Impact of Metabolic Syndrome on Flu Vaccine Efficacy

• Sponsor: Rockefeller University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02653495
• Collaborator: (none)
• Enrollment: 17
• Location: 1
• Arms: 2
• Duration (Months): 14
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

Metabolic syndrome (MetS) is a cluster of metabolic conditions associated with obesity that predispose individuals to coronary heart diseases and diabetes but obesity has been shown to increase the risks of other diseases like cancer and asthma. Studies have also shown that obesity increases the risk of severe influenza infection and associated death and reduces the efficacy of influenza vaccine in the obese population but yet, the molecular mechanisms have not been described. The investigators are thus hypothesizing that differences in the innate immune responses between individual with or without metabolic syndrome impact viral infection and vaccine outcome. The investigators will perform seasonal influenza vaccination in people with or without metabolic syndrome to determine if the late adaptive response assessed by antibodies titers is different between the two groups and correlates with the early immune response assessed by gene expression profile in whole blood cells. The project proposed by the investigators will contribute to a better understanding of the inflammatory phenotype associated with metabolic syndrome and establish for the first time if it affects the immune protection against infectious diseases and particularly against influenza virus infection. The results will be important to determine if the population affected by metabolic syndrome should receive anti-influenza treatment in priority in the context of a severe influenza epidemic.

Condition or Disease	Intervention/Treatment	Phase
Immune Deficiency; Metabolic Syndrome	Biological: Influenza vaccine	N/A

Detailed Description

The development of industrialization with increased food consumption and sedentarity has given rise to an obesity pandemic, which affects up to 30% of the population in countries like US, these populations being at greater risk for cardiovascular diseases, and diabetes. More than obesity per se, visceral obesity is associated with metabolic diseases that cluster together and clinically defined metabolic syndrome. MetS comprises individuals with at least three of the 5 of the following factors: abdominal obesity, high blood triglycerides, low HDL ("good cholesterol"), high blood pressure and elevated fasting glucose. Metabolic syndrome is associated with a low-grade inflammation characterized by an infiltration of immune cells particularly in the adipose tissue, the liver and the pancreas that is thought to be responsible for the induction of insulin resistance. It is thought that obesity predisposes to other diseases such as cancer, asthma but only little attention has been given to infectious diseases. Studies have shown that obesity increases the risk of severe influenza infection and associated death and reduces the efficacy of influenza vaccine in the obese population but yet, the molecular mechanisms have not been described. Immune dysfunctions associated with obesity are suspected to play a major role but obesity is often associated with respiratory disorders that could directly explain the increased susceptibility to influenza infection. Also, metabolically healthy obesity is less associated with inflammation. Therefore, the investigators would like to focus particularly on metabolic syndrome, and determine how it influences immune response to viruses.

The investigators are thus hypothesizing that differences in the innate immune responses between individual with or without metabolic syndrome impact viral infection and vaccine outcome. Recent studies involving complex biological analysis and computational modeling have shown that the ability of an individual to positively respond to influenza vaccine can be molecularly predicted by looking at markers in the blood cells. The investigators will perform seasonal influenza vaccination in people with or without metabolic syndrome to determine if the late adaptive response assessed by antibodies titers is different between the two groups and correlates with the early immune response assessed by gene expression profile in whole blood cells.

Healthy nutritional habits along with increased physical activities should be best at preventing the development of metabolic syndrome but socio-economical issues are slowing the implementation of these changes. Therefore, as metabolic syndrome is raising public health concerns, it is important to understand why the metabolic syndrome affects susceptibility to diseases.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Impact of Metabolic Syndrome on Flu Vaccine Efficacy
• Study Start Date: Jan 1, 2016
• Actual Primary Completion Date: Mar 1, 2017
• Actual Study Completion Date: Mar 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Influenza vaccine in metabolic syndrome Influenza vaccine	Biological: Influenza vaccine; Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3
Experimental: Influenza vaccine in healthy controls Influenza vaccine	Biological: Influenza vaccine; Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3

