Clinical trial NCT07000708: VITAL: Vaccination, Immunity, Time-restricted Eating, Aging and Lifestyle
Official title: VITAL: Vaccination, Immunity, Time-restricted Eating, Aging and Lifestyle
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Vaccination
Immunosenescence
Metabolism
Keywords: fasting
vaccination
intermittent fasting
time-restricted eating
influenza
immunity
aging
immunosenescence
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Max Delbrück Center for Molecular Medicine (MDC), Berlin
name: Labor Berlin, Germany
name: Experimental & Clinical Research Center Berlin
name: University of Oxford
name: University of Cologne
First posted: 2025-06-03
Enrollment: 24
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 vaccine in older healthy subjects.

Detailed description: Aging impairs immune cell autophagy and reduces vaccine efficacy, leaving older adults highly vulnerable to influenza. 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 influenza vaccine 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.

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 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)
* Influenza-vaccination appointment pre-arranged with primary care physician and coordinated with study team to align with TRE intervention

Exclusion Criteria:

* Any vaccination (especially influenza) within 6 months before intervention start
* Influenza infection within 6 months before intervention start
* History of severe adverse reactions to prior vaccinations
* Symptoms of systemic inflammatory or autoimmune disease
* Immunosuppression (including use of immunosuppressive drugs)
* Severe hypertension (systolic \> 180 mmHg or diastolic \> 110 mmHg)
* Any medical condition or functional impairment that, in the investigator's judgment, precludes safe participation
* 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
* Chronic use of prescription medications (except hormonal contraception)
* Postoperative recovery phase
* Antibiotic therapy within 3 months before enrollment
* Acute or chronic infections
* Therapeutic or medically prescribed special diets
* Food intolerances
* 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

Primary outcomes:
measure: Autophagic flux in PBMCs
timeFrame: Change from baseline to 4 weeks
Secondary outcomes:
measure: Change in body weight
timeFrame: Change from baseline to 4 weeks
measure: Change in body composition (BodPod)
timeFrame: Change from baseline to 4 weeks
measure: Change in body composition (BIA)
timeFrame: Change from baseline to 4 weeks
measure: Change in proteome profiles in plasma and PBMCs.
timeFrame: Change from baseline to 4 weeks
measure: Change in metabolite patterns in plasma.
timeFrame: Change from baseline to 4 weeks
measure: Change in metabolite patterns in stool.
timeFrame: Change from baseline to 4 weeks
measure: Change in metabolite patterns in urine.
timeFrame: Change from baseline to 4 weeks
measure: Change in gut microbiome composition.
timeFrame: Change from baseline to 4 weeks
measure: Change in immune-cell subset distribution and activation.
timeFrame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination
measure: Change in body fat percentage.
timeFrame: Change from baseline to 4 weeks
measure: Change in office systolic and diastolic blood pressure.
timeFrame: Change from baseline to 4 weeks
measure: Change in pulse-wave velocity.
timeFrame: Change from baseline to 4 weeks
measure: Change in frequency of pro- and anti-inflammatory immune cells.
timeFrame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination
measure: Change in immune-cell function.
timeFrame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination
measure: Change in circulating pro- and anti-inflammatory cytokine concentrations in plasma.
timeFrame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination
measure: Change in expression of senescence markers in immune-cell subsets.
timeFrame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination
measure: Change in expression of key autophagy-regulatory genes.
timeFrame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination
measure: Change in energy metabolism in immune-cell subsets.
timeFrame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination
measure: Change in coagulation.
timeFrame: Change from baseline to 4 weeks
measure: Change in influenza-specific B- and T-cell responses.
timeFrame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination
measure: Change in concentration of influenza-specific IgG antibodies.
timeFrame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination
measure: Change in concentration of influenza-neutralizing antibodies.
timeFrame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination
measure: Change in the Multidimensional Prognostic Index (MPI).
timeFrame: Change from baseline to 4 weeks
measure: Change in DNA-break profiles in primary B cells.
timeFrame: Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Clinical Research Unit, Experimental & Clinical Research Center, Campus Buch, Charité
Study officials:
affiliation: Clinical Research Unit, Experimental and Clinical Research Center, Charité, Berlin, Germany & Max-Delbrück Center for Molecular Medicine, Berlin, Germany
name: Sebastian Hofer, Dr. rer. nat.
role: PRINCIPAL_INVESTIGATOR
affiliation: Max-Delbrück Center for Molecular Medicine, Berlin, Germany
name: Anna Katharina Simon, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: