Maintaining Immune and Mitochondrial Functions in Old Adults With SAfe Nutrition. (MIMOSA)

Maintaining Immune and Mitochondrial Functions in Old Adults With SAfe Nutrition: the MIMOSA Study.

Aging is associated with an increased inflammation named "inflammageing" and with an altered immune response. Different mechanisms have been proposed to explain the phenomenon of inflammageing and increased oxidative stress: deficiencies in essential amino acids, and some micronutrients have an important impact and may induce immune cell dysregulation. Mitochondrial dysfunction may explain the complex relationship between malnutrition sarcopenia, immune dysfunction and aging.

Therefore, a personalized nutritional strategy aiming to improve mitochondrial function, decrease oxidative stress, down-regulate inflammation and restore immunity appears to be a logical approach in order to treat malnutrition and its biological and clinical consequences.

MIMOSA will investigate the role of nutritional supplements in rescuing altered mitochondrial function and redox state imbalance.

Study Overview

• Status: Recruiting
• Conditions: Malnutrition; Sarcopenia
• Intervention / Treatment: Dietary supplement: standard treatment + placebo; Dietary supplement: BCAA; Dietary supplement: Micronutriments

Detailed Description

The study participants will all receive optimal standard care ensuring the optimal protein and energy intakes, with at least 1 g protein per kg body weight and day, and 30 kcal per kg body weight and day (or the measured energy expenditure (EE) value). This will be realized by the daily administration of oral nutritional supplements (ONS) providing whole proteins together with dietary advice [according with the ESPEN nutrition guidelines. All the patients will receive the standard commercially available product used at CHUV (Resource protein ®, Nestlé) and nutritional counselling (SC).

All participants included in this study will receive daily, the oral nutritional supplement (ONS), one sachet and two capsule (for blinding purpose).

The intervention nutrients will be delivered as follows:

• BCAA: 1 sachet containing 4 g of BCAA (details in Table 1)
• Micronutrients: 1 sachet containing 4 g of the micronutrient blend and 2 capsules containing 0.6 g of OMEGA 3 PUFA (details in table 1).

The placebos will be delivered like this:

-1 sachet containing 1 g of maltodextrin and 2 capsules containing 0.6 g of coconut oil. (detailed in Table 1).

The duration of the intervention will be 6 weeks, but at least 4 weeks After enrollment patients will be subjected to evaluation of muscle mass by bioimpedance (BIA), muscle strength will be by handgrip strength and muscle performance by the Short Performance Physical Battery (SPPB).

Nutritional status will be evaluated by the Mini Nutritional Assessment short form (MNA-SF), Nutrition Risk screening (NRS) score and Body mass index (BMI). Energy expenditure (EE) will be measured by indirect calorimetry using a canopy.

Moreover appropriate experiments will be carried out in order to evaluate mitochondrial bioenergetics, replication, and fusion, as well as of redox state.

Analyses of inflammageing and immune-senescence will be done by appropriate lab experiments.

Micronutrient status will be measured by ELISA or HPLC and ICPMS respectively. Patients will be evaluated at inclusion, at rehabilitation discharge, and one and two months after rehabilitation discharge. The volume of blood required for the above investigations will be 3 x 30 ml over the 2-month period.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Patrizia D'amelio; Phone Number: +41213143712; Email: Patrizia.DAmelio@chuv.ch

Study Locations

• Switzerland
  • Lausanne, Switzerland, 1012
    • Recruiting
    • CHUV
    • Contact: Patrizia D'amelio; Phone Number: +41213143712; Email: Patrizia.DAmelio@chuv.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥75 years
• Patients entering a rehabilitation program
• Diagnosis of malnutrition defined by a MNA-SF (mini-nutritional assessment short form) score below 11 points.
• Commitment to accept the nutritional supplement proposed, willing and able to give written informed consent
• Ability to understand and comply with the requirements of the study

Exclusion Criteria:

• Presence of malignancy,
• Life expectancy of less than two months calculated by Multidimensional Prognostic Index (MPI ),
• Congestive heart failure (NYHA IV),
• Chronic renal disease (creatinine clearance <40 ml/min calculated by cockroft),
• Liver cirrhosis (Child B-C),
• Tube/percutaneous endoscopic gastrostomy feeding or parenteral nutrition,
• Severe dysphagia,
• Mini-Mental State Examination (MMSE)≤18 and MNA>11 points. MMSE ≥ 18 identifies patients with mild form of cognitive impairment; those patients generally do not have problems in swallowing and are able to take drugs.
• Severe anaemia (Hb<10 g/l) or leukopenia (<2G/l).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Standard treatment (SC); nutritional counselling (SC) + Placebo: These patients will receive Oral Nutrient Supplementation (ONS) and maltodextrin 4 g	Dietary supplement: standard treatment + placebo; daily administration of oral nutritional supplements (ONS) 1) providing whole proteins together with dietary advice according with the ESPEN nutrition guidelines. All the patients will receive the standard commercially available product used at CHUV (Resource protein ®, nestle ) and nutritional counselling (SC) and maltodextrin 4 g as placebo
Experimental: Branch-chained aminoacids; In addition to the ONS these patients will receive 4 gram per day of BCAAs mixture. Ratio between the BCAAs will be Leucine/Isoleucine/Valine=2:1:1.	Dietary supplement: BCAA; daily administration of oral nutritional supplements (ONS) 1) providing whole proteins together with dietary advice according with the ESPEN nutrition guidelines. All the patients will receive the standard commercially available product used at CHUV (Resource protein ®, nestle) and nutritional counselling (SC) and 4 gram per day of BCAAs mixture. Ratio between the BCAAs will be Leucine/Isoleucine/Valine=2:1:1
Experimental: Micronutrients; In addition to the ONS the patients will receive a combination of micronutrients and PUFA	Dietary supplement: Micronutriments; daily administration of oral nutritional supplements (ONS) 1) providing whole proteins together with dietary advice according with the ESPEN nutrition guidelines. All the patients will receive the standard commercially available product used at CHUV (Resource protein ®, nestle ) and nutritional counselling (SC) and Vitamin A 1200 mg RE, Vitamin D3 2000 IU, Thiamine B1 100 mg, Cobalamin B12 10 mcg, Ascorbic acid C 200 mg, Iron 30 mg, Selenium 100 mcg, Zinc 20 mg, Omega-3 PUFA 1 g

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mitochondrial ATP production (nmol/ml)	Production of ATP will be measured using the ATP Bioluminescent Assay Kit	change vesus baseline at 30, 60 days after discharge
Change in redox state (plasmatic concentration of metabolites)	analyses of thiometabolome contains: methionine, methionine sulfone, methionine sulfoxide, cysteine, homocysteine, homocystine, cystathionine, formylmethionine, cystine, glutathione, glutathione disulfide, taurine, S-adenosylmethionine, S-adenosylhomocysteine, N-acetylcysteine, cysteic acid, serine, glycine, glutamic acid, lypoic acid, selenocysteine, thioctic acid, pyruvic acid.	change vesus baseline at 30, 60 days after discharge
Change in mitochondrial electron flux (nmol cit/min/mg prot)	The activity of Complex I and III will be measured on non-sonicated mitochondrial samples	change vesus baseline at 30, 60 days after discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change micronutrients status (concentration of micronutrients)	Blood levels of Vitamins A, B12, D and E, as well as of trace elements Cu, Fe, Se, and Zn will be determined by ELISA or HPLC and ICPMS	change versus baseline at 60 days after discharge
change in inflammation	Production of pro-inflammatory cytokines involved in inflammageing and in muscle waste will be measured by ELISA technique; we will measure IL-6 and TNF-alpha (pg/ml).	change versus baseline at 30, 60 days after discharge
change phase angle (score)	Bioelectrical impedance analysis (BIA) will be carried out	change versus baseline at rehab discarge (21 days), 30, 60 days after discharge
muscle function (score)	Short performance physical battery will be used to measure muscle performance	change versus baseline at rehab discarge (21 days), 30, 60 days after discharge
muscle mass (Kg/body weight)	Bioelectrical impedance analysis (BIA) will be used to measure muscle mass	change versus baseline at rehab discarge (21 days), 30, 60 days after discharge
muscle strength (Kg)	Hand grip will be used to measure muscle strenght	change versus baseline at rehab discarge (21 days), 30, 60 days after discharge
change in perceived health status (score)	questionnaire	change versus baseline at rehab discarge (21 days), 30, 60 days after discharge

Collaborators and Investigators

• Sponsor: Patrizia D'Amelio
• Investigators: Principal Investigator: Patrizia D'amelio, Service de gériatrie et réadaptation gériatrique-CHUV

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): March 30, 2028

Study Registration Dates

• First Submitted: March 25, 2022
• First Submitted That Met QC Criteria: April 5, 2022
• First Posted (Actual): April 12, 2022

Study Record Updates

• Last Update Posted (Actual): May 31, 2025
• Last Update Submitted That Met QC Criteria: May 28, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: nutrition; micronutrients; sarcopenia; malnutrition; immune system; Mitochondria; oxydative stress; inflammaegeing; branch-chained aminoacids
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neuromuscular Manifestations; Nutrition Disorders; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Malnutrition; Sarcopenia
• Other Study ID Numbers: MIMOSA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The data will be shared according to the F.A.I.R. principles as follows. Findable- Accessible. All data collected will be uploaded to the Redcap research data repository after anonymization.

Interoperable. The majority of the raw data produced will be in standard formats for which there is suitable open source software available.

Reusable. Data publicly available will use the Creative Commons Attribution version 3.0 (http://creativecommons.org/licenses/by/3.0/) license that permits free sharing and adaptation of the licensed data with the restrictions depicted above and any related scientific publications as well as documenting any changes. Each dataset will contain appropriate citation details in the accompanying README file.

We will make data open immediately if not sensitive for IP protection. Data with sensitive IP will be made available after 5 years from the end of the project,

• IPD Sharing Time Frame: We will make data open immediately if not sensitive for IP protection. Data with sensitive IP will be made available after 5 years from the end of the project
• IPD Sharing Access Criteria: upon reasonable request to the PI
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No