Systems Biological Assessment of Statin Effect on Vaccine Responses

• ClinicalTrials.gov Identifier: NCT06024096
• Recruitment Status: Recruiting
• First Posted: September 5, 2023
• Last Update Posted: September 26, 2023
• Sponsor: Emory University
• Information provided by (Responsible Party): Daniel S. Graciaa, MD, Emory University

Study Description

Brief Summary:

This study is being done to answer the question: Does the use of statin lipid-lowering medication change the effect of influenza vaccine? The research team will use the knowledge gained from answering this question to understand how this medication affects long-lasting immune responses to vaccines. The researchers will study the immune response to the influenza vaccine in the blood (where antibodies are). The team will also look at how statin therapy affects the bacteria that live in the gut by collecting stool samples. To be in this research, participants must be adults willing to receive vaccines.

Condition or disease	Intervention/treatment	Phase
Vaccine Response	Drug: Atorvastatin; Biological: Quadrivalent seasonal influenza vaccine	Phase 4

Detailed Description:

Statins are widely used for their lipid-lowering and cardiovascular protective effects. Additional research has shown that statins can be anti-inflammatory and play a part in modulating the immune system. These effects are called into action in events such as pneumonia, influenza infection, and sepsis. This study will include a screening visit, a statin therapy initiation visit (if the participant is in the statin therapy group), a vaccination visit, and a series of follow-up visits. The statin medication will be dispensed by the study staff with clear instructions on how to take the medication for two months (one month prior to vaccination, and one month after vaccination). Other study procedures include a collection of medical history and medications taken, a urine pregnancy test for participants who are biologically able to become pregnant, a recording of vital signs, and a collection of any adverse events that the participant experiences during their participation in the study. The stool will be collected in one screening visit, at the vaccination visit, and one follow-up visit. Safety tests to evaluate muscle health and liver function will be obtained as well at screening and for participants selected to receive the statin therapy, at two follow-up visits. Memory Aid will be completed by the participant after vaccination.

The blood and stool samples collected during this study will be stored and tested to evaluate how the immune system responds to statin therapy and vaccination over time. The remaining unused samples will be stored for use in future research.

This research will help advance the knowledge that researchers have on how the immune system reacts to a vaccine if previously exposed to a statin therapy regimen. This will, in turn, enable us to identify the factors that help predict the extent of durability of protection gained from a specific vaccine. This may impact the way future vaccines are developed to provide long-lasting immunity against infections.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Systems Biological Assessment of Statin Effect on Vaccine Responses
• Actual Study Start Date: September 20, 2023
• Estimated Primary Completion Date: March 31, 2026
• Estimated Study Completion Date: March 31, 2026

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: seasonal quadrivalent influenza vaccine (QIV); Participants will receive the seasonal QIV	Biological: 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.; Other Name: Flu vaccine
Active Comparator: statin therapy and a seasonal quadrivalent influenza vaccine (QIV); Participants randomized to the Statin + QIV arm will be asked to come back for an extra visit one month prior to the date of vaccination to start statin therapy.	Drug: Atorvastatin; Atorvastatin is a lipid-lowering agent of the statin family that functions by blocking a rate-limiting enzyme, Hydroxymethylglutaryl-CoA (HMG-CoA) reductase, in 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.; Other Name: Statin Therapy; Biological: 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.; Other Name: Flu vaccine

Outcome Measures

Primary Outcome Measures :

1. Magnitude of the antibody (Ab) response to QIV in statin recipients and non-recipients. [ Time Frame: Up to 29 days after vaccine administration ]
   Magnitude of neutralizing antibody responses against influenza vaccine strains at 29 days after vaccination among participants.

Secondary Outcome Measures :

1. Frequency of adverse events (AEs) [ Time Frame: Until day 29 after vaccine administration ]
   Adverse events of grade 2 or higher (AE, defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the vaccine, without any judgment about causality) will be identified during questioning or examination of participants during study visits or receiving a safety contact from a participant.
2. Severity of adverse events (AEs) [ Time Frame: Until day 29 after vaccine administration ]
   Adverse events (AE) will be graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 5.0
3. Frequency of serious adverse events (SAEs) [ Time Frame: Up to 181 days after vaccine administration ]
   Serious adverse events (SAE, defined as an AE that in the view of the investigator results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect) will be identified during questioning or examination of participants during study visits or receiving a safety contact from a participant any time during the study.
4. Severity of serious adverse events [ Time Frame: Up to 181 days after vaccine administration ]
   SAE will be graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 5.0.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Able to understand and give informed consent.
• Age 18-50 years.
• Women of childbearing 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:

• History of allergy or serious adverse reaction, including Guillain-Barré syndrome, to a vaccine or vaccine products.
• 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.
• History of HIV, Hepatitis B, or Hepatitis C infection.

• 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 includes (but is not limited to):

  1. Insulin-dependent diabetes
  2. Severe heart disease (including arrhythmias)
  3. Severe lung disease
  4. Severe liver disease
  5. Severe kidney disease
  6. Severe hypertension: defined as life-threatening consequences (e.g., malignant hypertension, transient or permanent neurologic deficit).
• BMI > 30
• Current or previous use of statins or any other lipid-lowering drug.
• Pregnancy or breastfeeding or plans to become pregnant in the first 3 months of study participation.
• History of influenza infection within the same influenza season.
• Receipt of blood products or immune globulin products within the prior 3 months.
• 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.
• Receipt of any live vaccines 30 days before or plans to receive any live vaccines 30 days after vaccination.
• 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:

• The participant is currently taking any medication that has known interactions with statin therapy.
• History of renal or hepatic impairment.
• Abnormal Safety lab results >1.5 upper limit normal (ULN)

Contacts and Locations

Contacts

Contact: Daniel S. Graciaa, MD, MPH, MSc; 404-712-9018 or 404-712-1370; dsgraci@emory.edu

Locations

United States, Georgia

Hope Clinic; Recruiting

Atlanta, Georgia, United States, 30322

Contact: Daniel Graciaa, MD, MPH, MSc 404-712-9018 dsgraci@emory.edu

Principal Investigator: Daniel Graciaa, MD

Sponsors and Collaborators

Emory University

Investigators

• Principal Investigator: Daniel S. Graciaa, MD, MPH, MSc; Emory University
• Principal Investigator: Nadine Rouphael, MD; Emory University
• Principal Investigator: Varun Phadke, MD; Emory University
• Principal Investigator: Vin Tangpricha, MD, PhD; Emory University

More Information

• Responsible Party: Daniel S. Graciaa, MD, Assistant Professor, Emory University
• ClinicalTrials.gov Identifier: NCT06024096
• Other Study ID Numbers: STUDY00006239
• First Posted: September 5, 2023
• Last Update Posted: September 26, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The research team will share de-identified participant data (including data dictionaries) and Transcriptomics data.
• Supporting Materials: Study Protocol
• Time Frame: The team will share the data immediately following the study publication.
• Access Criteria: Data will be available via NCBI GEO
• URL: http://www.ncbi.nlm.nih.gov/geo/

• 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

Keywords provided by Daniel S. Graciaa, MD, Emory University:

Flu Vaccine; Statins; Immunization Response; seasonal quadrivalent influenza vaccine; antibody (Ab) response

Additional relevant MeSH terms:

Atorvastatin; Vaccines; Immunologic Factors; Physiological Effects of Drugs; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors