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

Patrizia D'Amelio

Status: Not yet enrolling

Conditions: Malnutrition; Sarcopenia

Treatments: Dietary Supplement: Micronutriments; Dietary Supplement: BCAA; Dietary Supplement: standard treatment + placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05324475

MIMOSA

Details and patient eligibility

About

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.

Full 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 ®, nestle) and nutritional counselling (SC).

SC-Placebo: These patients will receive ONS and maltodextrin 4 g BCAAs: 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, as delivered in our previous study. Micronutrient complements (Micro). In addition to the ONS the patients will receive a combination of micronutrients.

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 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.

Enrollment: 240 estimated patients

Sex: All

Ages: 75+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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240 participants in 3 patient groups, including a placebo group

Standard treatment (SC)

Placebo Comparator group

Description:

nutritional counselling (SC) + Placebo: These patients will receive Oral Nutrient Supplementation (ONS) and maltodextrin 4 g

Treatment:

Dietary Supplement: standard treatment + placebo

Branch-chained aminoacids

Experimental group

Description:

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.

Treatment:

Dietary Supplement: BCAA

Micronutrients

Experimental group

Description:

In addition to the ONS the patients will receive a combination of micronutrients

Treatment:

Dietary Supplement: Micronutriments