Immune and Hormone Response to Influenza Vaccine

• Sponsor: Johns Hopkins Bloomberg School of Public Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT01978262
• Collaborator: Centers for Disease Control and Prevention (U.S. Fed)
• Enrollment: 103
• Location: 1
• Arm: 1
• Duration (Months): 46
• Patients Per Site Per Month: 2.2

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Healthy	Biological: Seasonal Inactivated Influenza Vaccine	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Pilot Study of the Immune Response to Influenza Vaccination and Effect on Reproductive Hormones
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Aug 1, 2017
• Actual Study Completion Date: Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Other: healthy woman All women are to receive the quadrivalent influenza vaccine	Biological: Seasonal Inactivated Influenza Vaccine; Quadrivalent seasonal inactivated influenza vaccine, 0.5 mL intramuscularly; Other Names: FluZone

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. Cytokine Responses to Influenza Vaccine [2 days]

   Identify optimal biomarkers of the inflammatory response after vaccination.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 39 Years
• Sexes Eligible for Study: Female
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Immunization Research; Johns Hopkins Bloomberg School of Public Health	Baltimore	Maryland	United States	21205

Sponsors and Collaborators

• Johns Hopkins Bloomberg School of Public Health
• Centers for Disease Control and Prevention

Investigators

• Principal Investigator: Kawsar R Talaat, MD, Johns Hopkins Bloomberg School of Public Health
• Principal Investigator: Karen Broder, M.D., Centers for Disease Control and Prevention

Study Documents (Full-Text)

• Statistical Analysis Plan - Jan 24, 2018
• Study Protocol - Jan 24, 2018

More Information

Additional Information:

• Center for Immunization Research Website
• Click here for information about enrolling in this study

Publications

None provided.

• Responsible Party: Johns Hopkins Bloomberg School of Public Health
• ClinicalTrials.gov Identifier: NCT01978262
• Other Study ID Numbers: CIR 292; 200-2012-53664-002
• First Posted: Nov 7, 2013
• Last Update Posted: Dec 27, 2018
• Last Verified: Dec 1, 2018

• Keywords provided by Johns Hopkins Bloomberg School of Public Health: influenza vaccine; cytokines; hormones; progesterone
• Additional relevant MeSH terms: Influenza, Human

Study Results

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 Detail	Study specific screening occurred prior to enrollment. 180 screens completed

Arm/Group Title	Healthy Women
Arm/Group Description	All women are to receive the quadrivalent influenza vaccine Seasonal Inactivated Influenza Vaccine: Quadrivalent seasonal inactivated influenza vaccine, 0.5 mL intramuscularly
Period Title: Overall Study
STARTED	103
COMPLETED	92
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Healthy Women
Arm/Group Description	All women are to receive the quadrivalent influenza vaccine Seasonal Inactivated Influenza Vaccine: Quadrivalent seasonal inactivated influenza vaccine, 0.5 mL intramuscularly
Overall Participants	92
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	28
Sex: Female, Male (Count of Participants)
Female	92 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 6.5%
Not Hispanic or Latino	86 93.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.1%
Asian	11 12%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	54 58.7%
White	23 25%
More than one race	2 2.2%
Unknown or Not Reported	1 1.1%
Region of Enrollment (participants) [Number]
United States	92 100%

Outcome Measures

1. Primary Outcome

Title	Change in Levels of Progesterone After Influenza Vaccination
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy Women (Vaccine)	Healthy Women (Comparator)
Arm/Group Description	All women are to receive the quadrivalent influenza vaccine Seasonal Inactivated Influenza Vaccine: Quadrivalent seasonal inactivated influenza vaccine, 0.5 mL intramuscularly	All women are to receive the quadrivalent influenza vaccine Seasonal Inactivated Influenza Vaccine: Quadrivalent seasonal inactivated influenza vaccine, 0.5 mL intramuscularly Comparator Month
Measure Participants	92	92
Progesterone Day 0	0.62 (1.60)	0.43 (0.80)
Progesterone Day 11	0.73 (1.40)	0.59 (0.92)
Progesterone Day 17	4.59 (4.42)	4.53 (4.13)
Progesterone Day 21	6.72 (4.59)	6.32 (3.70)
Progesterone Day 28	0.55 (1.03)	0.92 (1.98)

2. Other Pre-specified Outcome

Title	Cytokine Effect on Reproductive Hormone Levels
Description	To explore whether inflammatory cytokine responses to IIV receipt are associated with changes in reproductive and stress hormone levels.
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Other Pre-specified Outcome

Title	Cytokine Responses to Influenza Vaccine
Description	Identify optimal biomarkers of the inflammatory response after vaccination.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	7 days after vaccination, up to 2 months
Arm/Group Title	Healthy Women
Arm/Group Description	All women are to receive the quadrivalent influenza vaccine Seasonal Inactivated Influenza Vaccine: Quadrivalent seasonal inactivated influenza vaccine, 0.5 mL intramuscularly
All Cause Mortality
	Healthy Women
	Affected / at Risk (%)	# Events
Total	0/92 (0%)
Serious Adverse Events
	Healthy Women
	Affected / at Risk (%)	# Events
Total	0/92 (0%)
Other (Not Including Serious) Adverse Events
	Healthy Women
	Affected / at Risk (%)	# Events
Total	73/92 (79.3%)
Immune system disorders
Chills	2/92 (2.2%)	2
Headache	23/92 (25%)	31
Malaise	11/92 (12%)	11
Musculoskeletal and connective tissue disorders
Myalgia	10/92 (10.9%)	10
Skin and subcutaneous tissue disorders
Ecchymosis	2/92 (2.2%)	2
Eythema	9/92 (9.8%)	9
Induration	9/92 (9.8%)	9
Pain	62/92 (67.4%)	72
Pruritis	2/92 (2.2%)	2
Swelling	9/92 (9.8%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.