	Drug: Oseltamivir	Phase 4

Detailed Description:

Primary Objective:

To determine if subjects treated with oseltamivir in addition to standard of care treatment for influenza demonstrate a greater improvement in attention as compared to subjects receiving standard of care alone.

Secondary Objectives:

To determine if subjects treated with oseltamivir in addition to standard of care treatment for influenza demonstrate a greater improvement in working memory and processing speed as compared to subjects receiving standard of care alone.

Supportive Objectives:

1. To determine if subjects treated with oseltamivir in addition to standard of care treatment for influenza demonstrate a greater improvement in self-rated alertness as compared to subjects receiving standard of care alone.
2. To determine if subjects treated with oseltamivir in addition to standard of care treatment for influenza demonstrate a greater improvement in self-rated calmness and contentment as compared to subjects receiving standard of care alone.
3. To determine if there is a correlation between the rate of improvement in symptom scores and the rate of change in attention and working memory.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 122 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: Open Label
• Primary Purpose: Treatment
• Official Title: Randomised, Open-label, Multi-Centre, Phase IV Study Assessing the Effect of Oseltamivir Treatment on Cognitive Function in Subjects With Confirmed Influenza Virus Infection
• Study Start Date: November 2010
• Actual Primary Completion Date: April 2012
• Actual Study Completion Date: April 2012

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Oseltamivir; Added to standard of care for influenza	Drug: Oseltamivir; Oseltamivir 75mg BID for 5 days; Other Name: Tamiflu
No Intervention: Standard of care alone; Standard of care for influenza

Outcome Measures

Primary Outcome Measures :

1. Change in Attention Assessment [ Time Frame: Change from baseline at Day 4 ]

   Attention assessed using simple reaction time measured in milliseconds. Simple reaction time calculated as the mean of the following 2 sub-tests:

   • Reaction Time Subtest
   • Cued Reaction Time Subtest

   The lower the value, the better the attention.

Secondary Outcome Measures :

1. Change in Working Memory Assessment [ Time Frame: Change from baseline at Day 4 ]

   Working memory assessed with the Dot Memory Test.

   The higher the value, the better the working memory.

2. Change in Processing Speed Assessment [ Time Frame: Change from baseline at Day 4 ]

   Processing speed assessed with the animal number decoding subtest

   The lower the value, the better the processing speed

Other Outcome Measures:

1. Change in Mood Assessment [ Time Frame: Change from baseline at Day 4 ]

   Mood was assessed using the Bond-Lader 10 cm (100 mm) visual analogue scales for mood (16 scales in total); factored for alertness (mean of 9 scales), calmness (mean of 2 scales) and contentment (mean of 5 scales).

   The range in score for each scale and for each factor (alertness, calmness and contentment) was 0 - 100 mm.

   Each scale was anchored such that the lower the value, the better the mood.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Adult men and women, 18 - 65 years of age (inclusive)

2. Indicative symptoms/signs of uncomplicated acute illness due to influenza infection (A or B strains) that started within a maximum of 2 days prior to Visit 1 as per the Tamiflu® Canadian product label. Signs and symptoms may include the following:

   • Fever
   • Respiratory symptoms (cough, coryza, sore throat, rhinitis)
   • Constitutional symptoms (headache, malaise, myalgia, sweats and/or chills, fatigue)
3. Positive rapid antigen test for influenza (A or B strains) at Visit 1
4. Negative urine pregnancy test at Visit 1 for women of childbearing potential; women of childbearing potential who are sexually active must agree to use a suitable form of contraception during the study. Acceptable birth control measures include: hysterectomy, birth control pills, tubal ligation, intrauterine device, hormonal injections and implants, double barrier methods (such as a condom with a diaphragm or a condom with spermicide), and abstinence. Oral contraceptives must be in stable use for 2 or more cycles prior to screening. Intrauterine device (IUD) must be in use at least 30 days prior to study drug administration. Barrier methods must be in use at least 14 days prior to study drug administration.

