Systems Biological Assessment of Statin Effect on Vaccine Responses
Phase: PHASE4
Conditions: Vaccine Response
Sponsor: Emory University

 
 
 
 
 
 
 
 
Systems Biological Assessment of Statin Effect on Vaccine Responses 
STUDY00006239 
 
Date: October 11, 2023 
NCT06024096 

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PROTOCOL TITLE: Systems Biological Assessment of Statin Effect on Vaccine Responses
PRINCIPAL INVESTIGATOR:
, MD
Hope Clinic of the Emory Vaccine Center
Division of Infectious Diseases, Department of Medicine
Telephone Number 
 
Pager: 
Email: 
CO- PRINCIPAL INVESTIGATOR
, MD
Department of Medicine, Emory University
, MD
Department of Medicine, Emory University
, MD
Department of Medicine, Emory University 
EXTERNAL (NON-EMORY) COLLABORATORS                                                                   
, PhD*
Department of Pathology, Stanford University
*Please note that 
 will not be engaged in human subjects research.
VERSION: 2.0
FUNDING SOURCE: Internal fund

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REVISION HISTORY
Revision #
Version 
Date
Summary of Changes
2.0
11Oct2023
- Specified that for the memory aid, participants will have 
an option between online survey or paper form
- Clarified that clinical labs will be collected at baseline for 
all participants and that these may be repeated at 
investigator discretion

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Table of Contents
1.
Study Summary....................................................................................................................4
2.
Objectives ............................................................................................................................5
3.
Background..........................................................................................................................5
4.
Study Endpoints...................................................................................................................6
5.
Study Intervention/Investigational Agent ...........................................................................6
6.
Procedures Involved ............................................................................................................7
7.
Statistical Analysis Plan........................................................................................................9
8.
Data and/or Specimen Banking .........................................................................................10
9.
Sharing of Results with Participants ..................................................................................10
10.
Study Timelines..................................................................................................................11
11.
Inclusion and Exclusion Criteria.........................................................................................11
12.
Population .........................................................................................................................12
13.
Vulnerable Populations .....................................................................................................12
14.
Local Number of Participants ............................................................................................12
15.
Recruitment Methods........................................................................................................12
16.
Withdrawal of Participants................................................................................................13
17.
Drug halting rules ..............................................................................................................13
18.
Risk to Participants ............................................................................................................14
19.
Potential Benefits to Participants......................................................................................15
20.
Compensation to Participants ...........................................................................................15
21.
Data Management and Confidentiality .............................................................................16
22.
Plans to Monitor the Data to Ensure Safety of Participants and Data Integrity................17
23.
Provisions to Protect the Privacy Interest of Participants .................................................26
24.
Economic Burden to Participants ......................................................................................26
25.
Informed Consent..............................................................................................................27
26.
Setting................................................................................................................................28
27.
Resources Available...........................................................................................................28
28.
References.........................................................................................................................28

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1. Study Summary
Project Title
Systems Biological Assessment of Statin Effect on 
Vaccine Responses.
Project Design
Longitudinal cohort study in which participants will 
receive either 8 weeks of statin therapy and a 
seasonal quadrivalent influenza vaccine (QIV) or a 
seasonal quadrivalent influenza vaccine (QIV) alone.
Immune responses in the blood will be assessed.
Primary Objective
Compare the antibody (Ab) response to QIV in statin 
recipients and non-recipients.
Secondary Objectives
Assess the safety profile of statin therapy + QIV  v/s 
QIV alone.
Exploratory Objectives

Explore the effect of statin therapy on immune 
signatures after vaccination.

Evaluate the effect of statin therapy on plasma 
cytokine responses to vaccination.
Research 
Intervention(s)/Interactions
Initiation of 8 weeks of statin therapy and 
immunization with a single dose of seasonal QIV. 
Study Population
Healthy adults (age 18 to 50 years) without history of 
statin use and without current receipt of seasonal 
influenza vaccine or recent influenza infection.
Sample Size
N=30 in the Statin + QIV arm.
N=30 in the QIV alone arm.
Study Duration for 
individual participants
8 months.
Study Specific 
Abbreviations/ Definitions 
Ab –antibody
QIV – seasonal quadrivalent influenza vaccine
Funding Source 
Hope Clinic Internal funds
2. Objectives

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Primary Objective:
Compare the antibody (Ab) response to QIV in statin recipients and non-recipients.
Secondary Objective:
Assess the safety profile of statin therapy + QIV v/s QIV alone.
Exploratory Objectives:
1. Explore the effect of statin therapy on innate immune signatures to QIV.
2. Evaluate the effect of statin therapy on plasma cytokine response to QIV.
 
3. Background
Statins are widely used for their lipid-lowering and cardiovascular protective effects1. Additional 
research has shown that statins can be anti-inflammatory, and play a part in modulating the 
immune system2-4. These effects are called into action in events such as pneumonia5, 
influenza6,7, and sepsis8. 
Statins decrease cholesterol synthesis by inhibiting the enzyme HMG-CoA reductase. This 
results in the activation of the SREBP pathway which promotes cholesterol uptake and 
synthesis9. One study investigated the role of SREBP signaling in B cell responses using a mouse 
model. It was demonstrated that SREBP inhibition decreased gene activation involved in lipid 
metabolism and fatty acid synthesis which is essential for antibody production. This resulted in 
a decrease in B cell differentiation to plasma cells and a deficiency in production of high-affinity 
antibodies10.
Studies evaluating the effects of statins on the immune system’s response to the influenza 
vaccine have provided mixed results. Many studies have shown that chronic statin therapy 
negatively influences the influenza vaccine’s efficacy, with titer levels markedly lower than in 
statin nonusers11. Other researchers showed that statin therapy may only partly alter the 
immune response to the influenza vaccine against some strains, while the protection against 
other strains remained intact12. Another study involving a large population of statin users and 
statin nonusers, found that statin users had lower influenza vaccine effectiveness against acute 
respiratory illness than nonusers13. However, other retrospective cohort studies found that the 
difference in vaccine effectiveness between statin users and nonusers was not significant and 
did not translate into a difference in the clinical course of the disease14,15.
One study compared the gut microbiota in statin users and statin non users. The results proved 
that statin therapy significantly lowered the prevalence of gut microbiota dysbiosis. The 
reshaping of the microbiota to limit potentially harmful bacteria and increase beneficial 
bacteria, as well as the increase in gut microbiota diversity may contribute to a better vaccine 
response16. In fact, Oh et al. conducted a study on influenza vaccine which showcased the role 
of the microbiota in boosting vaccine immunity. The findings prove that the microbiome is one 
of the factors contributing to the effectiveness of vaccines17.

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Systems vaccinology involves applying systems biology principles to the field of vaccinology 
with a view to predict vaccine efficacy. Our objective is to identify molecular signatures or 
patterns of gene expression that are altered after the use of chronic statin therapy and analyze 
the innate and adaptive immune mechanisms responsible for this effect18. 
4. Study Endpoints
Primary Endpoint:
Magnitude of antibody responses to QIV at 29 days after vaccination in each study group.
Secondary Endpoint:
Frequency and severity of adverse events until Day 29 and serious adverse events until D181   
after vaccination in each study group.
Exploratory Endpoints:
1. Identification of innate immune signatures until 7 days after vaccination that predict the 
magnitude and durability of Ab response Days 29, 91 and 181after vaccination in each study 
group. 
2. Plasma cytokine response until 7 days after vaccination in each study group.
5. Study Intervention/Investigational Agent 
5.1 Description
Atorvastatin therapy
Atorvastatin is a lipid-lowering agent of the statin family that functions by blocking a rate-
limiting enzyme, HMG-CoA reductase, in the lipid metabolism. This agent is commonly used for 
primary and secondary prevention of dyslipidemia. Participants will be asked to take 
Atorvastatin 80 mg daily at night, for 4 weeks prior to the vaccination and continue the statin 
therapy for 4 weeks after vaccination. 
The 80mg dose of atorvastatin allows for evaluation of the immunologic effects of statin 
medication with a short duration of therapy prior to vaccination. Studies have shown that 80mg 
of atorvastatin for 1 month affects inflammatory responses while lower doses of statin for 
longer periods may not. The 80mg dose reduced inflammation related to including NF-kB while 
other studies looking at lower doses of statin for 3 months did not find a difference in NF-kB19. 
Observational studies have investigated the dose-response question for statin therapy and 
vaccine effect but they either had insufficient sample size for that question20 or there was a 
trend toward lower vaccine efficacy with higher dose statin, though this was not statistically 
significant21.

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Quadrivalent seasonal influenza vaccine
The FDA-approved quadrivalent seasonal influenza vaccine contains four distinct strains: two 
influenza A viruses and two influenza B viruses. The approved seasonal QIV will be purchased 
from the manufacturer to be given for each season of influenza. 
5.2 Drug Handling
Atorvastatin and QIV will be stored at the Emory Investigational Drug Service (IDS) per the 
manufacturer’s instructions. It will be prepared by an IDS pharmacist on site at the  Hope Clinic 
satellite IDS. Logs of receipt, temperature, maintenance, and disposal will be maintained in the 
study file. 
The Atorvastatin therapy will be dispensed by a study coordinator, nurse or provider at the 
Hope Clinic with clear instructions on how and when to take the pills. Participants will be 
instructed to contact the clinic staff immediately if they develop  concerning symptoms 
following the administration of the drug. 
QIV will be administered by a study nurse or provider at the Hope Clinic as a single 0.5mL 
intramuscular injection in the deltoid muscle.
5.3 Accountability Procedures for Study Products
The IDS pharmacist will maintain accurate drug accountability logs which will be kept at the IDS 
pharmacy until the completion of the study. Upon completion of the study, a final drug 
accountability will be done. Following the completion of the drug accountability, the original 
copies of the logs will be maintained. When the vaccine is administered to a participant, the 
date, time and location of the injection will be recorded in the participant’s study source 
documentation records.
6. Procedures Involved
For a schedule of procedures, see Appendix A.
6.1 Screening and Consenting (D-60 to D-32)
6.1.1 Potential participants interested in the study study will respond to study ads. Recruiters 
from the Hope Clinic will then contact them for a telephone screening, during which the 
research study will be explained in lay terms and eligibility criteria will be reviewed. If all 
eligibility criteria are met and the participant remains interested, an in-person screening 
appointment will be scheduled. Prior participants in other studies conducted at the Hope Clinic, 
and who had indicated their willingness to participate in other studies may also be contacted 
for a telephone screening visit. 

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6.1.2 At the in-person screening appointment , study staff will review the informed consent 
form with the participant and will answer all questions related to the study. Once the 
participant signs the informed consent, they will be assigned a unique study participation 
number. The following procedures will be performed:
-
Recording of demographic information and review of medical history including recent 
influenza infection, including current medication use (medications that may interact 
with Atorvastatin) and vaccination history (previous receipt of influenza vaccines).
-
Vital signs and targeted physical exam as indicated based on review of participant health 
status.
-
A urine pregnancy test will be performed if the participant is a woman of child-bearing 
potential.
-
Blood sample collection for baseline immunological assays and baseline clinical labs. 
Clinical labs may be repeated at investigator discretion.  
6.1.3
Participants who remain eligible for the study will be randomized to either Statin 
therapy + QIV arm or QIV alone arm. Participants randomized to the Statin therapy+ 
QIV arm will receive the Atorvastatin pills with clear instructions on how to use them 
in a separate visit.
6.1.4 Clinical staff wil provide participants with a stool collection kit along with an information 
sheet explaining how the stool collection is done. The steps will be explained to the participant 
who will be asked to provide a stool sample on D-31, D1, and D29. 
6.2 Initiation of Statin therapy (D-31 to D-29)
Participants randomized to the Statin + QIV arm will be asked to come back to the Hope Clinic 
for an extra visit one month prior to date of vaccination. The following procedures will be 
performed: 

Review of interim medical history for any updates or changes. 

Review of concomitant medications for any updates or changes. 

Recording of vital signs and targeted physical exam if indicated. 

Blood sample collection. 

Stool sample collection.

Re-verification of eligibility criteria. 

Completion of prescription form by licenced provider and dispension of Atorvastatin 
80mg by the pharmacy at the clinic. 

Distribution of the drug to participant by study coordinator or nurse or provider with 
clear instructions on modalities of administration of the drug and common side-effects.
6.3 Phone call (15 days after initiation of Statin therapy)

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Fifteen days after initiation of Atorvastatin therapy, the study staff will call participant to assess 
participant compliance and any complications due to the drug. If needed, the participant will be 
asked to come to clinic for further assessment. The call will last approximately 15 minutes.
6.4 Vaccination Visit (D1)
The following actions will be performed on the day of vaccination:
-
Review of inclusion and exclusion criteria to confirm eligibility. 
-
Review of medical history, concomitant medications and vaccinations.
-
Collection of vital signs. 
-
Completion of a targeted physical exam if needed.
-
For participants of child-bearing potential, a negative urine pregnancy test is required.
-
For the statin therapy group, participant compliance to the drug will be assessed. 
-
Blood samples for immunologic assays will be collected prior to vaccination
-
Stool sample collection
-
Participants will receive the CDC influenza vaccine information sheet and review it prior 
to vaccination.
-
Participants will then receive QIV via the intramuscular route, administered by a clinical 
research nurse or provider. 
-
Participants will be observed for a minimum of 15 minutes for any immediate 
hypersensitivity reactions.
-
Participants will be asked to fill a memory aid for 7 days after vaccination. Participants 
will have the option of an online survey or paper memory aid. 
The visit will last approximately 60 minutes.
6.5 Follow-up Visits (D2, D4, D8, D15, D29, D91, D181)
All participants will return for follow-up visits following vaccination. During these visits, study 
personnel will:
-
Review the participant’s current health status.
-
Note any changes in health history since the screening visit, including current 
medication use and vaccination history.
-
Collect blood samples for immunological assays.
-
Review memory aid until Day 8. 
-
Record adverse events until Day 29. 
-
Record serious adverse events until D181.
The visit will last approximately 30 minutes.
Participants will be asked to provide a stool sample on D29 in addition to the above described 
procedures.
7. Statistical Analysis Plan

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This is an exploratory, non-placebo controlled analysis of immune responses obtained
from blood samples. This will provide us with descriptive data to analyze immune responses.
Analysis of Primary Endpoint: Magnitude of antibody responses to QIV at 29 days after 
vaccination in each study group.
Analysis of Secondary Endpoint: Frequency and severity of adverse events until Day 29 and 
serious adverse events until D181 after vaccination in each study group.
Descriptive analysis, e.g. tables and histograms, will be conducted to present severity of all AEs. 
The frequency will be tabulated. Ad hoc analyses of correlations of reactogenicity events with 
innate and adaptive immune responses may be conducted. 
The study staff will aim to enroll 30 participants in each of the statin therapy+QIV and QIV alone 
arms.
8. Data and/or Specimen Banking
Particiants will be asked for permission for the principal investigator to keep any remaining
(residual) specimens derived from venous blood collection for possible use in future research 
studies, such as examining additional immunological assessments or testing for antibodies 
against other viruses or bacteria. Future use samples/specimens will not be sold or used 
directly for production of any commercial product. These samples/specimens are protocol-
required; thus, participants must agree to future use of these samples/specimens as a condition 
of their study participation.
These samples/specimens will be stored at the Hope Clinic and shipped regulary to 
 
 lab at Stanford and other collaborating labs. The de-identified (all personal 
identifying information of the participant will be removed) samples/specimens will be labeled 
and stored in freezers at -80°C or in liquid nitrogen tanks.
In keeping with NIH policy on scientific data sharing, gene expression (RNA sequencing) data 
and immunological assay results will be made publicly available through public database 
deposition and peer-reviewed publication. Participants will be fully de-identified (i.e., 
disseminated data will not contain direct identifiable information). Demographic data (e.g., age, 
race and/or ethnicity, sex/gender) associated with participants will be kept strictly separate 
from all experimental results, including gene expression data. This practice has become 
standard to protect participant privacy.
9. Sharing of Results with Participants
Laboratory results

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Immunologic assay or omicsresults will not be reported to participants as these are intended 
for research purposes only and therefore cannot be reported to patients per Clinical Laboratory 
Improvement Amendment (CLIA) regulations. 
The results from safety laboratory tests conducted prior to statin therapy can be shared with 
participants. 
Incidental findings 
Incidental findings that appear in the results of the safety labs drawn will be disclosed and 
explained to the participant by the study investigator, who will provide a referral to the 
appropriate clinical specialist and information on how to obtain health insurance to secure 
treatment if needed. The study investigator will also send a message to the participant’s 
primary care provider requesting follow-up with the participant if the participant authorizes this 
and provides relevant contact information.
10. Study Timelines
Individuals will participate in this study for a total of 8 months. Recruitment of all participants 
will require 24 months. The study and data analysis should be concluded within 48 months of 
start date. 
11. Inclusion and Exclusion Criteria
Inclusion Criteria
1. Able to understand and give informed consent.
2. Age 18-50 years.
3. Women of child bearing potential must agree to use effective birth control for the first 3 
months of the study. A negative urine pregnancy test must be documented prior to 
vaccination. 
Exclusion Criteria for All Participants
1. History of allergy or serious adverse reaction, including Guillain-Barré syndrome, to a 
vaccine or vaccine products.
2. History of a medical condition resulting in impaired immunity such as active solid 
tumors, leukemia, lymphoma, use of immunosuppressive drugs, chemotherapy or 
radiation therapy. Persons with previous skin cancers or cured non-lymphatic tumors 
are not excluded from the study.
3. History of HIV, Hepatitis B or Hepatitis C infection.
4. Chronic clinically significant medical problems that could be considered active or 
unstable (i.e diagnosed within the past 3 months or requiring a change in medication 
within the past 3 months). This is including (but not limited to):
a. Insulin dependent diabetes

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b. Severe heart disease (including arrhythmias)
c.
Severe lung disease
d. Severe liver disease
e. Severe kidney disease
f.
Severe hypertension: defined as life-threatening consequences (e.g., malignant 
hypertension, transient or permanent neurologic deficit). 
5. BMI > 30
6. Current or previous use of statins or any other lipid-lowering drug.
7. Pregnancy or breast feeding, or plans to become pregnant in the first 3 months of study 
participation.
8. History of influenza infection within the same influenza season.
9. Receipt of blood products or immune globulin product within the prior 3 months. 
10. History of excessive alcohol consumption, drug use, psychiatric conditions, social 
conditions or occupational conditions that in the opinion of the investigator would 
preclude compliance with the trial.
11. Receipt of any live vaccines 30 days before, or plans to receive any live vaccines 30 days 
after vaccination. 
12. Receipt of any inactivated vaccines 14 days before, or plans to receive any inactivated 
vaccines 14 days after vaccination.
For participants randomized to the statin therapy+QIV group:
1. Participant is currently taking any medication that has known interactions with statin 
therapy.
2. History of renal or hepatic impairment. 
3. Safety lab results showing: 
a. CPK ≥ 1.5 ULN
b. AST ≥ 1.5 ULN
c.
ALT ≥ 1.5 ULN
d. LDL ≥ 160 mg/dL
12. Population
HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of 
other biologically active substances derived from cholesterol. This may cause fetal harm when 
administered to pregnant female. Pregnant women are also excluded from the study as their 
immune responses after vaccination will differ from the general population.
13. Vulnerable Populations
No vulnerable populations will be enrolled. Specifically, pregnant persons, children, prisoners, 
and cognitively impaired persons will not be enrolled. Non-English speakers will not be 
excluded. 

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14. Local Number of Participants
We anticipate needing to enroll and screen 150 participants locally to identify 30 participants in 
the statin therapy QIV arm and 30 participants in the QIV alone arm. 
15. Recruitment Methods
15.1 Patients will be recruited following IRB approval.
15.2 Participants will be recruited from the general population of metro Atlanta with the 
methods detailed below. 
15.3 Participants may be identified and recruited from past subjects who agreed to be 
contacted for future studies or by self-referral from IRB approved advertisements from

postings of IRB-approved flyers in and around the Emory University campuses as well as 
on electronic notification boards ; posting approved flyers on Emory and partner 
institution shuttles (e.g., Georgia Tech); 

use of various social media platforms such as Facebook, Twitter, Instagram, and other 
mobile apps in compliance with Emory policy; Study staff will use the official Emory 
University Facebook account and Instagram Emory Get Involved account, where IRB 
approved social media ads will be posted. The potential volunteers fill in their contact 
information in the “lead document form” provided by Facebook by default. The form 
collects the potential participant’s basic contact information such as name, best contact 
phone number and email address etc. Facebook collects the leads and provides it to the 
recruitment staff, who save the data in a password protected database on the Emory 
Hope Clinic’s shared drive. 

listservs (such as CDC, Emory University, Emory Vaccine Center, and Vaccine Dinner 
Club), and clinical trial recruitment websites such as Research Match.org; 
listing of clinical trials on the Emory clinical trials database (clinicaltrials.emory.edu);   
contacting past participants from the HIPAA-compliant clinical trials database at the 
Hope Clinic who have agreed to be contacted for future studies; presentations by Hope 
Clinic faculty at various University and community venues; and volunteer word-of-mouth 
(direct referrals).
Study recruiters/coordinators will contact potential volunteers once identified and tell them 
about the study and see if he/she is interested. If the potential subject is interested, the 
recruiter will obtain an oral consent and prescreen them for the study using an IRB-approved 
screening checklist. Qualified subjects will be scheduled to come into the clinic and be fully 
consented and proceed with screening/enrollment.
16. Withdrawal of Participants
Participants may voluntarily withdraw their consent from all future study activities including 
follow up at any time without penalty or loss of benefits to which they are otherwise entitled. 

