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| Name | Class |
|---|---|
| Max Delbrück Center for Molecular Medicine (MDC), Berlin | UNKNOWN |
| Labor Berlin, Germany | UNKNOWN |
| Experimental & Clinical Research Center Berlin | UNKNOWN |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control (no intervention) | No Intervention | Four weeks of ad libitum eating pattern with eating time window >11 h/day. No change of the regular eating pattern. | |
| TRE | Experimental | Four weeks of TRE, where the daily eating pattern is reduced to 8 h/day. The first meal will be before 10:00 AM. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TRE: Time-restricted eating | Behavioral | The daily eating pattern is reduced to 8 h/day. The first meal will be before 10:00 AM. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Autophagic flux in PBMCs | Change in autophagic flux in peripheral immune cells from baseline (V1) to four weeks (V2), comparing the TRE group versus control, as measured by flow cytometry detection of LC3-II accumulation via antibody staining. | Change from baseline to 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in body weight | Change in body weight | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in body composition (BodPod) | Change in body composition (e.g., fat and lean body mass), assessed via Air Displacement Plethysmography (ADP, BodPod). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sebastian Hofer, Dr. rer. nat. | Contact | +493094062372 | sebastian.hofer@charite.de |
| Name | Affiliation | Role |
|---|---|---|
| Sebastian Hofer, Dr. rer. nat. | Clinical Research Unit, Experimental and Clinical Research Center, Charité, Berlin, Germany & Max-Delbrück Center for Molecular Medicine, Berlin, Germany | Principal Investigator |
| Anna Katharina Simon, Prof. Dr. | Max-Delbrück Center for Molecular Medicine, Berlin, Germany |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Research Unit, Experimental & Clinical Research Center, Campus Buch, Charité | Recruiting | Berlin | 13125 | Germany |
Individual participant data that underlie the results of reported articles (text, tables, figures, supplemental data) will be shared after deidentification.
Beginning 9 months and ending 36 months following article publication.
Researchers who provide a methodologically and scientifically sound proposal.
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| ID | Term |
|---|---|
| D005215 | Fasting |
| D000093763 | Intermittent Fasting |
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D005247 | Feeding Behavior |
| D001519 | Behavior |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| University of Oxford |
| OTHER |
| University of Cologne | OTHER |
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| Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in body composition (BIA) | Change in body composition (e.g., fat and lean body mass), assessed via bioimpedance analysis (BIA). | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in the differential blood count | Change in the differential blood count, assessed with Hematology analyzers. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in blood glucose levels | Change in blood glucose levels, assessed via routine blood diagnostic tests | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in insulin metabolism | Changes in insulin metabolism parameters, including insulin, IGF-1, C-peptide, ghrelin, leptin, adiponectin, and glucagon, assessed via ELISAs | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Changes in blood ketone body levels | Changes in blood ketone body levels (3-hydroxybutyrate, acetoacetate, acetone), assessed using commercially available assay kits | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in blood lipid profile | Changes in blood lipids assessed via metabolomics and routine blood diagnostic tests | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in liver or renal function | Changes in blood parameters of liver and renal function assessed via routine blood diagnostic tests | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in blood electrolyte levels | Changes in blood electrolyte levels assessed via routine blood diagnostic tests | 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 | Change in the incidence of clinically diagnosable infections during the study period, assessed at study visits by the study physician | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in continuous blood glucose levels | Change in continuous blood glucose levels, assessed with continuous glucose monitors (CGM). CGMs will be applied at V1 and V2 and record continuous glucose levels for 14 days each. | CGMs will be applied at V1 and V2 and record continuous glucose levels for 14 days each. |
| Change in grip strength | Change in grip strength, assessed with a dynamometer. Handgrip strength will be measured using a dynamometer three times sequentially and repeated after 1 hour. | Change from baseline to 4 weeks (end of TRE). |
| Change in metabolic rate | Change in metabolic rate via indirect calorimetry. Indirect calorimetry will be performed to assess energy expenditure as well as carbohydrate and fat oxidation rates. During the procedure, the subject will rest quietly in bed while wearing a ventilated hood. The hood is equipped with an inlet and an outlet valve. Through the inlet valve, the subject receives a constant supply of fresh air, while exhaled air is collected via the outlet valve. Sampling at the rear of the calorimetry device allows determination of gas concentrations in the ambient room air. By calculating the difference, oxygen consumption (VO₂) and carbon dioxide production (VCO₂) in ml/min are determined. These volumes enable the calculation of energy expenditure and substrate oxidation rates. This measurement is performed after a rest period of 30 minutes to determine resting fasting energy expenditure (duration approximately 30 minutes). | Change from baseline to 4 weeks (end of TRE). |
| Change in Sleep Quality | Change in Sleep Quality assessed using a questionnaire for the Pittsburgh Sleep Quality Index [PSQI]. | Change from baseline to 4 weeks (end of TRE) |
| Change in health-related quality of life | Change in EQ-5D-5L assessed using questionnaires. | Change from baseline to 4 weeks (end of TRE) |
