Leucine Supplementation in Sarcopenic Older Individuals

Beneficial Effect of Leucine Supplementation in Muscular, Functional and Cognitive Functions in Sarcopenic Older Individuals

Caring with older people in west societies has becoming a challenge for all health professional and any measure that can increase health or well-being will be ultimately improve quality of life and life expectancy. Frailty is a geriatric syndrome describing physical and functional decline that occurs as a consequence of certain diseases (e.g., cancer, chronic infection, etc.) but also even without disease. Frailty is characterized by an increased risk for poor outcomes such as incident falls, fractures, disability, comorbidity, health care expenditure and premature mortality. The aetiology of frailty is not well understood but it has been associated with changes in several physiologic systems, including inflammation, metabolic and micronutrients deficits.

The investigators wish to test with a confident perspective that any measured that improve the efficiency of muscular system can prevent the progression of frailty syndrome and that can have many others effects since it has been consistently demonstrated that a proper muscular function in aging is associated with other signs and symptoms. Looking at the literature, there are two clinical trials that evaluated the effect of leucine supplementation in older individuals with beneficial effects. The investigators wish to replicate those findings and to extend the analysis of the effect afforded by leucine supplementation in sarcopenia, frailty and cognitive function in individuals living in nursing homes in Valencia and province. This trial will show the eventual effects of leucine supplementation in elderly people may be also useful to afford some beneficial effects (sleep, cognitive function, depressed mood, balance and gait, etc) by modulating the function of muscular and metabolic system and in reduce the progression of sarcopenia and loss of muscular function.

Study Overview

• Status: Completed
• Conditions: Frail Elderly Syndrome; Sarcopenia
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Leucine

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Valencia, Spain
    • University of Valencia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability to walk alone or with help of a can or a walker
• Age 60 years or older
• Cognitive function equal or higher than 21points in Mini-mental examination score
• Both genders
• Institutionalized in nursing homes for at least 6 months

Exclusion Criteria:

• Clinical diagnosed severe dementia
• Severe psychiatric disease (i.e. schizophrenia)
• Glomerular filtrate <30 ml/min/1,73m2