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Participants may be terminated from the study prior to study completion for reasons that might 
include, but are not limited to, those listed below. The investigator will inform the 
participantthat all data acquired prior to termination will be included in the study analysis 
unless participant withdraws
consent.
16.1 Participant no longer meets eligibility criteria. 
16.2 The participant is considered by the PI to be “lost to follow-up” (i.e., no further followup is 
possible because attempts to reestablish contact with the subject have failed).
16.3 The participant dies.
16.4 As deemed necessary by the PI or designee for noncompliance of any nature.
16.5 The participant becomes pregnant.
16.6 If the study is prematurely terminated by the sponsor or the investigator for any reason, 
the investigator will promptly inform the study participantsand assure appropriate follow-up, as 
necessary. The investigator will provide a detailed written explanation of the termination to the 
IRB.
Participants with early termination status (before Day 8) are replaced as needed to preserve 
adequate sample size for the primary endpoint analysis.
17. Continuation of treatment
-
Following initiation of statin therapy, participants randomized to the statin therapy+QIV 
group will: Continue receiving the study drug as planned if they experience grade 1 
diarrhea or grade 1 elevation in CPK(>ULN - 2.5 x ULN) or LFTs (>ULN - 3.0 x ULN).
-
Temporarily halt receipt of statin therapy for three to 7 days days and receive a new set 
of safety labs (CPK; LFTs) if they experience  a grade 2 elevation in CPK (>2.5 x ULN - 5 x 
ULN) or LFTs (>3.0 - 5.0 x ULN) and without alternative etiology. If afterwards the labs 
are graded 1 or within normal limits, the participant may restart the statin therapy. If 
the labs do not trend to grade 1 , the drug will be halted and the participant will be 
followed for safety and not vaccination if prior to D1. 
-
Permanently halt receipt of statin therapy if they experience a grade 3 elevation in CPK ( 
>5 x ULN - 10 x ULN) or LFTs (>5.0 - 20.0 x ULN) after starting ST.
-
The same rules apply to diarrhea and myalgias and other symptoms related to statin.
18. Risk to Participants
18.1 Risks of Investigational Products/Interventions
Atorvastatin therapy
Atorvastatin is an FDA-approved lipid lowering drug that is widely used. In some cases, this 
statin may be associated with the following risks:
-
Diarrhea, nasopharyngitis, arthralgia in 4-14%

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-
Insomnia in 3%
-
Nausea and dyspepsia in 4-6%
-
Increased transaminases in 2-3%
-
Muscle spasms, myalgia, musculoskeletal pain in 3 to 8% 
Treatment with Atorvastatin may also be rarely linked to more serious risks such as:
-
Hypersensitivity or severe allergic reaction including anaphylaxis, angioneurotic edema, 
erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis
-
Acute liver failure or decompensated cirrhosis
-
Nonserious and reversible cognitive side effects
-
Fatal and nonfatal hepatic failure
-
Increases in HbA1c and fasting serum glucose levels 
-
Myopathy and rhabdomyolysis: risk increased with renal impairment, age>65 and 
hypothyroidism
-
Increases in serum transaminases. These changes occurred following the start of statin 
therapy, were not accompanied by other symptoms, and reversible after drug 
discontinuation
-
Persistent increases to more than three times the ULN in serum transaminases have 
occurred in approximately 0.7% of patients
-
Immune-mediated necrotizing myopathy: characterized by muscle biopsy showing 
necrotizing myopathy without significant inflammation, improvement with 
immunosuppressive agents, proximal muscle weakness, and elevated serum creatine 
kinase, which persist despite discontinuation of statin treatment
A scientific statement from the American Heart Association22 supports the safety of statin 
therapy including in people at low risk for cardiovascular disease, noting the risk of statin-
induced serious muscle injury is <0.1% and risk of serious hepatotoxicity is <0.01%. Current 
product labels do not include the need for routine monitoring of liver enzymes if these are 
normal prior to initiating statin therapy. For safety, liver enzymes and creatine phosphokinase 
(CPK) will be monitored on a regular basis during the study.
Seasonal influenza vaccine
The potential harms of receiving the influenza vaccine include, but are not limited to: pain and 
redness at the injection site, muscle aches, fatigue, and headache. These reactions occur in 10-
25% of adults who receive influenza vaccine. Serious adverse reactions including anaphylaxis 
and Guillain-Barré syndrome are possible, but rare. Potential participants with a history of 
severe allergic reaction to any component of the vaccine or Guillain-Barré syndrome after 
previous influenza vaccination will not be enrolled. For further details, see the attached 
package insert.
18.2 Risks of study procedures

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Blood draws
The risks of blood sample collection include a transient feeling of discomfort and may result in a 
vasvogal reaction. This risk is controlled by having the participantlie down prior to collection, if 
needed. A bruise might form at the site of the blood draw, and this can be avoided by 
maintaining pressure to this site following the blood draw. The sites of blood draw are potential 
sites of infection, but this risk is made very unlikely by the use of sterile technique.
18.3 Risk of Concomitant Medications, Prophylactic Medications and Rescue Medications
While we do not expect to use any additional medication, in case of anaphylactic or 
hypersensitivity reactions, we have readily available epinephrine (1:1000) and 
diphenhydramine injections. The use of epinephrine injection may cause side effects such as 
high blood pressure, arrhythmia, lightheadedness, nervousness, restlessness, tremor, shortness 
of breath, and diaphoresis; however, the frequency of these side effects is not determined. 
Diphenhydramine injection may also be necessary to treat potential allergic reactions, and its 
use may cause low blood pressure, arrhythmia, confusion, dizziness, sedation, restlessness, 
diarrhea, nausea, and urinary retention, but the frequency of these side effects is also 
unknown.
When facing a medical emergency, the clinic staff will follow the institutional SOP by calling 911 
first (Hope Clinic). If needed, the participantwill be transferred to the Emory University Hospital 
or Emory Decatur Hospital Emergency Department for further care.
Participants are allowed to use acetaminophen or other symptomatic treatment if they 
experience a moderate to severe local or systemic side effect after vaccine administration. 
19. Potential Benefits to Participants
The participants will be administered the influenza vaccine that has been approved by the FDA, 
which may potentially provide them with protection against influenza viruses. The United 
States Advisory Committee on Immunization Practices (ACIP) recommends the influenza 
vaccine for individuals aged 6 months and above, as it is known to be effective in preventing 
influenza virus infection.
20. Compensation to Participants
As compensation for expenses/travel and time, participants will receive $75 for each visit that 
involves a blood draw, $100 for the statin initiation visit, and $125 for the vaccination visit. Any 
unscheduled visit will be compensated at $50. Phone visits are compensated $20 per call. 
Compensation is provided in the form of a gift debit/credit card (ClinCard). If a participant 
completes all visits, total compensation will range from $725-$845 depending on the arm they 
are randomized to. In the event gift debit/credit cards (ClinCard) are unavailable, gift card 
reimbursement may be used instead. 

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21. Data Management and Confidentiality
21.1 Steps taken to secure data
All faculty and staff at the Hope Clinic receive HIPAA, human participants, and EHSO training as 
part of their onboarding and continuing training. Each participant will be assigned a unique 
study participant identification number (PTID) and these numbers rather than names will be 
used to collect and store participant information, including omics data. 
Investigators and study personnel will keep accurate records to ensure that the conduct of the 
study is fully documented. Clinical data from this study, including participant birthdate and 
demographics, will be associated with the PTID, maintained on a HIPAA compliant clinical 
management database and a HIPAA compliant RedCap database and/ or password protected 
Excel file, respectively at Hope Clinic accessible to investigators and study personnel only. Hard 
copy clinical data forms, for example source or protocol-specific CRFs, associated with the PTID 
will be stored  at Hope Clinic in a locked filed cabinet and accessible to investigators and clinical 
staff only. A file linking the participant PII (i.e., their name and contact information) to their 
PTID will be maintained at the Hope Clinic in a separate locked file cabinet and HIPAA compliant 
clinical management database accessible to investigators and clinical staff only. Study personnel 
will only send documents containing personal PII via fax or encrypted email in accordance with 
HIPAA regulations (e.g., to send/receive safety lab data and medical records request to/from 
primary care provider).
21.2 Quality Control 
The Principal Investigator (or designee) will keep accurate records to ensure that the conduct of 
the study is fully documented. The investigator will ensure that all CRFs and participant study 
files are legible and complete for every participant. The Principal Investigator (or designee), 
through the use of an internal Quality Management Plan, appropriate site quality control, and 
quality assurance monitoring staff, will be responsible for the regular review of the conduct of 
the study for verifying adherence to the protocol, and for confirming the completeness,  
consistency, and accuracy of all documented data and accuracy of source documentation 
verification. All charts will be 100% Quality Controlled. The first five volunteers enrolled will 
receive a 100% Quality Assurance review. The reports of the internal site monitor will be 
submitted to the Principal Investigator (or designee). The RedCap data entry system will include 
checks for data that are outside feasible limits (e.g., dates that are in the future) or skipped 
answers.
21.3 Data and specimen handling
All de-identified samples will be stored at the Hope Clinic by laboratory staff using only the study 
number, PTID, date of visit, and visit number. Data regarding safety and adverse events will be 
maintained at the Hope Clinic of Emory University. Data from immunological assays and gene 
expression analysis (RNA sequencing) will be linked to PTID, maintained by 
 
laboratory at Stanford University, and accessible to investigators and laboratory staff. Laboratory 

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data and demographic data may be linked by PTID for statistical analysis by investigators or 
collaborators (e.g., to control for age); however, PTID will not be published nor will the gene 
expression (RNA sequencing) data be linked to demographic data in order to protect participant 
privacy and prevent the discovery of participant identity.
Specimens and demographic data linked by PTID will be stored indefinitely, but all personal 
identifiable information (PII) and PII/PTID links will be destroyed once the laboratory analysis 
associated with this protocol is complete and the last manuscript associated with this protocol 
has been published.
Study investigators and personnel will maintain the highest degree of confidentiality for the 
clinical and research information obtained from the participants. Medical and research records 
will be maintained in the strictest confidence. However, as a part of the quality assurance and 
legal responsibilities of a clinical study, investigators will permit authorized representatives of 
regulatory authorities to examine (and when required by applicable law, to copy) clinical records 
for the purpose of quality assurance reviews and evaluations of study safety and progress. Unless 
required by laws that permit copying of records, only the PTID associated with documents or with 
other participant data may be copied (and all personally identifying information will be removed). 
Authorized representatives described above are bound to maintain the strict confidentiality of 
medical and research information that is linked to identify individuals.
Blood tubes will be labeled at the Hope Clinic with a unique identifier and will be transported to 
the lab at the Hope Clinic in EHSO-approved transport containers.
22. Plans to Monitor the Data to Ensure Safety of Participants and Data Integrity
☒ More than minimal risk – Continue below.
Review our Data and Safety Monitoring Questionnaire and insert the relevant monitoring table 
at the end of this section. Also upload the completed questionnaire in the “Basic Study 
Information” smartform section in eIRB, question #8, as a separate document. 
Mark the risk categorization, as determined by the Data and Safety Monitoring Questionnaire, 
that applies to your study below:
Select one of the following (do not delete this table; review the guidance document 
for definitions):
☒ Medium Complexity
☐ High Complexity Category A
☐ High Complexity Category B

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If choosing this category for a study under an IND or IDE because you believe 
the study intervention does not significantly impact morbidity or mortality, 
please provide your rationale:
DSMP Requirement
How this Requirement is 
Met 
Frequency
Responsible 
Party(ies)
Real-time review of 
participant data during 
initial data collection.
100% QC review by 
CRC/CRN and peer review 
within 3 business days. QM 
will review first 5 
participants in real time.
Expectation is that this 
happens every time 
you obtain 
information.
CRC/CRNs 
QM 
Manager/Team
Site Monitoring at pre-
determined intervals: 
The Principal 
Investigator has a 
responsibility to 
ensure that the study is 
following all aspects 
of the protocol. 
There should be a standard 
operating procedure to 
review data (whether a 
sample or 100%) at pre-
determined intervals to 
ensure that there is adequate 
documentation of critical 
elements such as eligibility 
criteria. Monitoring is 
required at the following 
timepoints (but may be done 
more frequently):

study initiation  

at least every six 
months while 
participants are 
receiving intervention 
and 

annually while 
participants are in 
follow-up
At a minimum, a 
review is required 
annually when no one 
has been enrolled or 
the study is in long 
term follow up. 
Additional risk-based 
interim monitoring 
may be required at 
least once every 12-24 
weeks based on the 
site activity, to include 
the possibility of 
remote monitoring. A 
longer frequency could 
be acceptable with 
justification about risk 
to participants.
Delegate a 
responsible 
party for each 
requirement 
below. Self-
assessment is 
acceptable*.
Self-
assessment: a 
process for 
self-
assessment of 
protocol 
compliance 
and data 
integrity which 
can be part of 
an overall 
DSMP. See 
CTAC’s self-
assessment 
tool on their 
webpage. 
100% review of 
regulatory files
Site QM will conduct 100% 
review of reg files at the 
beginning and at close-out 
visit at a minimum. 
Reviewed at a 
minimum of first and 
close-out visits
QM 
Manager/Team
Regulatory 
Team

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100% review of 
consent forms
CRC/CRNs will perform 
peer review in real time for 
100% of ICFs.
QM will conduct 100% 
review of ICFs.
CRC/CRNs
QM 
Manager/Team
Review of credentials, 
training records, the 
delegation of 
responsibility logs (if 
applicable)
QM and Regulatory Team 
will conduct 100% review of 
credentials/training 
records/DoA files quarterly 
at a minimum.
QM 
Manager/Team
Regulatory 
Team
Comparison of case 
report forms (CRF) to 
source documentation 
for accuracy and 
completion
QM will conduct 100% 
review for first 5 participants 
in real time and on a monthly 
basis throughout the study.
QM 
Manager/Team
Review of 
documentation of all 
adverse events
SAEs will be reviewed by PI 
and designee and peer 
reviewed by CRC/CRNs and 
verified by QM team and 
evaluated by the ISM and 
Emory IRB. 
CRC/CRNs
QM 
Manager/Team
Monitoring of critical 
data points (eligibility, 
study endpoints, etc.)
QM will conduct 100% 
review for first 5 participants 
in real time and on a monthly 
basis throughout the study.
QM 
Manager/Team
Laboratory review of 
processing and storage 
of specimens
Peer review of sample log in 
done in real time and 
answering queries regularly 
Reviewed at first and 
close-out visits and at 
least biannually
Lab Manager 
or designee
Assessment of 
laboratory specimens 
stored locally
Peer review of sample log in 
done in real time and 
answering queries regularly- 
shipment done within 2 
weeks
Lab Manager 
or designee
Test article 
accountability review
Day to day and monthly per 
IDS pharmacist
Reviewed at first and 
close-out visits and at 
least biannually
Research 
Pharmacist
Accountability logs, 
dispensing records, 
and other participant 
records 
Monthly per IDS pharmacist
At least biannually
Research 
Pharmacist

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For FDA regulated 
studies, the following 
requirements apply:
Timing, frequency, 
and intensity of 
monitoring
Monitoring methods 
(may include 
centralized, on-site, 
and self-assessment)
Monitoring visits will 
include, but are not limited 
to, review of regulatory files, 
accountability records, 
electronic case report forms 
(eCRFs), ICFs, medical and 
laboratory reports, site study 
intervention storage records, 
training records, and protocol 
and GCP compliance. Site 
monitors will have access to 
each participating site, study 
staff and all study 
documentation according to 
the Hope Clinic CQMP. 
Study monitors will meet 
with all participating site PIs 
to discuss any problems and 
outstanding issues and will 
document site visit findings 
and discussion.
Monitoring visits are 
expected to occur 
monthly or bimonthly. 
Details of clinical site 
monitoring are 
documented in a 
clinical monitoring 
plan (CMP). The CMP 
describes in detail who 
will conduct the 
monitoring, at what 
frequency monitoring 
will be done, at what 
level of detail 
monitoring will be 
performed, and the 
distribution of 
monitoring reports.
Monitoring for 
this study will 
be performed 
by the QM 
team.
*For international studies, you are required to engage a CRO that is working in the site country 
and/or to consult with Emory’s legal counsel regarding compliance with the country’s clinical 
research regulations.
22.1 Study Oversight
The Principal Investigator and the research team (co-Investigators, research nurses, study 
coordinators, and data managers) are responsible for identifying adverse events. Adverse 
events will be reviewed regularly by the research team.
22.2 Adverse Events
This section defines the types of adverse events that may occur, and outlines the procedures 
for appropriate adverse event collecting, grading, recording, and reporting.
Information in this section complies with 21CFR 312; ICH Guideline E2A: Clinical Safety Data 
Management: Definitions and Standards for Expedited Reporting and Good Clinical Practice; 
and applies the standards set forth in the National Cancer Institute (NCI), Common Terminology 
Criteria for Adverse Events Version 5.0 [Published: November 27, 2017; 
http://evs.nci.nih.gov/ftp1/CTCAE/About.html]. These criteria have been reviewed by the study 
investigators and have been determined to be appropriate for this study population.

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22.2.1 Safety Reporting
22.2.2 Adverse Events
An adverse event (also referred to as an adverse experience) can be any unfavorable and 
unintended sign, symptom, or disease temporally associated with the use of the procedure, 
without any judgment about causality.
After vaccination, the following adverse events in the indicated intervals may be reported to 
Vaccine Adverse Event Reporting System (VAERS).
-
Anaphylaxis or anaphylactic shock (7 days)
-
Shoulder Injury Related to Vaccine Administration (7 days)
-
Vasovagal syncope (7 days)
-
Any acute complication or sequelae (including death) of above events (interval - not 
applicable)
-
Events described in manufacturer’s package insert as contraindications to additional 
doses of vaccine: hypersensitivity, including severe allergic reactions after previous dose 
of influenza vaccine
22.2.3 Suspected Adverse Reaction (SAR)
Suspected adverse reaction means any adverse event for which there is a reasonable possibility 
that the drug or procedure caused the adverse event. Suspected adverse reaction implies a 
lesser degree of certainty about causality than adverse reaction, which means any adverse 
event caused by a drug.
SARs after vaccine administration may include:
-
Local reactions: injection site redness, injection site swelling, pain at the site of injection, 
itching of the skin at the injection site.
-
Systemic reactions: headache, fever, nausea, dizziness.
SARs after phlebotomy may include:
-
Local reactions: pain at the site of venipuncture, bruising at the site of venipuncture, 
infection at the site of venipuncture
-
Systemic reactions: lightheadedness or fainting
22.2.4 Serious Adverse Event (SAE) or Serious Suspected Adverse Reaction
An adverse event or suspected adverse reaction is considered ‘‘serious’’ if, in the view of the 
investigator, it results in any of the following outcomes:
-
Death
-
A life-threatening adverse event
-
Inpatient hospitalization or prolongation of existing hospitalization
-
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions
-
A congenital anomaly/birth defect

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Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the participant and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Serious adverse events will be reported and 
recorded for the entire duration of the study.
An adverse event or suspected adverse reaction is considered ‘‘life-threatening’’ if, in the view 
of the investigator, its occurrence places the patient or participant at immediate risk of death. It 
does not include an adverse event or suspected adverse reaction that, had it occurred in a more 
severe form, might have caused death.
Any serious adverse event (for duration of study) will be recorded and reported within 24 hours 
to ISM.
22.2.5 Unexpected Adverse Event or Unexpected Suspected Adverse Reaction
An adverse event or suspected adverse reaction is considered ‘‘unexpected’’ if it is not listed in 
the Summary of Product Characteristics or is not listed at the specificity or severity that has 
been observed; or, if the Summary of Product Characteristics is not required or available, is not 
consistent with the risk information described in the general investigational plan or elsewhere 
in the current application, as amended.
22.2.6 Independent Safety Monitoring
The ISM, is a physician with relevant expertise in clinical studies whose primary responsibility 
will be to provide independent safety monitoring in a timely fashion and to provide 
recommendations regarding the safe continuation of this study.
The ISM will evaluate safety data generated from study participants against the known safety 
profile of the study product or study procedure to assess for possible changes to the overall risk 
of the study.
The ISM will communicate with the Principal Investigator as needed. The study has provisions 
for a back-up ISM to ensure that independent safety monitoring happens at all times during the 
study.
22.2.7 Collecting and Recording Adverse Events and Pregnancy
Adverse events may be identified during this study through any of these methods:
-
Examination of the participant during study visits.
-
Questioning the participant during study visits.
-
Receiving a safety contact from the participant at any time during the study
Note: participants will be asked to call the site if they develop any of the following:

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-
Any adverse event that limits self-care activities of daily living (e.g. bathing, dressing and 
undressing, feeding self, using the toilet, taking medications, and not bed ridden) even if 
he/she decides not to seek medical care
Reactogenicity of any grade is collected for 7 days after vaccination.
Serious adverse events will be recorded if they occur at any time during the study. 
A complete recording of safety events in the CRF will include event term; date(s) of onset and 
resolution/stabilization; assessment of severity; relationship to procedures/intervention(s); 
expectedness; determination of whether the AE qualifies as serious or non-serious; treatment 
required; action taken with study  articipation; and outcome. AEs qualifying as serious also 
require a narrative of the event. Updates in safety events will be recorded as additional 
information becomes available.
Information on pregnancies will be collected from the time a participant signs the consent until 
the participant completes study participation. If a participant becomes pregnant after study 
entry, the investigator will discuss with the participant and/or the treating provider the known 
possible risks to the fetus. Participants becoming pregnant after study entry will be withdrawn 
from the study and followed until the end of the pregnancy for safety. A pregnancy resulting in 
congenital anomaly/birth defect will be considered a SAE. Any premature termination of the 
pregnancy will also be reported and assessed as an SAE as needed.
22.3 Grading and Attribution of Adverse Events
22.3.1 Grading Criteria
Adverse events will be graded according to the criteria set forth in the National Cancer Institute’s 
Common Terminology Criteria for Adverse Events Version 5.0 [November 27, 2017; 
http://evs.nci.nih.gov/ftp1/CTCAE/About.html] This document (referred to herein as the NCI-
CTCAE manual) provides a common language to describe levels of severity, to analyze and 
interpret data, and to articulate the clinical significance of all adverse events. All adverse events 
whether or not listed in the NCI-CTCAE will be graded on a scale from 1 to 5 according to the 
following standards in the NCI-CTCAE manual (A semicolon indicates ‘or’ within the description 
of the grade):
-
Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.
-
Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADL*.
-
Grade 3 Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL**.
-
Grade 4 Life-threatening consequences; urgent intervention indicated.
-
Grade 5 Death related to AE.

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*Instrumental Activities of Daily Living (ADL) refer to preparing meals, shopping for groceries or 
clothes, using the telephone, managing money, etc.
**Self-care Activities of Daily Living (ADL) refer to bathing, dressing and undressing, feeding 
self, using the toilet, taking medications, and not bedridden.
Not all Grades are appropriate for all AEs; therefore, some AEs are listed with fewer than five 
options for Grade selection.
Anaphylaxis is a disorder characterized by an acute inflammatory reaction resulting from the 
release of histamine and histamine-like substances from mast cells, causing a hypersensitivity 
immune response. Clinically, it presents with breathing difficulty, dizziness, hypotension, 
cyanosis and loss of consciousness and may lead to death. Severity grading of anaphylaxis as 
per the NCI-CTCAE manual is as follows:
-
Grade 1= not applicable
-
Grade 2= not applicable
-
Grade 3= Symptomatic bronchospasm, with or without urticaria; parenteral intervention 
indicated; allergy-related edema/angioedema; hypotension
-
Grade 4= Life-threatening consequences; urgent intervention indicated
-
Grade 5= Death
Severity grading of AEs of laboratory abnormalities will be assessed as per the NCI-CTCAE
manual.
22.3.2 Definition of Attribution
The site investigator will initially determine the relationship of an adverse event. The 
relationship of an AE to study participation will be determined is RELATED or UNRELATED. 
22.3.3 Reporting Timelines
Reporting Serious Adverse Events to the Independent Safety Monitor
The Principal Investigator will notify the ISM by email of any SAE within 24 hours of becoming 
aware of the event. The ISM may request further information if necessary and possibly request 
changes to the protocol or consent form as a consequence of the adverse event.
Notifying Institutional Review Board
The Principal Investigator will ensure the timely dissemination of SAE information, including 
SAEs requiring expedited review by the ISM and to the IRB in accordance with IRB regulations 
and guidelines. Serious adverse events that are unanticipated, related to study participation, 
and involving risk to participant or others will be reported to the IRB  within 10 business days of 
event occurrence or of the PI becoming aware of the event per IRB guidelines.
22.4 Stopping Rules

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Study Stopping Rules:
Study procedures will be suspended pending expedited review of all pertinent data by the 
institutional review board and the ISM if Atorvastatin or QIV were recalled by the 
manufacturer.
Also, procedures will be suspended pending review of all pertinent data by the ISM after the 
occurrence of any of the following:
-
1 case of statin-induced necrotizing autoimmune myopathy
-
1 case of acute liver injury
-
2 cases of severe myalgia
Individual participant Stopping Rules:
Early study termination will occur in participants due to any of the following circumstances 
detailed in Section 16.
Conditions for continuation of treatment or early termination of treatment/Follow-up:
Please refer to Section 17.
Follow-up After Early Study Termination:
Participants who are prematurely terminated from the study due to an AE will be followed until 
resolution of the AE or until 28 days after a participant terminates from the study. Resolution of 
an AE is defined as the return to baseline status or as stabilization of the condition with the 
expectation that it will remain chronic.
After assessing terminated participants for safety under the provisions stated above, the subject 
will be seen in clinic, if necessary.
Participant Replacement
In the case of premature termination (Day 8 or earlier), extra participants may be recruited, at 
the discretion of the Principal Investigator, to maintain the target sample size.
22.5 Protocol Deviations
Deviations occur when the investigators, study staff, or participants fail to adhere to protocol 
requirements or when there is non-adherence to GCP guidelines.
Upon determination that a protocol deviation has occurred, the study staff will notify the 
Principal Investigator promptly. Substantive protocol deviations from the protocol that affect 
rights, safety or welfare of participants , their willingness to continue in the study or impact the 
integrity of the research data will be reported promptly to the IRB per IRB regulations.
23. Provisions to Protect the Privacy Interest of Participants

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A participant’s privacy and confidentiality will be respected throughout the study. Each 
participant will be assigned a unique patient identification number (PTID) and these numbers 
rather than names will be used to collect and store participant information and samples. A file 
linking the participant identity, i.e., name, to their unique study participant ID (PTID) is 
maintained at the Hope Clinic in a separate locked file cabinet and on a HIPAA compliant clinical 
management database. Screening, consenting, and study visits will take place in private clinic
rooms.
Any publications from this study will not use information that will identify participants by name 
or PTID. A description of this trial will be available on http://www.ClinicalTrials.gov, as required 
by US Law. This web site will not include information that can identify participants . At most, this 
web site will include a summary of the results. Site personnel will only transmit documents 
containing personal identifiable information (PII) using encrypted email or fax in accordance with 
HIPAA regulations (e.g., to send/receive safety lab data and medical records to/from primary care 
provider).
24. Economic Burden to Participants
There is no cost to participants for the research tests, procedures, or study product while taking 
part in this study. Procedures and treatment for clinical care may be billed to the participant , 
participant’s insurance or third party. Participants may be compensated for their participation in 
this study. Compensation will be in accordance with the local IRB policies and procedures, and 
participant to IRB approval.
If it is determined by the principal investigator that an injury occurred to a participant as a direct 
result of the tests, procedures or treatments that are done for this study, then referrals to 
appropriate health care facilities will be provided to the participant. Study personnel will try to 
reduce, control, and treat any complications from this study. Immediate medical treatment may 
be provided by the participating site. No financial compensation will be provided to the 
participant for any injury suffered due to participation in this study.
25. Informed Consent 
25.1 Statement of Compliance
This study was designed to ensure the protection of participants according to the ethical 
principles of the Declaration of Helsinki and amendments concerning medical research in human 
participants. This clinical study will be conducted using current good clinical practice and 
according to the criteria specified in this study protocol. Before study initiation, the protocol and 
the informed consent documents will be reviewed and approved by the IRB, as well as any other 
appropriate health authorities. Any amendments to the protocol or to the consent materials will 
also be approved by the appropriate bodies listed above prior to implementation.
25.2 Informed Consent Process

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The informed consent form will provide information about the study to a prospective participant 
to allow for an informed decision about participation in the study. Prospective participants must 
be given ample opportunity to review the informed consent and inquire about the results of the 
study. The consent form will be provided electronically to the prospective participant during the 
first screening phone call. A copy of the informed consent form will again be provided to a 
participant for review prior to any study procedure during the in person screening visit. The 
Principal Investigator or an approved designee will discuss the consent with the prospective 
participant and answer questions. Study staff will read through the consent form with potential 
participants and answer any questions. Participants will be allowed sufficient time to consider 
participation in the study, after having the nature and risks of the trial explained to them and 
have the opportunity to discuss the trial with their family, friends. The prospective participant 
will be told that being in the study is voluntary and that he or she may withdraw from the study 
at any time, for any reason. The consenting process will take place in private exam rooms at the 
Hope Clinic. We anticipate that the consent process will take about 30-60 minutes.
All participants must read, sign, and date a consent form before undergoing any study 
procedures. Consent materials will be provided in the English language, however, shortforms 
and a qualified interpreter are available and IRB approval will be requested for use in 
consenting non-English speaking participants. A copy of the signed consent form will be given 
to the participant. The informed consent form will be revised and receive IRB approval 
whenever important new safety information is available, whenever the protocol is amended, 
and/or whenever any new information becomes available that may affect participation in the 
study. 
Participants will be compensated for their time and travel. The informed consent
form will specify the amount of compensation for each participant.
26. Setting
Potential participants will be recruited and screened from the general population of metro 
Atlanta. Participants will be enrolled at the Hope Clinic, Decatur, Georgia.
27. Resources Available
The Hope Clinic has a database of more than 5000 previous volunteers who can be considered 
for screening for the study. The Hope Clinic also has a website and the ability to reach out to 
potential participants through advertising around the Emory University campus.
27.1 Facilities
The Hope Clinic is a community-based vaccine research clinic and is the clinical arm of the 
Emory Vaccine Center. The Winship Cancer Institute is the only National Cancer Institute–
Designated Comprehensive Cancer Center in Georgia and one of only 50 in the country.