| Change in ChronoType | Change in ChronoType assessed using the Munich ChronoType Questionnaire [MCTQ] | Change from baseline to 4 weeks (end of TRE) |
| Change in the Multidimensional Prognostic Index (MPI). | Change in the MPI for geriatric assessment. MPI assessments will be conducted, including documentation of medication and dietary supplement use, medication allergies, nutritional therapies, a range of disease symptoms, social history, activities of daily living (ADL), instrumental activities of daily living (IADL), malnutrition screening, the Short Portable Mental Status Questionnaire (SPMSQ), and the Exton Smith Scale (assessment of decubitus risk), all administered via standardized questionnaires. | Change from baseline to 4 weeks |
| Change in the walking speed. | A 10-meter walk test will be performed to determine walking speed in m/s. For this purpose, the subject will walk from a 0-meter mark to a 10-meter mark upon command. Timing will begin at the 2-meter mark. The procedure will be repeated three times, and the times will be averaged. If the subject's fitness level permits, the procedure will be repeated with the instruction to complete the 10 meters 'as fast as possible while still feeling safe'. | Change from baseline to 4 weeks |
| Change in proteome profiles in plasma and PBMCs. | Change in proteome profiles in plasma and PBMCs, measured by LC-MS mass spectrometry or Olink proteomics. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in metabolite patterns in plasma. | Change in metabolite patterns in plasma, assessed by untargeted (¹H-NMR) and/or targeted (LC-MS) metabolomics. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in metabolite patterns in stool. | Change in metabolite patterns in stool, assessed by untargeted (¹H-NMR) and/or targeted (LC-MS) metabolomics. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in metabolite patterns in urine. | Change in metabolite patterns in urine, assessed by untargeted (¹H-NMR) and/or targeted (LC-MS) metabolomics. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in gut microbiome composition. | Change in gut microbiome composition by metagenomic sequencing of stool. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in immune-cell subset distribution and activation. | Change in immune-cell subset distribution and activation, assessed by scRNA-seq and flow cytometry. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in body fat percentage. | Change in body fat percentage, measured by air-displacement plethysmography. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in office systolic and diastolic blood pressure. | Change in office systolic and diastolic blood pressure (mmHg), measured by non-invasive blood pressure cuff. | Change from baseline to 4 weeks |
| Change in pulse-wave velocity. | Change in pulse-wave velocity (m/s), measured by PulsePen. | Change from baseline to 4 weeks |
| Change in frequency of pro- and anti-inflammatory immune cells. | Change in frequency of pro- and anti-inflammatory immune cells in PBMCs, by flow cytometric immunophenotyping. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in immune-cell function. | Change in immune-cell function (cytokine production, proliferation) after in vitro stimulation of PBMC subsets, by flow cytometry. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in circulating pro- and anti-inflammatory cytokine concentrations in plasma. | Change in circulating pro- and anti-inflammatory cytokine concentrations in plasma, by multiplex cytokine assay. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in expression of senescence markers in immune-cell subsets. | Change in expression of senescence markers in immune-cell subsets, by flow cytometry. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in the hypusination status of eIF5A in PBMCs | Change in the hypusination status of eIF5A in PBMCs by flow cytometry. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in mTOR activity status in PBMCs | Change in mTOR activity status in PBMCs by flow cytometry. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in expression of key autophagy-regulatory genes. | Change in expression of key autophagy-regulatory genes in specific immune-cell types or bulk PBMCs, by qPCR, scRNA-seq, or bulk RNA-seq. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in energy metabolism in immune-cell subsets. | Change in cellular energy metabolism in immune-cell subsets, measured by Seahorse extracellular flux analysis and/or Scenith Assay in isolated immune cells ex vivo. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in coagulation. | Change in coagulation, assessed via e.g., thrombin generation, d-dimers from plasma | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in influenza-specific B- and T-cell responses. | Change in influenza-specific B- and T-cell responses in serum and PBMCs (e.g., ELISpot). | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in SARS-CoV-2 specific B- and T-cell responses. | Change in SARS-CoV-2 specific B- and T-cell responses in serum and PBMCs (e.g., ELISpot). | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in concentration of influenza-specific IgG antibodies. | Change in concentration of influenza-specific IgG antibodies, by ELISA. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in concentration of SARS-CoV-2 specific IgG antibodies. | Change in concentration of SARS-CoV-2 specific IgG antibodies, by ELISA. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in concentration of influenza-neutralizing antibodies. | Change in concentration of influenza-neutralizing antibodies. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in concentration of SARS-CoV-2 neutralizing antibodies. | Change in concentration of SARS-CoV-2 neutralizing antibodies. | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Change in DNA-break profiles in primary B cells. | Change in DNA-break profiles in primary B cells, assessed by SWIBRID (Switch-joint Breakpoint Repertoire Identification). | Change from baseline to 4 weeks (end of TRE), 2 weeks and 12-14 weeks after vaccination |
| Principal Investigator |
| D009976 |
| Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |