VITAL: Vaccination, Immunity, Time-restricted Eating, Aging and Lifestyle

Overview

The aim of this study is to investigate the effects of a four-week time-restricted eating (TRE) intervention on autophagy, immune function, and vaccine response to a seasonal influenza and COVID-19 vaccines in older healthy subjects.

Detailed description

Aging impairs immune cell autophagy and reduces vaccine efficacy, leaving older adults highly vulnerable to influenza and other infectious diseases. Time-Restricted Eating (TRE), by limiting daily food intake to an 8-hour window without detailed calorie counting, modulates nutrient-sensing pathways (e.g., mTOR inhibition, AMPK activation) and boosts autophagic flux in preclinical models. In a randomized, controlled trial, healthy volunteers aged 60-85 will follow either four weeks of TRE or their usual eating pattern. After that, all will receive a standard seasonal vaccines against influenza and COVID-19 outside of the trial at their general practitioner (min. 2 days and max. 14 days after the stop of intervention). Blood and physiologic measurements at baseline, after four weeks of study intervention will quantify autophagy in immune cells, metabolome/proteome shifts, body composition, blood pressure, and arterial stiffness, among others. At two additional visits after the vaccination (2 weeks and 12-14 weeks after the vaccination), immune responses to the vaccination will be monitored in the blood. The investigators hypothesize that TRE-induced restoration of autophagy and amelioration of immunosenescence will correlate with stronger vaccine responses, offering a simple, low-cost strategy to rejuvenate immunity and improve preventive care in the elderly.

Interventions

• Behavioral TRE: Time-restricted eating
  The daily eating pattern is reduced to 8 h/day. The first meal will be before 10:00 AM.

Primary outcome measures

• Autophagic flux in PBMCs [Time frame: Change from baseline to 4 weeks]

Secondary outcome measures (12)

• Change in body weight [Time frame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination]
• Change in body composition (BodPod) [Time frame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination]
• Change in body composition (BIA) [Time frame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination]
• Change in the differential blood count [Time frame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination]
• Change in blood glucose levels [Time frame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination]
• Change in insulin metabolism [Time frame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination]
• Changes in blood ketone body levels [Time frame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination]
• Change in blood lipid profile [Time frame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination]
• Change in liver or renal function [Time frame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination]
• Change in blood electrolyte levels [Time frame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination]
• Change in the incidence of clinically diagnosable infections during the study period [Time frame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination]
• Change in continuous blood glucose levels [Time frame: CGMs will be applied at V1 and V2 and record continuous glucose levels for 14 days each.]

Eligibility criteria

Inclusion criteria

• Male and female participants, enrolled in a 1:1 ratio
• Age 60-85 years
• Body mass index (BMI) 20-35 kg/m²
• Capacity to give informed consent
• Existing health insurance to allow evaluation and treatment of any incidental findings
• Usual daily eating window > 11 hours
• First meal of the day before 10:00 AM
• Willingness to receive seasonal influenza and COVID-19 vaccination and proof of scheduled appointment
• Willingness and ability to follow a prescribed TRE dietary regimen (8-hour daily eating window; 16-hour fast without any caloric intake)
• Appointment for simultaneous influenza and COVID-19 vaccination pre-arranged with primary care physician and coordinated with study team to align with TRE intervention

Exclusion criteria

• Any vaccination (especially influenza and/or COVID-19) within 6 months before the intervention start
• Vaccinations not related to the study, administered during the study period from V0 to V4
• History of influenza infection within 6 months prior to initiation of the study intervention
• History of severe adverse reactions to prior vaccinations
• Use of pharmacological weight-loss agents (e.g., semaglutide)
• Diabetes mellitus under ongoing pharmacological treatment
• Symptoms of systemic inflammatory or autoimmune disease
• Immunosuppression (including use of immunosuppressive drugs)
• Severe hypertension (systolic > 180 mmHg or diastolic > 110 mmHg)
• Diseases or functional disorders which, in the opinion of the study physician, preclude participation in the study
• Participation in any fasting intervention (e.g., TRE, alternate-day fasting, 5:2, 18:6) within 6 months before enrollment
• Participation in another diet or weight-loss program (e.g., intensive athletic training)
• Night-shift or rotating-shift work
• Severe, active, or unstable medical conditions requiring treatment
• Postoperative recovery phase
• Antibiotic therapy within 3 months before enrollment
• Acute or chronic infections
• Therapeutic or medically prescribed special diets
• Vegan diet
• Current smoker
• Weight change > 2 kg in the month before enrollment
• Known substance, drug, or alcohol abuse
• Anemia
• Claustrophobia
• Legal incapacity or any other circumstance that prevents full understanding of the nature, importance, and implications of the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Basic science

Study locations

Germany · 1 center

• Clinical Research Unit, Experimental & Clinical Research Center, Campus Buch, Charité — Berlin

Identifiers

NCT: NCT07000708 · EA4/154/24

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