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Group; Subjects in control group will receive placebo (lactose) 6g/day in two doses, in two spoon at noon (12 pm) and in the late afternoon (8 pm) for 13 weeks. The product will be delivered in powder, in white jars, without label, and will only carry the patient number on the outside, 4 jars per participant.	Dietary supplement: Placebo; Administration 6 g/day of lactose at noon (12 pm) and in the late afternoon (8 pm) for 13 weeks
Active Comparator: Intervention Group; Subjects in intervention group will receive leucine 6g/day, in tin two doses, in two spoon at noon (12 pm) and in the late afternoon (8 pm) for 13 weeks. The product will be delivered in powder, in white jars, without label, and will only carry the patient number on the outside, 4 jars per participant.	Dietary supplement: Leucine; Administration 6 g/day of leucine at noon (12 pm) and in the late afternoon (8 pm) for 13 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lean mass	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated according to European Group of Working Sarcopenia in older people criteria: Skeletal muscle mass index (kg/m2)	4 months
Strength	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated according to European Group of Working Sarcopenia in older people criteria: Handgrip Strength (kg)	4 months
Physical performance	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated according to European Group of Working Sarcopenia in older people criteria: Walking speed (m/s)	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cholesterol	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated with a blood analysis to determine total, HDL and LDL cholesterol (mg/dL)	4 months
Glucose	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated with a blood analysis to determine glucose (mg/dL)	4 months
Creatinine	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated with a blood analysis to determine creatinine (mg/dL)	4 months
Triglycerides	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated with a blood analysis to determine triglycerides (mg/dL)	4 months
IL-6	Before starting and after finishing administration of Leucine supplement or placebo, metabolic biomarkers related to sarcopenia and muscular function of all participants will be evaluated as: IL6 (pg/mL)	4 months
TNF-alfa	Before starting and after finishing administration of Leucine supplement or placebo, metabolic biomarkers related to sarcopenia and muscular function of all participants will be evaluated as: TNF-alfa (pg/mL)	4 months
IGF-1	Before starting and after finishing administration of Leucine supplement or placebo, metabolic biomarkers related to sarcopenia and muscular function of all participants will be evaluated as: IGF-1 (mg/mL)	4 months
Leucine	Before starting and after finishing administration of Leucine supplement or placebo, metabolic biomarkers related to sarcopenia and muscular function of all participants will be evaluated as leucine concentration (mg/mL)	4 months
Valine	Before starting and after finishing administration of Leucine supplement or placebo, metabolic biomarkers related to sarcopenia and muscular function of all participants will be evaluated as valine concentration (mg/mL)	4 months
Isoleucine	Before starting and after finishing administration of Leucine supplement or placebo, metabolic biomarkers related to sarcopenia and muscular function of all participants will be evaluated as isoleucine concentration (mg/mL)	4 months
Glutamine	Before starting and after finishing administration of Leucine supplement or placebo, metabolic biomarkers related to sarcopenia and muscular function of all participants will be evaluated as glutamine concentration (mg/mL)	4 months
B-alanine	Before starting and after finishing administration of Leucine supplement or placebo, metabolic biomarkers related to sarcopenia and muscular function of all participants will be evaluated as B-alanine concentration (mg/mL)	4 months
Albumine	Before starting and after finishing administration of Leucine supplement or placebo, metabolic biomarkers related to sarcopenia and muscular function of all participants will be evaluated as: albumine (g/L)	4 months
Transthyretin	Before starting and after finishing administration of Leucine supplement or placebo, metabolic biomarkers related to sarcopenia and muscular function of all participants will be evaluated as: transthyretin (mg/L)	4 months
Myostatin	Before starting and after finishing administration of Leucine supplement or placebo, metabolic biomarkers related to sarcopenia and muscular function of all participants will be evaluated as: myostatin (ng/mL)	4 months
Body mass index	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated as: Body mass index (kg/m2)	4 months
Body perimeters	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated as: Abdominal and calf perimeter (cm)	4 months
Body composition	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated as bioimpedance to know fat and lean mass (kg)	4 months
Comorbidities	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated as Charlson index score (absence of comorbidity: 0-1 points, low comorbidity: 2 points, and high comorbidity > 3 points)	4 months
Type and number of drugs used	Before starting and after finishing administration of Leucine supplement or placebo, the drugs consumed by each participant will be collected	4 months
Gait and balance	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated with Tinetti index Scale(0 to 28 points, 19-24 risk of falling, <19 high risk of falling)	4 months
Basic activities of daily living	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated with Barthel index Scale to measure the activities of daily living and mobility (o to 100 points, < 60 dependence)	4 months
Cognitive performance	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated with Mini-mental score examination Scale (MMSE - 0 to 30 points, <24 points cognitive impairment, <21 mild cognitive impairment)	4 months
Depression	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated with Yesavage Scale for geriatric depression (0 to 15 points, >5 points high risk of depression)	4 months
Forced spirometry	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated as forced spirometry parameters (measured with a spirometer)	4 months
Respiratory muscles strenght	Before starting and after finishing administration of Leucine supplement or placebo, all participants will be evaluated as maximal respiratory pressures (measured with a respiratory pressure gauge)	4 months

Collaborators and Investigators

• Sponsor: University of Valencia
• Collaborators: Armonea Group - La Saleta; Bonusan BV
• Investigators: Principal Investigator: Omar Cauli, MD, PhD, Universitat de València

Publications and helpful links

General Publications

• Martinez-Arnau FM, Fonfria-Vivas R, Buigues C, Castillo Y, Molina P, Hoogland AJ, van Doesburg F, Pruimboom L, Fernandez-Garrido J, Cauli O. Effects of Leucine Administration in Sarcopenia: A Randomized and Placebo-controlled Clinical Trial. Nutrients. 2020 Mar 27;12(4):932. doi: 10.3390/nu12040932.

Helpful Links

• Link to the main article published in Nutrients, March 2020

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Actual): October 1, 2019
• Study Completion (Actual): October 14, 2019

Study Registration Dates

• First Submitted: November 9, 2018
• First Submitted That Met QC Criteria: February 4, 2019
• First Posted (Actual): February 5, 2019

Study Record Updates

• Last Update Posted (Actual): April 6, 2020
• Last Update Submitted That Met QC Criteria: April 2, 2020
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Sarcopenia; Frailty; Aged; Leucine
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Sarcopenia
• Other Study ID Numbers: H1524420647893

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No data will be shared with other researchers

Drug and device information, study documents

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