Outcome Measures

Primary Outcome Measures

1. Antibody Response D28 [28 days after vaccination compare to baseline (screening visit 1) pre-vaccination]

   Measured by hemagglutination inhibition assay

Secondary Outcome Measures

1. Gene Expression Profiling D1 [1 day post-vaccination compare to baseline (gene expression screening visit #1 and study visit #1 D0 of vaccination)]

   Analyze by RNA-seq

2. Gene Expression Profiling D28 [28 days post-vaccination compare to baseline (gene expression screening visit #1 and study visit #1 D0 of vaccination)]

   Analyze by RNA-seq

3. Gene Expression Profiling D90 [90 days post-vaccination compare to baseline (gene expression screening visit #1 and study visit #1 D0 of vaccination)]

   Analyze by RNA-seq

4. Antibody Response D90 [90 days after vaccination compare to day 28]

   Measured by hemagglutination inhibition assay

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion criteria for the METABOLIC SYNDROME COHORT( Participants must have 3 or more of the following 5 risk factors):

• Abdominal Obesity, given as a waist circumference: Men >102 cm (>40 in) Women > 88 cm (>35 in)

• Triglycerides >150 mg/dl

• HDL Cholesterol: Men < 40 mg/dl Women < 50 mg/dl

• Blood Pressure >130/ >85 mm Hg - or controlled on antihypertensive medication

• Fasting Glucose > 100 mg/dl

Inclusion criteria for the HEALTHY CONTROLS (Participants must have all of the requirements below) :

• body mass index 18.5 - 25 kg/m2

• HDL female > 50 mg/dL, male > 40 mg/dL

• fasting glucose < 100 mg/dL

• triglycerides <150 mg/dL,

• waist circumference of a female < 88 cm, male < 102 cm)

• • Blood pressure < or = to 120/80 (based on an average of 3 readings taken 5 minutes apart after the consent form has been signed)

Exclusion criteria :

• Currently undergoing treatment for the metabolic syndrome

• The average of 2 BP readings > 150/90 (based on 2 B/Ps taken at screening visit 1).

• Hepatitis A, B and C

• NSAIDs and/or Aspirin ingestion within the last 14 days

• Self-reported history of any active autoimmune diseases

• Self-reported ingestion of statins within the last 3 months

• Self-reported antibiotic use within the last 3 months

• Anti-inflammatory drugs including biologics and corticosteroids within last 3 months( nasal spray and topical applications are OK)or Omega 3 Fatty Acids.

• Self-reported hx of cancer treatment within the last year

• Allergy to eggs

• History of Guillain-Barre syndrome

• Pregnant ( determined by point of care testing at screening visit 1).

• HIV positive

• Self-reported history of flu vaccination within the past 3 months.

• Any self-reported infection in the week of the visit except the first two visits (Screening visit 1 and Screening visit 2) and the last visit (Study visit #5) that could be rescheduled.

• Any medical, psychological or social condition that, in the opinion of the Investigator, would jeopardize the health or well-being of the participant during any study procedures or the integrity of the data.

Study Population Description The population from which the groups will be selected are resident of New York City.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rockefeller University	New York	New York	United States	10065

Sponsors and Collaborators

• Rockefeller University

Investigators

• Principal Investigator: Ursula Andreo, PhD, The Rockefeller University Center for Clinical and Translational

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 7, 2017

More Information

Publications

None provided.

• Responsible Party: Rockefeller University
• ClinicalTrials.gov Identifier: NCT02653495
• Other Study ID Numbers: UAN-0891
• First Posted: Jan 12, 2016
• Last Update Posted: Sep 28, 2017
• Last Verified: Sep 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Metabolic Syndrome; Immunologic Deficiency Syndromes; Syndrome

Study Results

Participant Flow

Recruitment Details	Advertising and Research Volunteer Repository Database
Pre-assignment Detail	Pre-screening took place along with a two-step screening visit for eligibility criteria. Those not meeting eligibility would screen out: 86 prescreened, 28 initial contact for screening.