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27.2 Participant Support
Referrals to appropriate medical or psychological health care facilities will be provided by the 
investigators to the participant as needed due to the anticipated consequences of human 
research. Study personnel will try to reduce, control, and treat any complications from this 
study. Immediate medical treatment may be provided by the relevant site (Hope Clinic or 
Winship).
27.3 Study Personnel Training
All faculty and staff at the Hope Clinic receive HIPAA, human participants , and EHSO (e.g., 
bloodborne pathogens) training as part of their onboarding and continuing training. In addition, 
all study personnel will complete ongoing approved protocol review and provide 
documentation of this training to study quality management personnel.
28. References
1.
Taylor FC, Huffman M, Ebrahim S. Statin therapy for primary prevention of 
cardiovascular disease. Jama 2013;310(22):2451-2. (In eng). DOI: 
10.1001/jama.2013.281348.
2.
Blanco-Colio LM, Tuñón J, Martín-Ventura JL, Egido J. Anti-inflammatory and 
immunomodulatory effects of statins. Kidney Int 2003;63(1):12-23. (In eng). DOI: 
10.1046/j.1523-1755.2003.00744.x.
3.
Jain MK, Ridker PM. Anti-inflammatory effects of statins: clinical evidence and basic 
mechanisms. Nat Rev Drug Discov 2005;4(12):977-87. (In eng). DOI: 10.1038/nrd1901.
4.
Bu DX, Griffin G, Lichtman AH. Mechanisms for the anti-inflammatory effects of statins. 
Curr Opin Lipidol 2011;22(3):165-70. (In eng). DOI: 10.1097/MOL.0b013e3283453e41.
5.
Chalmers JD, Short PM, Mandal P, Akram AR, Hill AT. Statins in community acquired 
pneumonia: Evidence from experimental and clinical studies. Respir Med 
2010;104(8):1081-91. (In eng). DOI: 10.1016/j.rmed.2010.04.005.
6.
Mehrbod P, Omar AR, Hair-Bejo M, Haghani A, Ideris A. Mechanisms of action and 
efficacy of statins against influenza. Biomed Res Int 2014;2014:872370. (In eng). DOI: 
10.1155/2014/872370.
7.
Fedson DS. Treating influenza with statins and other immunomodulatory agents. 
Antiviral Res 2013;99(3):417-35. (In eng). DOI: 10.1016/j.antiviral.2013.06.018.
8.
Dobesh PP, Klepser DG, McGuire TR, Morgan CW, Olsen KM. Reduction in Mortality 
Associated with Statin Therapy in Patients with Severe Sepsis. Pharmacotherapy: The 
Journal of Human Pharmacology and Drug Therapy 2009;29(6):621-630. DOI: 
https://doi.org/10.1592/phco.29.6.621.
9.
Sato R. Sterol metabolism and SREBP activation. Arch Biochem Biophys 
2010;501(2):177-81. (In eng). DOI: 10.1016/j.abb.2010.06.004.
10.
Luo W, Adamska JZ, Li C, et al. SREBP signaling is essential for effective B cell responses. 
Nat Immunol 2023;24(2):337-348. (In eng). DOI: 10.1038/s41590-022-01376-y.

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Version: 2.0 (10/11/2023)
IRB Form BIO 
11.
Black S, Nicolay U, Del Giudice G, Rappuoli R. Influence of Statins on Influenza Vaccine 
Response in Elderly Individuals. J Infect Dis 2016;213(8):1224-8. (In eng). DOI: 
10.1093/infdis/jiv456.
12.
McLean HQ, Chow BDW, VanWormer JJ, King JP, Belongia EA. Effect of Statin Use on 
Influenza Vaccine Effectiveness. The Journal of Infectious Diseases 2016;214(8):1150-
1158. DOI: 10.1093/infdis/jiw335.
13.
Omer SB, Phadke VK, Bednarczyk RA, Chamberlain AT, Brosseau JL, Orenstein WA. 
Impact of Statins on Influenza Vaccine Effectiveness Against Medically Attended Acute 
Respiratory Illness. J Infect Dis 2016;213(8):1216-23. (In eng). DOI: 
10.1093/infdis/jiv457.
14.
Tsai LW, Chen YT, Shih CJ, Ou SM, Chao PW, Lo SH. Statin Use and Influenza Vaccine 
Effectiveness in Persons >65 Years of Age, Taiwan. Emerg Infect Dis 2020;26(6):1243-50. 
(In eng). DOI: 10.3201/eid2606.190646.
15.
Ortiz JR, Neuzil KM, Shay DK, et al. The burden of influenza-associated critical illness 
hospitalizations. Crit Care Med 2014;42(11):2325-32. (In eng). DOI: 
10.1097/ccm.0000000000000545.
16.
Vieira-Silva S, Falony G, Belda E, et al. Statin therapy is associated with lower prevalence 
of gut microbiota dysbiosis. Nature 2020;581(7808):310-315. (In eng). DOI: 
10.1038/s41586-020-2269-x.
17.
Oh JZ, Ravindran R, Chassaing B, et al. TLR5-mediated sensing of gut microbiota is 
necessary for antibody responses to seasonal influenza vaccination. Immunity 
2014;41(3):478-492. (In eng). DOI: 10.1016/j.immuni.2014.08.009.
18.
Pulendran B, Li S, Nakaya HI. Systems vaccinology. Immunity 2010;33(4):516-29. (In 
eng). DOI: 10.1016/j.immuni.2010.10.006.
19. 
Martín-Ventura JL, Blanco-Colio LM, Gómez-Hernández A, et al. Intensive treatment 
with atorvastatin reduces inflammation in mononuclear cells and human atherosclerotic 
lesions in one month. Stroke. 2005 Aug;36(8):1796-800. doi: 
10.1161/01.STR.0000174289.34110.b0. Epub 2005 Jul 14. PMID: 16020773.
20. 
McLean HQ, Chow BD, VanWormer JJ, et al. Effect of Statin Use on Influenza Vaccine 
Effectiveness. J Infect Dis. 2016 Oct 15;214(8):1150-8. doi: 10.1093/infdis/jiw335. Epub 
2016 Jul 28. PMID: 27471318; PMCID: PMC5034952.
21. 
Chung H, Campitelli MA, Buchan SA, et al. Evaluating the Impact of Statin Use on 
Influenza Vaccine Effectiveness and Influenza Infection in Older Adults. Clin Infect Dis. 
2023 Jul 26;77(2):303-311. doi: 10.1093/cid/ciad148. PMID: 36942534; PMCID: 
PMC10371308.
22. 
Newman CB, Preiss D, Tobert JA, et al. Statin Safety and Associated Adverse Events: A 
Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc 
Biol. 2019 Feb;39(2):e38-e81. doi: 10.1161/ATV.0000000000000073. Erratum in: 
Arterioscler Thromb Vasc Biol. 2019 May;39(5):e158. PMID: 30580575.

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IRB Form BIO 
Appendix A. Schedule of Procedures
 
-60 to   
-32
-31 to  
-29 
1
2
4
8±
1
15
±2
29±
3
91±
7
181
±15
Phone 
call^
 V 1
V2
V3
V4
V5
V6
V7
V8
V9
V10
Informed consent
x
Demographics, medical 
history
x
Interim medical history
x
x
x
x
x
x
x
x
x
x
Medications
x
x
x
x
x
x
x
x
x
x
x
Targeted physical exam
(x)
(x)
(x)
(x)
(x)
(x)
(x)
(x)
(x)
(x)
Vital signs
(x)
(x)
(x)
(x)
(x)
(x)
(x)
(x)
(x)
(x)
Blood draw for screening
x
Stool Sample collection
x
x
x
Pregnancy test 
(if applicable)
x
x
(x)
(x)
(x)
(x)
(x)
(x)
(x)
Vaccination
x
Statin therapy*
x
x
x
x
x
x
x
Memory Aid
x
x
x
Blood draw for 
immunological assays
x
x
x
x
x
x
x
x
x
x
Clinical labs for statin 
therapy
x
x
x
Adverse events
x
x
x
x
x
x
x
x
Serious adverse events
x
x
x
x
x
x
x
x
x
Conducting a visit outside window is allowed at investigator discretion
Parentheses indicate a given procedure will be conducted if relevant for the visit: vital signs and 
pregnancy testing if applicable will be on the day of screening, prior to statin therapy initiation 
and prior to vaccination.
*Each participant receiving statin therapy will have clinical labs drawn. The tests conducted will 
be: Lipid profile, Creatinine Phosphokinase, Liver function tests, CRP. These tests will be valid 
for 30 days.
^phone call is completed 15 days after initiation of statin therapy.