5. Subjects must:

   • have daily access to a computer at home with: internet access (preferably high-speed for optimal performance but dial-up can be used as well); Microsoft operating system; Internet Explorer browser capability and an e-mail account. A Macintosh (Mac) computer cannot be used.
   • be capable of and willing to complete the required online assessments in English according to the protocol schedule
   • be willing to abstain from the use of an antiviral medication if they are randomised to the standard of care treatment arm
   • have provided written informed consent prior to the initiation of any study procedures

Exclusion Criteria:

1. More than 2 days since the onset of influenza symptoms
2. Subjects who, in the Investigator's judgment, require treatment with an antiviral medication as per the Canadian "Clinical Recommendations for Patients Presenting with Respiratory Symptoms During the 2009 - 2010 Influenza Season" (see Appendix D)
3. Clinical suspicion of infection with a respiratory virus other than influenza
4. Any medical condition that is sufficiently severe or unstable such that the subject is considered to be at imminent risk of requiring hospitalisation
5. History of conditions that may potentially affect cognitive function during the study, such as underlying neurologic conditions, depression or depressive disorders (unless the condition and treatment have been stable for 3 months), seasonal affective disorder (SAD), or any other cognitive impairment or dementia
6. Intermittent use of sedative-hypnotics; subjects who have been taking a fixed dose of a sedative-hypnotic every day for a period of at least 30 days may be included provided that they continue the same regimen throughout the study.
7. Intermittent or chronic use of psychiatric medications (with the exception of antidepressants that have been stable for 3 months) or anti-epileptic drugs
8. Nursing home residents
9. Known allergy to oseltamivir phosphate or any of the inactive ingredients of Tamiflu®
10. Women who are pregnant, or planning to become pregnant, or who are lactating
11. Current alcohol or drug abuse or substance dependence
12. Participation in another clinical trial with an investigational drug within the last 30 days
13. Patients vaccinated for influenza within 6 months of study enrollment
14. In the Investigator's judgment, the subject will not be able to adhere to the protocol requirements or is not suitable for study participation for any reason

Contacts and Locations

Locations

Canada, British Columbia

Dr. Collette

Vancouver, British Columbia, Canada

Dr. Lai

Vancouver, British Columbia, Canada

Canada, Newfoundland and Labrador

Topsail Road Medical Clinic

St. John's, Newfoundland and Labrador, Canada

Canada, Ontario

Moran Medical Centre

Collingwood, Ontario, Canada

Dr. Kanani

Etobicoke, Ontario, Canada

Dr. Herman

London, Ontario, Canada

Milestone Research

London, Ontario, Canada

SKDS Research Inc

Newmarket, Ontario, Canada

Family First Medical Centre

Orleans, Ontario, Canada

Steeple Hill Medical Centre

Pickering, Ontario, Canada, L1V 2A6

Dr. Martyn Chilvers - London Road Diagnostic Clinic and Medical Centre

Sarnia, Ontario, Canada

Dr. Michael O'Mahony - London Road Diagnostic Clinic and Medical Centre

Sarnia, Ontario, Canada

DCTM Clinical Trials Group Ltd.

Strathroy, Ontario, Canada

Dr. Gupta

Toronto, Ontario, Canada

Devonshire Clinical Research Inc.

Woodstock, Ontario, Canada

Canada, Saskatchewan

Regina Medical Centre

Regina, Saskatchewan, Canada, S4P 3X1

Sponsors and Collaborators

Trial Management Group Inc.

Hoffmann-La Roche

Investigators

• Principal Investigator: Dr. O'Mahony, M.D.; London Road Diagnostic Clinic and Medical Centre

More Information

• Responsible Party: Trial Management Group Inc.
• ClinicalTrials.gov Identifier: NCT01249833
• Other Study ID Numbers: CAI-001-10
• First Posted: November 30, 2010
• Results First Posted: March 9, 2017
• Last Update Posted: March 9, 2017
• Last Verified: January 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Trial Management Group Inc.:

Influenza; Cognition; Attention; Simple Reaction Time; Alertness; Calmness; Contentment; Mood

Additional relevant MeSH terms:

Influenza, Human; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Oseltamivir; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action