Arm/Group Title	Influenza Vaccine in Metabolic Syndrome	Influenza Vaccine in Healthy Controls
Arm/Group Description	Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3	Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3
Period Title: Overall Study
STARTED	15	2
COMPLETED	3	2
NOT COMPLETED	12	0

Baseline Characteristics

Arm/Group Title	Influenza Vaccine in Metabolic Syndrome	Influenza Vaccine in Healthy Controls	Total
Arm/Group Description	Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3	Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3	Total of all reporting groups
Overall Participants	3	2	5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	2 100%	5 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 33.3%	1 50%	2 40%
Male	2 66.7%	1 50%	3 60%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%	2 100%	5 100%

Outcome Measures

1. Primary Outcome

Title	Antibody Response D28
Description	Measured by hemagglutination inhibition assay
Time Frame	28 days after vaccination compare to baseline (screening visit 1) pre-vaccination

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Influenza Vaccine in Metabolic Syndrome	Influenza Vaccine in Healthy Controls
Arm/Group Description	Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3	Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3
Measure Participants	0	0

2. Secondary Outcome

Title	Gene Expression Profiling D1
Description	Analyze by RNA-seq
Time Frame	1 day post-vaccination compare to baseline (gene expression screening visit #1 and study visit #1 D0 of vaccination)

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Influenza Vaccine in Metabolic Syndrome	Influenza Vaccine in Healthy Controls
Arm/Group Description	Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3	Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3
Measure Participants	0	0

3. Secondary Outcome

Title	Gene Expression Profiling D28
Description	Analyze by RNA-seq
Time Frame	28 days post-vaccination compare to baseline (gene expression screening visit #1 and study visit #1 D0 of vaccination)

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Influenza Vaccine in Metabolic Syndrome	Influenza Vaccine in Healthy Controls
Arm/Group Description	Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3	Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3
Measure Participants	0	0

4. Secondary Outcome

Title	Gene Expression Profiling D90
Description	Analyze by RNA-seq
Time Frame	90 days post-vaccination compare to baseline (gene expression screening visit #1 and study visit #1 D0 of vaccination)

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Influenza Vaccine in Metabolic Syndrome	Influenza Vaccine in Healthy Controls
Arm/Group Description	Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3	Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3
Measure Participants	0	0

5. Secondary Outcome

Title	Antibody Response D90
Description	Measured by hemagglutination inhibition assay
Time Frame	90 days after vaccination compare to day 28

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Influenza Vaccine in Metabolic Syndrome	Influenza Vaccine in Healthy Controls
Arm/Group Description	Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3	Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3
Measure Participants	0	0

Adverse Events

Time Frame	Adverse event information collected from time of enrollment through completion of study visits, 3 months.
Arm/Group Title	Influenza Vaccine in Metabolic Syndrome		Influenza Vaccine in Healthy Controls
Arm/Group Description	Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3		Influenza vaccine Influenza vaccine: Influenza vaccine administered intramuscularly (IM), 1 time only, on visit 3
All Cause Mortality
	Influenza Vaccine in Metabolic Syndrome		Influenza Vaccine in Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)
Serious Adverse Events
	Influenza Vaccine in Metabolic Syndrome		Influenza Vaccine in Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Influenza Vaccine in Metabolic Syndrome		Influenza Vaccine in Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		1/2 (50%)
Gastrointestinal disorders
gastrointestinal disorders: dyspepsia	0/3 (0%)	0	1/2 (50%)	1
gastrointestinal disorders: diarrhea	1/3 (33.3%)	1	0/2 (0%)	0
Respiratory, thoracic and mediastinal disorders
Upper Respiratory	1/3 (33.3%)	1	0/2 (0%)	0
Skin and subcutaneous tissue disorders
infections and infestations: upper respiratory infection: skin infection	1/3 (33.3%)	1	0/2 (0%)	0

Limitations/Caveats

Inclusion Criteria hard to meet among population: many individuals do not self-identify as having metabolic syndrome, participants must have untreated metabolic syndrome. Challenges led to early termination with sample size not being attainable.

More Information

Certain Agreements

All Principal Investigators ARE 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.