Therapeutic Fasting and Immune Aging (JÛVENILE)

Therapeutic Fasting and Immune Aging: A Pilot Study of Tolerance

Immunosenescence is the age-related decline of the immune system, involving a state of chronic inflammation and a decrease in the diversity/adaptability of the lymphocyte repertoire. The consequences of immunosenescence are multiple, including increased susceptibility to infections and poorer vaccine responses.

Study Overview

• Status: Not yet recruiting
• Conditions: Diet, Healthy; Fasting
• Intervention / Treatment: Dietary supplement: Fasting mimicking diet (FMD)

Detailed Description

In order to fight against immunosenescence, many therapeutics are envisaged, with the aim of restoring, renewing and/or reprogramming the immune system. Among these leads, therapeutic fasting, and in particular the "fasting mimicking diet" (FMD), seems to modify the reprogramming and renewal of the immune system with, on the one hand, the elimination of inefficient "overactivated" cells and, on the other hand, the activation of hematopoietic stem cells. FMD consists of a significant reduction in food intake, limited to 3-5 days/month. The FMD seems to be the best compromise between efficacy and tolerance (already evaluated in humans, including oncology).

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Baptiste GRAMONT, MD; Phone Number: +33 (0)0477829641; Email: Baptiste.Gramont@chu-st-etienne.fr
• Study Contact Backup: Name: Florence RANCON, CRA; Email: florence.rancon@chu-st-etienne.fr

Study Locations

• France
  • Le Chambon-Feugerolles, France, 42500
    • EHPAD Claudinon
    • Contact: Romain JUGAND, MD
    • Principal Investigator: Romain JUGAND, MD
  • Malataverne, France, 43200
    • EHPAD Les Cèdres Malataverne
    • Contact: Aurélie BUISSON, MD
    • Principal Investigator: Aurélie BUISSON
  • Saint-Etienne, France, 42055
    • CHU DE SAINT-ETIENNE
    • Sub-Investigator: Martin KILLIAN, MD
    • Contact: Baptiste GRAMONT, MD
    • Principal Investigator: Baptiste GRAMONT, MD
  • Saint-Just-Saint-Rambert, France, 42170
    • EHPAD La M.R.L
    • Contact: Anne PAVY, MD
    • Principal Investigator: Anne PAVY, MD
  • Saint-Étienne, France
    • EHPAD de la Talaudière, la Rivière, la Croix de l'Horme
    • Contact: Thomas CELARIER, PhD
    • Principal Investigator: Thomas CELARIER

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria :

• Patient affiliated or entitled to a social security scheme
• Residing in a Long-Term Care Unit (LTCU) or a Facility for the Elderly Dependent (EHPAD)
• A person deemed a priori, by the geriatrician member of the monitoring committee, to be capable of following the dietary recommendations required for the study.
• A person deemed a priori, by the clinician in charge, to be able to follow the dietary recommendations required by the study.
• Patient who has received informed information about the study and has co-signed a consent to participate in the study with the investigator.

Exclusion Criteria :

• Inability and/or unwillingness to follow dietary recommendations and/or perform follow-up examinations required for the study
• Iso-resource group 1 or 2 according to the AGGIR grid
• BMI < 18.5 kg/m2 or recent weight loss > 5% in 1 month or recent weight loss > 10% in 6 months from previous weight
• Albuminemia < 30g/l
• All swallowing disorders requiring a specific diet.
• Influenza vaccination received prior to inclusion
• Episode of influenza or suspected influenza during the 2020-2021 season and prior to inclusion
• Any acute medical or surgical event less than 2 weeks prior to inclusion
• Presence of systemic inflammatory or autoimmune disease
• Presence of an innate or acquired immune deficiency (including taking immunosuppressive treatment)
• Presence of a chronic disease which, according to the physician, makes the follow-up of a "fasting diet" and/or the consumption of large amounts of liquids (cf. fasting diet modalities) risky (e.g. insulin-dependent or insulin-requiring diabetes, severe heart failure, severe kidney failure, active cancer, significant undernutrition...) or impossible (e.g. advanced neurodegenerative pathology).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Fasting mimicking diet (FMD); patients aged 65 and over, institutionalized in Long Term Care Units (USLD) or Establishments for the elderly (EHPAD).

Dietary supplement: Fasting mimicking diet (FMD); D1 will correspond to a "pre-fasting" phase, with about 800 kcal of intake (approximately 40% of normal caloric intake) from a mono-nutrient diet (fruit, rice or potato according to the patient's preferences). Then D2 and D3 will correspond to the days of actual fasting, with 200-350 kcal of intake (10-18% of normal caloric intake) in the form of 100 ml of broth or vegetable juice (with a teaspoon of linseed oil) three times a day, and vaccination will take place on D4, after returning to a normal diet. 2 to 3 liter of water or unsweetened drink per day is required.Laxatives (unsweetened) will be prescribed and can be taken as during the fasting period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of premature discontinuation of the fasting-mimicking diet	measurement of the rate of occurrence of a clinical event considered to require discontinuation of the fasting diet : The occurrence of a clinical event considered to require discontinuation of the fasting diet will be defined as the presence between D14 and D21 of at least one of the following conditions: Weight loss > 5%,; Hypoglycemia < 0.5 g/l (< 2.8 mmol/l),; Hypothermia < 35°C,; Heart rate < 50 beats per minute, checked twice at 15 minute intervals,; Low systolic blood pressure < 90 mmHg or > 200 mmHg; or diastolic blood pressure < 60 mmHg or > 110 mmHg; or mean blood pressure < 70 mmHg, checked twice at 15-minute intervals,; Increase of 5 points on the visual analog pain scale between D14 and D21,; A score of 1 on the EVIBE visual analog scale (instantaneous assessment of well-being) between D14 and D21,; Any serious acute clinical event (fall with serious traumatic consequence, acute medical or surgical condition).	between Day 14 and Day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serious and non-serious adverse events reported	Comparison of the nature and frequency of serious and non-serious adverse events reported from D0 to D13 (pre fasting diet phase), D14 to D16 (fasting diet phase) and D17 to D42 (post fasting diet phase)	Between day 0 to day 42
composite outcome: evolution of biological biochemic parameters	Evolution of measurements of blood glucose, ketones, albumin, prealbumin and IGF-1 Unit of measure : ng/ml	Day 0 to Day 42
composite outcome: evolution of biological blood parameters	Evolution of the measurement of the blood total lymphocyte count (CD4, CD8, CD19, naive, effectors, memories, regulators, etc.). Unit of measure : %	Day 0 to Day 42
composite outcome: evolution biological inflammatory parameters	Evolution of inflammatory markers (CRP, IL1, IL6, TNFalpha) Unit of measure : ng/ml	Day 0 to Day 42

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Investigators: Principal Investigator: Baptiste GRAMONT, MD, Baptiste.Gramont@chu-st-etienne.fr

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: April 4, 2023
• First Submitted That Met QC Criteria: May 10, 2023
• First Posted (Actual): May 12, 2023

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: immunosenescence; tolerance; Aged; immunology; Fasting mimicking diet
• Other Study ID Numbers: 21CH028; 2023-A00390-45 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No