Healthy
Conditions
Keywords
influenza vaccine, cytokines, hormones, progesterone
Brief summary
The purpose of this pilot research project is to look at the effect of the inactivated influenza vaccine (seasonal flu shot) on early signs of immune or germ-fighting response known as cytokines or signal molecules. The investigators also want to see if the timing of vaccine administration has any effect on women's reproductive hormones. The investigators hypothesis is that influenza vaccine given right before ovulation may change the hormone levels usually seen after ovulation. Thi
Detailed description
This study is an open-label, longitudinal study of healthy young women of reproductive age, not on hormonal contraception who receive seasonal inactivated influenza vaccine (IIV). The women will be followed for one menstrual cycle to measure luteinizing hormone surge, estradiol, and progesterone, and then vaccinated with the seasonal inactivated influenza vaccine prior to ovulation during a second month. At the investigator's discretion, or if there is active circulation of influenza virus in Baltimore, the investigators will vaccinate during the first menstrual cycle (prior to ovulation) and then follow for a second menstrual cycle for comparison. After vaccination, they will be followed for cytokine and chemokine responses as well as changes in the concentrations of steroid hormones. This study will evaluate the effect of IIV on inflammatory cytokines and hormonal responses before and after ovulation. Each woman will have 13 visits in addition to a screening visit, and will be followed for 2 complete menstrual cycles.
Interventions
BIOLOGICALSeasonal Inactivated Influenza Vaccine
Quadrivalent seasonal inactivated influenza vaccine, 0.5 mL intramuscularly
Sponsors
Centers for Disease Control and Prevention
Johns Hopkins Bloomberg School of Public Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 39 Years
Healthy volunteers
Yes
Inclusion criteria
* Women 18-39 years of age who are in good health. * Good general health as a result of review of medical history and/or clinical testing at the time of screening. * Available for the duration of the trial. * Willingness to participate in the study as evidenced by signing the informed consent document. * Willing to be abstinent or to use non-hormonal methods of contraception for the duration of the study. * History of normal menstrual cycles (26-35 days in length) for at least 3 months. * Willingness to refrain from routine vaccination (except as administered during study) for the duration of the study.
Exclusion criteria
* Use of contraceptive pills, patch, injection or other hormonal therapies in the preceding 3 months (6 months for DepoProvera) * A history of hypersensitivity, including anaphylaxis to any of the components of IIV or to eggs. * Previous receipt of a same season licensed influenza vaccine. * Pregnancy as determined by a positive urine or serum human choriogonadotropin (β-hCG) test at any point during the study or in the preceding 3 months. * Currently is lactating or breast-feeding. * Fewer than 3 normal menstrual cycles since conclusion of last pregnancy or last use of hormonal birth control. * A history of autoimmune disease, or any other chronic medical condition considered clinically significant by the investigator. * History of HIV, Hepatitis C or active Hepatitis B. * Known immunodeficiency syndrome. * History of Guillain-Barré syndrome. * Use of chronic oral or intravenous administration (≥14 days) of immunosuppressive doses of steroids, i.e., prednisone \>10 mg per day, immunosuppressants or other immune-modifying drugs within 30 days of starting this study. (Use of topical, nasal or inhaled steroids is permitted) * Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to study start or during study. * Receipt of blood or blood-derived products (including immunoglobulin) within 6 months prior to study vaccination. * Receipt of another investigational vaccine or drug within 30 days prior to study start, or during study. * Ongoing, daily use of analgesics or anti-inflammatory medications, including nonsteroidal anti-inflammatories. Occasional use, and use associated with menstrual periods is acceptable.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Levels of Progesterone After Influenza Vaccination | 2 months | To explore whether receipt of IIV during the second week of the menstrual cycle (i.e., the week prior to ovulation) is associated with changes in steroid hormone levels, particularly decreases in progesterone, following ovulation. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cytokine Effect on Reproductive Hormone Levels | 2 months | To explore whether inflammatory cytokine responses to IIV receipt are associated with changes in reproductive and stress hormone levels. |
| Cytokine Responses to Influenza Vaccine | 2 days | Identify optimal biomarkers of the inflammatory response after vaccination. |
Countries
United States
Participant flow
Recruitment details
103 adult female subjects enrolled and 92 completed study over 3 vaccination seasons from 2013-2017. Each participant served as her own control and followed for 2 months: an Inactivated influenza vaccination (IIV) month and a observation/comparator month.
Pre-assignment details
Study specific screening occurred prior to enrollment. 180 screens completed
Participants by arm
| Arm | Count |
|---|---|
| Healthy Women All women are to receive the quadrivalent influenza vaccine
Seasonal Inactivated Influenza Vaccine: Quadrivalent seasonal inactivated influenza vaccine, 0.5 mL intramuscularly | 92 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | Healthy Women |
|---|---|
| Age, Continuous | 28 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 11 Participants |
| Race (NIH/OMB) Black or African American | 54 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 92 participants |
| Sex: Female, Male Female | 92 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 92 |
| other Total, other adverse events | 73 / 92 |
| serious Total, serious adverse events | 0 / 92 |
Outcome results
Primary
Change in Levels of Progesterone After Influenza Vaccination
To explore whether receipt of IIV during the second week of the menstrual cycle (i.e., the week prior to ovulation) is associated with changes in steroid hormone levels, particularly decreases in progesterone, following ovulation.
Time frame: 2 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Women (Vaccine) | Change in Levels of Progesterone After Influenza Vaccination | Progesterone Day 28 | 0.55 ng/ml | Standard Deviation 1.03 |
| Healthy Women (Vaccine) | Change in Levels of Progesterone After Influenza Vaccination | Progesterone Day 11 | 0.73 ng/ml | Standard Deviation 1.4 |
| Healthy Women (Vaccine) | Change in Levels of Progesterone After Influenza Vaccination | Progesterone Day 0 | 0.62 ng/ml | Standard Deviation 1.6 |
| Healthy Women (Vaccine) | Change in Levels of Progesterone After Influenza Vaccination | Progesterone Day 17 | 4.59 ng/ml | Standard Deviation 4.42 |
| Healthy Women (Vaccine) | Change in Levels of Progesterone After Influenza Vaccination | Progesterone Day 21 | 6.72 ng/ml | Standard Deviation 4.59 |
| Healthy Women (Comparator) | Change in Levels of Progesterone After Influenza Vaccination | Progesterone Day 17 | 4.53 ng/ml | Standard Deviation 4.13 |
| Healthy Women (Comparator) | Change in Levels of Progesterone After Influenza Vaccination | Progesterone Day 21 | 6.32 ng/ml | Standard Deviation 3.7 |
| Healthy Women (Comparator) | Change in Levels of Progesterone After Influenza Vaccination | Progesterone Day 28 | 0.92 ng/ml | Standard Deviation 1.98 |
| Healthy Women (Comparator) | Change in Levels of Progesterone After Influenza Vaccination | Progesterone Day 0 | 0.43 ng/ml | Standard Deviation 0.8 |
| Healthy Women (Comparator) | Change in Levels of Progesterone After Influenza Vaccination | Progesterone Day 11 | 0.59 ng/ml | Standard Deviation 0.92 |
Other Pre-specified
Cytokine Effect on Reproductive Hormone Levels
To explore whether inflammatory cytokine responses to IIV receipt are associated with changes in reproductive and stress hormone levels.
Time frame: 2 months
Other Pre-specified
Cytokine Responses to Influenza Vaccine
Identify optimal biomarkers of the inflammatory response after vaccination.
Time frame: 2 days