Influenza
Conditions
Keywords
Influenza, Cognition, Attention, Simple Reaction Time, Alertness, Calmness, Contentment, Mood
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.
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.
Interventions
DRUGOseltamivir
Oseltamivir 75mg BID for 5 days
Sponsors
Hoffmann-La Roche
Trial Management Group Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Attention Assessment | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Working Memory Assessment | Change from baseline at Day 4 | Working memory assessed with the Dot Memory Test. The higher the value, the better the working memory. |
| Change in Processing Speed Assessment | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Mood Assessment | 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. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oseltamivir Added to standard of care for influenza
Oseltamivir: Oseltamivir 75mg BID for 5 days | 59 |
| Standard of Care Alone Standard of care for influenza | 63 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Oseltamivir | Standard of Care Alone |
|---|---|---|---|
| Age, Continuous | 34.0 years | 37.0 years | 32.0 years |
| Baseline Symptom Score | 14 symptom score | 13 symptom score | 14 symptom score |
| Body Temperature | 38.1 Degrees centigrade | 38.1 Degrees centigrade | 38.1 Degrees centigrade |
| Cognitive/Mood Conditions ADHD | 1 Participants | 0 Participants | 1 Participants |
| Cognitive/Mood Conditions Anxiety | 2 Participants | 1 Participants | 1 Participants |
| Cognitive/Mood Conditions Depression | 6 Participants | 5 Participants | 1 Participants |
| Cognitive/Mood Conditions None | 113 Participants | 53 Participants | 60 Participants |
| Current Smoker | 21 Participants | 7 Participants | 14 Participants |
| Health Assessment Question | 3 Score | 3 Score | 3 Score |
| Highest Education Level 1 - 3 Years College | 44 Participants | 20 Participants | 24 Participants |
| Highest Education Level Bachelor's Degree | 29 Participants | 16 Participants | 13 Participants |
| Highest Education Level Grade 5 - 11 | 10 Participants | 7 Participants | 3 Participants |
| Highest Education Level High School Graduate | 31 Participants | 12 Participants | 19 Participants |
| Highest Education Level Post-Graduate | 8 Participants | 4 Participants | 4 Participants |
| Influenza Type Strain A | 105 Participants | 53 Participants | 52 Participants |
| Influenza Type Strain B | 17 Participants | 6 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 24 Participants | 12 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 92 Participants | 43 Participants | 49 Participants |
| Region of Enrollment Canada | 122 participants | 59 participants | 63 participants |
| Sex: Female, Male Female | 62 Participants | 29 Participants | 33 Participants |
| Sex: Female, Male Male | 60 Participants | 30 Participants | 30 Participants |
| Time from Symptom Onset | 35.0 hours | 33.8 hours | 36.7 hours |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 59 | 8 / 63 |
| serious Total, serious adverse events | 0 / 59 | 0 / 63 |
Outcome results
Primary
Change in Attention Assessment
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.
Time frame: Change from baseline at Day 4
Population: All randomised subjects for whom data was collected at both baseline and Day 4. Oseltamivir group: baseline data available for 58 of 59 randomised subjects and Day 4 data for 53 subjects (53 subjects analysed). Standard of Care Alone group: baseline data available for 61 of 63 subjects and Day 4 data for 55 subjects (55 subjects analysed).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir | Change in Attention Assessment | -70.0 milliseconds | Standard Error 10.9 |
| Standard of Care Alone | Change in Attention Assessment | -39.7 milliseconds | Standard Error 10.9 |
p-value: 0.049295% CI: [-60.7, -0.1]ANCOVA
Secondary
Change in Processing Speed Assessment
Processing speed assessed with the animal number decoding subtest The lower the value, the better the processing speed
Time frame: Change from baseline at Day 4
Population: All randomized subjects for whom data was collected at both Baseline and Day 4. Oseltamivr Group: Baseline data available for all randomized subjects (59); Day 4 data available for 54 subjects (54 analysed). Standard of Care Alone Group: Baseline data available for all randomized subjects (63); Day 4 data available for 58 subjects (58 analysed).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir | Change in Processing Speed Assessment | -551.9 Millliseconds | Standard Error 77.6 |
| Standard of Care Alone | Change in Processing Speed Assessment | -555.8 Millliseconds | Standard Error 78.2 |
p-value: 0.968595% CI: [-190.1, 197.9]ANCOVA
Secondary
Change in Working Memory Assessment
Working memory assessed with the Dot Memory Test. The higher the value, the better the working memory.
Time frame: Change from baseline at Day 4
Population: All randomised subjects with data collected at both Baseline and Day 4. Oseltamivir Group: Baseline values collected for all randomized subjects (59); Day 4 data available for 54 subjects (54 analysed). Standard of Care Alone Group: Baseline values collected for all randomized subjects (63); Day 4 data available for 58 subjects (58 analysed)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir | Change in Working Memory Assessment | 8.2 Number of correct answers | Standard Error 0.95 |
| Standard of Care Alone | Change in Working Memory Assessment | 4.4 Number of correct answers | Standard Error 0.94 |
p-value: 0.005495% CI: [1.14, 6.42]ANCOVA
Other Pre-specified
Change in Mood Assessment
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.
Time frame: Change from baseline at Day 4
Population: All randomised subjects with data collected at both Baseline and Day 4. Baseline data was available for all randomized subjects in both groups; Day 4 data was available for 54 of 59 randomized subjects in the Oseltamivir Group (54 analysed) and for 58 of 63 randomized subjects in the Standard of Care Alone Group (58 analysed).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir | Change in Mood Assessment | Change in Alertness Assessment | 19.1 millimeter | Standard Error 1.4 |
| Oseltamivir | Change in Mood Assessment | Change in Calmness Assessment | 3.0 millimeter | Standard Error 1.3 |
| Oseltamivir | Change in Mood Assessment | Change in Contentedness Assessment | 16.3 millimeter | Standard Error 1.5 |
| Standard of Care Alone | Change in Mood Assessment | Change in Alertness Assessment | 17.2 millimeter | Standard Error 1.4 |
| Standard of Care Alone | Change in Mood Assessment | Change in Calmness Assessment | 3.6 millimeter | Standard Error 1.2 |
| Standard of Care Alone | Change in Mood Assessment | Change in Contentedness Assessment | 13.0 millimeter | Standard Error 1.5 |
Comparison: Alertness: the higher the value, the greater the alertness.p-value: 0.319595% CI: [-1.9, 5.7]ANCOVA
Comparison: Calmness: the higher the value, the greater the calmness.p-value: 0.721995% CI: [-4.1, 2.9]ANCOVA
Comparison: Contentedness: the higher the value, the greater the contentedness.p-value: 0.116295% CI: [-0.8, 7.4]ANCOVA