Multicomponent Analysis of phYsical Frailty BiomarkErs: Focus on Mitochondrial Health - MAYBE (MAYBE)

The study will be conducted in a group of obese sarcopenic patients (Sarco-Ob) aged > 60 years on moderately hypocaloric diet therapy aimed at comparing the effect of a strength exercise protocol, combined or not with dietary supplementation with amino acids, on physical performance, muscle strength, body composition, muscle oxidative metabolism, and biomarkers of sarcopenia. The supplementation study will be conducted in a double-blind manner.

Study Overview

• Status: Completed
• Conditions: Frailty; Sarcopenic Obesity; Malnutrition; Protein
• Intervention / Treatment: Behavioral: Placebo; Behavioral: Exe-H; Dietary supplement: AA-1; Dietary supplement: AA-2

Detailed Description

In this double-blind randomised control trial, older men, and women resident in Verona (Italy) will be selected from the Geriatrics Nutritional Clinic of the Borgo Trento Hospital or were contacted by telephone. A specific medical screening was initially programmed to verify the criteria of recruitment.

Anthropometric and body composition In the morning, in a fasted state, body mass will be taken with an electronic scale (Tanita electronic scale BWB-800 MA) and stature will be measured with a Harpenden stadiometer (Holtain Ltd., Crymych, Pembs. UK); BMI will be calculated as weight (kg)/height (m)2. Thereafter, total and regional body composition will be evaluated by means of dual-energy X-ray absorptiometry (DXA) using a total body scanner (QDR Horizon W, Hologic, MA, USA; fan-bean technology, software for Windows XP version 12.4.2) according to the manufacturer's procedures. Furthermore, the ALMI will be calculated as the sum of lean mass of arms and legs divided by height squared.

Physical performance On the same day, the SPPB test will be used to assess functional performance of the lower extremities. Each participant will performed: 4 m at usual customary gait speed, a five repeated chair-stands test and three standing balance tests (side by side, semi-tandem and tandem).

A digital dynamometer (CAMRY, Digital Hand Dynamometer model: EH101) will be used to assess HGS and all measurements were conducted by the same operator. Before starting, participants will observe a demonstration of the test procedure and engage in two practice attempts.

Knee muscle strength measurements and analysis An isokinetic dynamometer (CMSi Cybex Humac Norm Dynamometer, Lumex, Ronkokoma, NY, USA) will be used to assess the isokinetic strength of knee flexors and extensors muscles.

Maximal isokinetic knee extension-flexion tests will be performed in a randomised sequence at 60, 90, 150, 180 and 210°ˑs-1. Trials will consist in three knee extension-flexion movements with 60 s-recovery. The maximal strength of knee extensors muscle will be calculated with the Hill's hyperbolic function. The isokinetic knee extension-flexion power will be calculated as the product between strength and velocity. Finally, for knee extensors, maximal muscle power expressed in Watt, will be calculated from the power-velocity curve.

1-RM assessment Before starting training intervention, participants will perform three sessions of familiarization with the resistance isotonic machines. High intensity strength exercise (Exe-H) protocol: All the participants will performed a supervised progressive resistance training protocol, three times per week, 1 hour per session. Each participant will performed the same strength training protocol, starting with 3 sets of 8-10 repetitions at 70% of 1-RM (month 1), with a progressive increase of intensity at 75% of 1-RM (month 2 and month 3), and 80% 1-RM that will be maintained for the rest period of intervention. The compliance will be define as the number of exercise sessions expressed in % of the target value. Each participant will must reach a compliance above the 70% to be included in the final analysis.

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Verona, Italy, 37126
    • AOUI Verona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Participants will be included in the study based on the following inclusion criteria:

• Older men and women between 60-80 years
• The presence of sarcopenic obesity was considered when the following two conditions were satisfied: Fat mass > 34.8% and FFM <90% of subject's ideal FFM.
• Resident in Verona (Italy)
• Stable weight in the previous 2 months
• Previously sedentary (less than one hour of exercise per week in the last 6 months)
• Signing of the informed consent for participation in the study

Exclusion criteria:

• Unstable angina or recent myocardial infarction
• Malignant or unstable arrhythmias
• Heart failure NYHA class > II
• Severe respiratory failure
• Severe heart valve disease (i.e severe aortic stenosis or insufficiency)
• Abdominal and/or thoracic aneurysm
• Recent intracerebral or subdural haemorrhage
• Poorly controlled arterial hypertension
• Presence of pacemakers or metal prostheses
• Severe chronic renal failure
• Symptomatic musculoskeletal pathology
• Symptomatic disc herniation, arthrosis, acute joint, tendon and ligamentous injuries, hip and/or knee prostheses recently placed (<6 months) or with joint instability, symptomatic or large inguinal or abdominal hernia
• Acute retinal detachment or bleeding
• Recent eye surgery (laser, cataract, retinal surgery, glaucoma surgery)
• History of malignant cancer within the previous 5 years
• Diagnosis of dementia
• Eating disorders

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exe-H + placebo; high intensity physical exercise combined with placebo	Behavioral: Placebo; Nutritional Placebo; Behavioral: Exe-H; high intensity physical exercise
Experimental: Exe-H + AA-1; high intensity physical exercise combined with low dose of aminoacids	Behavioral: Exe-H; high intensity physical exercise; Dietary supplement: AA-1; low dose aminoacids
Experimental: Exe-H + AA-2; high intensity physical exercise combined with high dose of aminoacids	Behavioral: Exe-H; high intensity physical exercise; Dietary supplement: AA-2; high dose aminoacids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline 1-repetition maximum with isokinetic dynamometer at 5-months	Change in 1-repetition maximum test performed with isokinetic dynamometer in Kilograms	Month0, Month5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline Short Physical Performance Battery at 5-months	Change in Short Physical Performance Battery Score	Month0, Month 5
Change from baseline in handgrip at 5-months	Change in upper limb muscle strength measured with handgrip in kilograms	Month0, Month5
Changesfrom baseline skeletal muscle mass at 5-months	Change skeletal muscle mass measured with DXA in kilograms	Month0, Month5
Change from baseline fat mass at 5-months	Change fat mass measured with DXA in kilograms	Month0, Month5
Change from baseline in mRNA at 5-months	Change mRNA dosage	Month0, Month5
Change from baseline in muscle power at 5-months	Change in isokinetic muscle power of the lower limbs in kilograms	Month0, Month5

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Universitaria Integrata Verona
• Collaborators: Azienda Ospedaliera di Padova; University of Milan; Università degli Studi di Brescia
• Investigators: Study Director: Elena Zoico, PhD, Universita di Verona

Publications and helpful links

Helpful Links

• Healthy Aging Center Verona web site

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Actual): July 6, 2022
• Study Completion (Actual): July 6, 2022

Study Registration Dates

• First Submitted: February 21, 2020
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 10, 2023

Study Record Updates

• Last Update Posted (Actual): July 10, 2023
• Last Update Submitted That Met QC Criteria: July 3, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nutrition Disorders; Severe Acute Malnutrition; Frailty; Malnutrition; Kwashiorkor
• Other Study ID Numbers: 1956CESC

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