SLVP025: The Influence of Chronic CMV Infection on Influenza Vaccine Responses

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02134184
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Enrollment: 78
• Location: 1
• Arms: 3
• Duration (Months): 2
• Patients Per Site Per Month: 38.9

Study Details

Study Description

Brief Summary

In this study we are trying to understand whether previous infection with a particular virus, namely cytomegalovirus (CMV), influences the ability of the immune system to respond to new infections or vaccinations with age.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus Infections; Influenza	Biological: Fluzone® 2012-2013 Formula NDC No 498281-012-50	Phase 4

Detailed Description

The investigators want to compare the T- and B-cell response to conventional intramuscular trivalent influenza vaccine (TIV) in elderly individuals dependent on the presence and duration of CMV infection by analyses of vaccine-induced plasmablasts, antibodies and antigen-specific T cells. Healthy volunteers, > 60 years of age, will be identified by the Stanford Blood Center based on their history of positive or negative CMV serologies. Baseline blood samples will be drawn from all study participants prior to immunization. All participants will receive a single dose of 2012-2013 licensed TIV. Volunteers will complete 3 study visits at Day 0, Day 7 and Day 28.

Study Design

• Study Type: Interventional
• Actual Enrollment: 78 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: The Influence of Chronic Cytomegalovirus Infection on Influenza Vaccine Responses
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CMV negative group Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50	Biological: Fluzone® 2012-2013 Formula NDC No 498281-012-50; This vaccine is given intramuscularly; Other Names: Trivalent inactivated influenza vaccine (TIV)
Experimental: CMV positive group Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50	Biological: Fluzone® 2012-2013 Formula NDC No 498281-012-50; This vaccine is given intramuscularly; Other Names: Trivalent inactivated influenza vaccine (TIV)
Experimental: Recent CMV Converters Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50	Biological: Fluzone® 2012-2013 Formula NDC No 498281-012-50; This vaccine is given intramuscularly; Other Names: Trivalent inactivated influenza vaccine (TIV)

Outcome Measures

Primary Outcome Measures

1. Number of Participants From Each Arm Who Received Influenza Vaccine [Day 0 to Day 28]

Secondary Outcome Measures

1. Number of Participants With Related Adverse Events [Day 0 to Day 28]

Other Outcome Measures

1. To Compare the T- and B-cell Response to Licensed IM TIV in Elderly Individuals Dependent on the Presence and Duration of CMV Infection by Analyses of Vaccine-induced Plasmablasts, Antibodies and Antigen-specific T Cells [Day 0 to Day 28]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Otherwise healthy, ambulatory adult 60 years of age or above.

• Self-identified by a participant after notification by Stanford Blood Center (SBC) of their group assignment based review of SBC CMV data:

• CMV-negative: Donor has donated at least twice during the last 3 years AND donor's most recent two donations tested CMV antibody negative.

• CMV positive longstanding infection: Donor has donated at least once within the "recent" timeframe (past three years) AND donor's most recent donation tested CMV antibody positive AND donor had at least one donation prior to 2000 that tested CMV antibody positive.

• Recent CMV converters: Donor has donated at least once within the "recent" timeframe (past three years) AND donor's most recent two donations tested CMV antibody positive AND donor had at least two CMV negative donations in the past.

• Willing to complete the informed consent process.

• Availability for follow-up for the planned duration of the study at least 28 days after immunization.

• Acceptable medical history by review of inclusion/exclusion criteria and vital signs.

Exclusion Criteria:

• Prior off-study vaccination with the current 2012-2013 seasonal influenza vaccine

• Allergy to egg or egg products, or to vaccine components or thimerosal (TIV multidose vials only)

• Life-threatening reactions to previous influenza vaccinations.

• Active systemic or serious concurrent illness, including febrile illness on the day of vaccination

• Weight less than 110 lbs

• History of immunodeficiency (including HIV infection)

• Known or suspected impairment of immunologic function, including, but not limited to, clinically significant liver disease, diabetes mellitus treated with insulin, moderate to severe renal disease, or any other chronic disorder which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol.

• Blood pressure >150 systolic or >95 diastolic at first study visit

• Hospitalization in the past year for congestive heart failure or emphysema.

• History of chronic Hepatitis B or C.

• Recent or current use of immunosuppressive medication, including systemic glucocorticoids (corticosteroid nasal sprays and topical steroids are permissible in all groups)

• Malignancy, other than squamous cell or basal cell skin cancer (includes solid tumors such as breast cancer or prostate cancer with recurrence in the past year, and any hematologic cancer such as leukemia).

• Autoimmune disease (including rheumatoid arthritis treated with immunosuppressive medication such as Plaquenil, methotrexate, prednisone, Enbrel) which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol.

• History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year

• Use of any anti-coagulation medication such as Coumadin or Lovenox, or anti-platelet agents such as aspirin (except up to 325 mg aspirin per day), Plavix, or Aggrenox must be reviewed by investigator to determine if this would affect the volunteer's safety.

• Receipt of blood or blood products within the past 6 months or planned receipt of blood products prior to completion of study visits.

