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

Sarcopenia Clinical Trial

— MIMOSA  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05324475
• Other study ID #: MIMOSA
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2024
• Source: Centre Hospitalier Universitaire Vaudois
• Contact: Patrizia D'amelio
• Phone: +41213143712
• Email: patrizia.damelio[@]chuv.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 240
• Est. completion date: December 31, 2026
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 75 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Malnutrition
• Sarcopenia

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
Switzerland	Patrizia D'amelio	Lausanne

Sponsors (1)

Lead Sponsor	Collaborator
Patrizia D'Amelio

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	change in perceived health status (score)	questionnaire	change versus baseline at rehab discarge (21 days), 30, 60 days after discharge