search
Back to results

Influenza Vaccine as a Novel Experimental Model of the Behavioral Immune Response in Depression

Primary Purpose

Depression, Healthy

Status
Unknown status
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Influenza Vaccine
Sponsored by
University of Texas at Austin
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Depression focused on measuring depression, Major Depressive Disorder, depressive

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Inclusion Criteria for all subjects

  • Adults age 18-60
  • Able to provide written informed consent directly, without use of a proxy
  • Able to speak and write in English sufficiently to undergo consent and to complete self reports

Inclusion Criteria for depressed subjects

  • Currently meets criteria for a Depressive Episode and a diagnosis of MDD according Mini International Neuropsychiatric Interview (MINI)
  • Depressive severity of ≥ 12 on the Quick Inventory of Depression Symptomatology, Clinician Rated (QIDS-C), corresponding to more than mild depression severity, but <21, indicating not severe

Inclusion Criteria for healthy Subjects

  • No lifetime Axis I diagnosis on the MINI
  • QIDS-SR score <6 indicating no depression
  • CRP at screening of <1mg/L.

Exclusion Criteria:

Exclusion Criteria for all subjects

  • Active, unstable, or serious medical illness (e.g. requiring urgent out-patient or higher level of care) as determined by history and lab examination at screening. For example, subjects with untreated cardiovascular disease (blood pressure above 140/80 on repeated measurements, history of cardiac event without medical follow up) or untreated diabetes (based on symptoms and elevated fasting blood sugar at screening) will be excluded.
  • Taking medications that have a significant effect on the immune system. This includes daily Non-steroidal Anti-inflammatory medications (NSAIDs). As needed NSAIDs will not be exclusionary but subjects will be asked to refrain from NSAID usage for 48 hours prior to the vaccination visit and through the day 3 visit.
  • Has received the influenza vaccine for the current season or within the last 12 months
  • Infection with fever or otherwise clinically significant in the last two weeks. Subjects with elevated white blood cell count at screening will also be excluded.
  • Current and within the last 3 months meeting criteria for tobacco use disorder.
  • Previous severe adverse event associated with IIV
  • History of allergy to any component of the IIV
  • History of Guillain-Barre Syndrome
  • Pregnancy
  • Otherwise judged unable to comply with study procedures or unsafe to participate by study clinician

Exclusion Criteria for Depressed Subjects

  • Life-time history of mania, hypomania, or psychosis on the MINI
  • Meets or has met criteria for substance abuse or dependence in the last 6 months (3 months for nicotine)
  • Meets or has met criteria for any eating disorder in the last 6 months
  • Baseline suicidal ideation above "passive" defined as thoughts of death or dying (e.g. wish for natural death) without thoughts of active methods (e.g. overdose) or intent to die, as determined using the Concise Health Risk Tracking Scale (CHRT) (assessment interval "the last week") and clinician interview.

No Exclusion Criteria for Healthy Subjects

Sites / Locations

  • Marisa ToupsRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Depression Subjects: Influenza Vaccine

Healthy Subjects: Influenza Vaccine

Arm Description

Subjects will receive a quadrivalent inactivated influenza vaccine, for the appropriate season/year of enrollment. The vaccine will be administered by the PI or similarly trained clinician, into the deltoid muscle as directed

Subjects will receive a quadrivalent inactivated influenza vaccine, for the appropriate season/year of enrollment. The vaccine will be administered by the PI or similarly trained clinician, into the deltoid muscle as directed

Outcomes

Primary Outcome Measures

Positive and Negative Affect Schedules Score
We will compute change in scores on the PANAS-x subscales between baseline and day 1. Self reported assessment that contains both positive and negative words and phrases that describe different feelings and emotions. Subjects read each item and mark the appropriate answer for how they feel right now as they fill out the form. Possible answers and the associated score are: (1) Not at all, (2) A little, (3) Moderately, (4) Quite a bit, (5) Extremely. To rate, responses to items in each scale are summed. The scales in the PANAS are listed below with the number of items in that scale in parentheses followed by the total range of the scale. General Dimensions Negative Affect (10) 10-50 General Dimensions of Positive Affect (10) 10-50 Negative Emotion Fear (6) 6-30 Hostility (6): 6-30 Guilt (6): 6-30 Sadness (5) 5- 25 Positive Emotion Joviality (8) 8-40 Self-Assurance (6) 6-30 Attentiveness (4) 4-20 Other Affective States Shyness (4) 4-20 Fatigue (4) 4-20 Serenity (3) 3-15