• Medical or psychiatric condition or occupational responsibilities that preclude participant compliance with the protocol

• Inactivated vaccine 14 days prior to vaccination or planned non-study vaccination prior to completion of Visit 03 (~Day 28 after the study vaccination)

• Live, attenuated vaccine within 60 days of vaccination or planned non-study vaccination prior to completion of Visit 03 (~Day 28 after the study vaccination)

• Need an allergy immunization (that cannot be postponed) during the study period V01 to V03 (~Day 28)

• History of Guillain-Barré Syndrome

• Use of investigational agents within 30 days prior to enrollment or planned use of investigational agents prior to completion of study visits

• Donation of the equivalent of a unit of whole blood within 6 weeks or a unit of platelets within 2 weeks prior to enrollment or planned blood donation prior to completion of study visits.

• Any condition which, in the opinion of the investigator, might interfere with volunteer safety, study objectives or the ability of the participant to understand or comply with the study protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University
• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Cornelia L Dekker, MD, Stanford University
• Principal Investigator: Jorg J Goronzy, MD, PhD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Stanford LPCH Vaccine Program Clinical Trials Website

Publications

None provided.

• Responsible Party: Philip Grant, Assistant Professor of Medicine (Infectious Diseases), Stanford University
• ClinicalTrials.gov Identifier: NCT02134184
• Other Study ID Numbers: SU-25199; 1U19AI090019-01
• First Posted: May 9, 2014
• Last Update Posted: Oct 18, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Infections; Communicable Diseases; Influenza, Human; Cytomegalovirus Infections; Vaccines

Study Results

Participant Flow

Arm/Group Title	CMV Negative Group	CMV Positive Group	Recent CMV Converters
Arm/Group Description	Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50 This vaccine is given intramuscularly	Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50 This vaccine is given intramuscularly	Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50 This vaccine is given intramuscularly Recent CMV Conversion is defined as: Donor has donated at least once within the "recent" timeframe (past three years) AND donor's most recent two donations tested CMV antibody positive AND donor had at least two CMV negative donations in the past
Period Title: Overall Study
STARTED	33	37	8
COMPLETED	33	37	8
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	CMV Negative Group	CMV Positive Group	Recent CMV Converters	Total
Arm/Group Description	Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50 Fluzone® 2012-2013 Formula: This vaccine is given intramuscularly	Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50 Fluzone® 2012-2013 Formula: This vaccine is given intramuscularly	Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50 Fluzone® 2012-2013 Formula: This vaccine is given intramuscularly	Total of all reporting groups
Overall Participants	33	37	8	78
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	12 36.4%	16 43.2%	1 12.5%	29 37.2%
>=65 years	21 63.6%	21 56.8%	7 87.5%	49 62.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.96 (4.52)	67.46 (5.26)	66.75 (3.53)	67.21 (4.80)
Sex: Female, Male (Count of Participants)
Female	10 30.3%	20 54.1%	7 87.5%	37 47.4%
Male	23 69.7%	17 45.9%	1 12.5%	41 52.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 2.7%	0 0%	1 1.3%
Not Hispanic or Latino	33 100%	36 97.3%	8 100%	77 98.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 3%	1 2.7%	0 0%	2 2.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	31 93.9%	36 97.3%	8 100%	75 96.2%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 3%	0 0%	0 0%	1 1.3%
Region of Enrollment (Count of Participants)
United States	33 100%	37 100%	8 100%	78 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants From Each Arm Who Received Influenza Vaccine
Time Frame	Day 0 to Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CMV Negative Group	CMV Positive Group	Recent CMV Converters
Arm/Group Description	Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50 This vaccine is given intramuscularly	Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50 This vaccine is given intramuscularly	Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50 This vaccine is given intramuscularly
Measure Participants	33	37	8
Count of Participants [Participants]	33 100%	37 100%	8 100%

2. Secondary Outcome

Title	Number of Participants With Related Adverse Events
Time Frame	Day 0 to Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CMV Negative Group	CMV Positive Group	Recent CMV Converters
Arm/Group Description	Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50 This vaccine is given intramuscularly	Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50 This vaccine is given intramuscularly	Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50 This vaccine is given intramuscularly
Measure Participants	33	37	8
Count of Participants [Participants]	0 0%	0 0%	0 0%

3. Other Pre-specified Outcome

Title	To Compare the T- and B-cell Response to Licensed IM TIV in Elderly Individuals Dependent on the Presence and Duration of CMV Infection by Analyses of Vaccine-induced Plasmablasts, Antibodies and Antigen-specific T Cells
Time Frame	Day 0 to Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Day 0 to Day 28 of study participation
Adverse Event Reporting Description	Clinical Assessment performed at each visit
Arm/Group Title	CMV Negative Group		CMV Positive Group		Recent CMV Converters
Arm/Group Description	Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50 This vaccine is given intramuscularly		Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50 This vaccine is given intramuscularly		Participants will receive Fluzone® 2012-2013 Formula NDC No 498281-012-50 This vaccine is given intramuscularly
All Cause Mortality
	CMV Negative Group		CMV Positive Group		Recent CMV Converters
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	CMV Negative Group		CMV Positive Group		Recent CMV Converters
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/37 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	CMV Negative Group		CMV Positive Group		Recent CMV Converters
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/33 (3%)		0/37 (0%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/33 (3%)	1	0/37 (0%)	0	0/8 (0%)	0

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.