Secondary Outcome Measures

Change in Cytokine Concentration (pg/mL)
We will compute differences in cytokine (IFN- α, IFN-y, IL-6, IL1-β and TNF-α) values for each subject between baseline and day 1 and days 1 and 3. Using OLS regression we will compute regressions between hypothesis appropriate time points using baseline CRP, QIDS, PANAS score and BMI as covariates.
Difference in PGE4/LipoxinA4 Ratio
After determining the difference in the PGE4/LipoxinA4 ratio between days 1 and 3, we will perform a similar regression.
Tryptophan Metabolites
We will calculate difference between baseline and day 1 in the KYN/TRP and KYNA/QUIN ratios and us them in regression models as above, correcting for two tests.
HPA Axis
To test the hypothesis that ACTH/cortisol affects peak inflammatory cytokine levels in MDD, we will use similar OLS regression models including HPA-axis response as a covariate and examining its interaction with cytokines as the dependent variables.

Full Information

First Posted
November 14, 2018
Last Updated
June 25, 2019
Sponsor
University of Texas at Austin
search

1. Study Identification

Unique Protocol Identification Number
NCT03756246
Brief Title
Influenza Vaccine as a Novel Experimental Model of the Behavioral Immune Response in Depression
Official Title
Influenza Vaccine as a Novel Experimental Model of the Behavioral Immune Response in Depression
Study Type
Interventional

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Unknown status
Study Start Date
June 10, 2019 (Actual)
Primary Completion Date
May 2020 (Anticipated)
Study Completion Date
May 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Texas at Austin

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine differences between the immune responses in healthy and depressed people. Participants will receive the influenza vaccine and their responses will be monitored. This study will recruit 15 healthy and 60 depressed participants.
Detailed Description
The purpose of this study is to determine differences between the immune responses in healthy and depressed people. Specifically subjects are provided a mild immune stimulus, an influenza vaccine, and their responses are monitored. The goals are to determine whether patients with depression experience a temporary worsening of mood in response to the stimulus and whether this is associated with measurable differences in the cytokine response to the vaccine. Additionally, patients with depression may be less likely to mount a successful antibody response to vaccination as healthy people based on circumstantial evidence, and this study will assess whether this the case. This study aims to recruit a sample of 15 healthy and 60 depressed participants. The 15 healthy participants will be age and gender matched to the first 15 depressed participants recruited. Three more sets of age and gender matched depressed subjects will be recruited. This will result in 15 sets of "quintuplets" (4 depressed and one healthy), that are matched by age and gender. The study consists of four visits. The first visit is the baseline assessment where participants will receive the influenza vaccine. Participants will then return 1, 3 and 28 days after receiving the vaccine to assess their responses.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression, Healthy
Keywords
depression, Major Depressive Disorder, depressive

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Both healthy and depressed arms will receive the influenza vaccine.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Depression Subjects: Influenza Vaccine
Arm Type
Experimental
Arm Description
Subjects will receive a quadrivalent inactivated influenza vaccine, for the appropriate season/year of enrollment. The vaccine will be administered by the PI or similarly trained clinician, into the deltoid muscle as directed
Arm Title
Healthy Subjects: Influenza Vaccine
Arm Type
Active Comparator
Arm Description
Subjects will receive a quadrivalent inactivated influenza vaccine, for the appropriate season/year of enrollment. The vaccine will be administered by the PI or similarly trained clinician, into the deltoid muscle as directed
Intervention Type
Biological
Intervention Name(s)
Influenza Vaccine
Other Intervention Name(s)
flu shot, flu vaccine
Intervention Description
The appropriate quadrivalent influenza vaccine for the give year will be given to subjects.
Primary Outcome Measure Information:
Title
Positive and Negative Affect Schedules Score
Description
We will compute change in scores on the PANAS-x subscales between baseline and day 1. Self reported assessment that contains both positive and negative words and phrases that describe different feelings and emotions. Subjects read each item and mark the appropriate answer for how they feel right now as they fill out the form. Possible answers and the associated score are: (1) Not at all, (2) A little, (3) Moderately, (4) Quite a bit, (5) Extremely. To rate, responses to items in each scale are summed. The scales in the PANAS are listed below with the number of items in that scale in parentheses followed by the total range of the scale. General Dimensions Negative Affect (10) 10-50 General Dimensions of Positive Affect (10) 10-50 Negative Emotion Fear (6) 6-30 Hostility (6): 6-30 Guilt (6): 6-30 Sadness (5) 5- 25 Positive Emotion Joviality (8) 8-40 Self-Assurance (6) 6-30 Attentiveness (4) 4-20 Other Affective States Shyness (4) 4-20 Fatigue (4) 4-20 Serenity (3) 3-15
Time Frame
1 Day
Secondary Outcome Measure Information:
Title
Change in Cytokine Concentration (pg/mL)
Description
We will compute differences in cytokine (IFN- α, IFN-y, IL-6, IL1-β and TNF-α) values for each subject between baseline and day 1 and days 1 and 3. Using OLS regression we will compute regressions between hypothesis appropriate time points using baseline CRP, QIDS, PANAS score and BMI as covariates.
Time Frame
3 Days
Title
Difference in PGE4/LipoxinA4 Ratio
Description
After determining the difference in the PGE4/LipoxinA4 ratio between days 1 and 3, we will perform a similar regression.
Time Frame
3 Days
Title
Tryptophan Metabolites
Description
We will calculate difference between baseline and day 1 in the KYN/TRP and KYNA/QUIN ratios and us them in regression models as above, correcting for two tests.
Time Frame
1 Day
Title
HPA Axis
Description
To test the hypothesis that ACTH/cortisol affects peak inflammatory cytokine levels in MDD, we will use similar OLS regression models including HPA-axis response as a covariate and examining its interaction with cytokines as the dependent variables.
Time Frame
3 Days
Other Pre-specified Outcome Measures:
Title
Fold Change
Description
: Fold change from pre- to 28 days post-vaccine will be calculated for each of the three influenza strains targeted by the vaccine. Fold change > 4 to any one of the three strains will be considered "success." Proportion of successful vaccination will be compared between HC and MDD using a linear model adjusted for age and pre-vaccination titer, which have been shown to affect antibody response.
Time Frame
28 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Inclusion Criteria for all subjects Adults age 18-60 Able to provide written informed consent directly, without use of a proxy Able to speak and write in English sufficiently to undergo consent and to complete self reports Inclusion Criteria for depressed subjects Currently meets criteria for a Depressive Episode and a diagnosis of MDD according Mini International Neuropsychiatric Interview (MINI) Depressive severity of ≥ 12 on the Quick Inventory of Depression Symptomatology, Clinician Rated (QIDS-C), corresponding to more than mild depression severity, but <21, indicating not severe Inclusion Criteria for healthy Subjects No lifetime Axis I diagnosis on the MINI QIDS-SR score <6 indicating no depression CRP at screening of <1mg/L. Exclusion Criteria: Exclusion Criteria for all subjects Active, unstable, or serious medical illness (e.g. requiring urgent out-patient or higher level of care) as determined by history and lab examination at screening. For example, subjects with untreated cardiovascular disease (blood pressure above 140/80 on repeated measurements, history of cardiac event without medical follow up) or untreated diabetes (based on symptoms and elevated fasting blood sugar at screening) will be excluded. Taking medications that have a significant effect on the immune system. This includes daily Non-steroidal Anti-inflammatory medications (NSAIDs). As needed NSAIDs will not be exclusionary but subjects will be asked to refrain from NSAID usage for 48 hours prior to the vaccination visit and through the day 3 visit. Has received the influenza vaccine for the current season or within the last 12 months Infection with fever or otherwise clinically significant in the last two weeks. Subjects with elevated white blood cell count at screening will also be excluded. Current and within the last 3 months meeting criteria for tobacco use disorder. Previous severe adverse event associated with IIV History of allergy to any component of the IIV History of Guillain-Barre Syndrome Pregnancy Otherwise judged unable to comply with study procedures or unsafe to participate by study clinician Exclusion Criteria for Depressed Subjects Life-time history of mania, hypomania, or psychosis on the MINI Meets or has met criteria for substance abuse or dependence in the last 6 months (3 months for nicotine) Meets or has met criteria for any eating disorder in the last 6 months Baseline suicidal ideation above "passive" defined as thoughts of death or dying (e.g. wish for natural death) without thoughts of active methods (e.g. overdose) or intent to die, as determined using the Concise Health Risk Tracking Scale (CHRT) (assessment interval "the last week") and clinician interview. No Exclusion Criteria for Healthy Subjects
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Project Coordinator
Phone
512-495-5595
Email
behavioral.immunology.lab@dellmed.utexas.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Maria Toups, M.D.
Phone
512-494-4672
Email
marisa.toups@austin.utexas.edu
Facility Information:
Facility Name
Marisa Toups
City
Austin
State/Province
Texas
ZIP/Postal Code
78701
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Project Coordinator
Phone
512-495-5595
Email
behavioral.immunology.lab@dellmed.utexas.edu
First Name & Middle Initial & Last Name & Degree
Alyssa Marron
Phone
512-495-5595
Email
alyssa.marron@austin.utexas.edu
First Name & Middle Initial & Last Name & Degree
Marisa Toups, MD

12. IPD Sharing Statement

Learn more about this trial

Influenza Vaccine as a Novel Experimental Model of the Behavioral Immune Response in Depression

We'll reach out to this number within 24 hrs