Sleep Disturbances and Biomarkers of Sarcopenic OBesity (SleSOB)

Sleep Disturbances and Biomarkers of Sarcopenic OBesity: Insight Into Mechanisms of Prefrailty

The general objective of this study is to identify biomarkers of sleep quality, sarcopenia, insulin resistance, oxidative stress and inflammation associated with prefrailty in middle-aged and elderly obese subjects through the integrated study of sleep patterns, functional cardiovascular testing, olfactory function and circulating molecules.

Results from the SleSOB study will contribute to identify molecular and functional determinants of prefrailty, to allow early targeted interventions and will have important implications for empowerment of elderly citizens to self-management of preventive measures and healthy lifestyle.

Study Overview

• Status: Unknown
• Conditions: Sarcopenic Obesity

Detailed Description

Frailty, an age-related state of low physiological reserve and high vulnerability to stressors, impacts on health, functional independence, quality of life and survival; its early detection at the prefrailty stage offers the opportunity for preventive intervention. Sarcopenia, a hallmark of frailty, may occur in association with obesity and worsen functional deterioration. Obesity is strongly associated with insulin resistance and is a risk factor for both cardiometabolic diseases and cognitive impairment. Adipose tissue exerts autocrine and paracrine functions leading to chronic low-grade inflammation and increased oxidative stress that, in turn, decrease muscle density and precipitate muscle strength loss. Sleep disturbances and sarcopenia might be causally related through dysregulation of glucose metabolism and disruption of the secretory pattern of hormones involved in muscle metabolism.

Main objective:

To establish among young-elderly obese subjects the prevalence of prefrailty as defined by presence of ≥1 of reduced muscle mass, fatigue, weakness, slowness, and low physical activity (Fried's criteria)

Secondary objectives:

• To assess prevalence and severity of sarcopenia as defined by reduced muscle mass coupled with decreased muscle strength and /or reduced functional capacity
• To establish the cardiometabolic risk profile and its correlation with vitamin D
• To determine type and extent of sleep abnormalities by validated questionnaires and their association with prefrailty
• To assess the extent of sympathetic imbalance, arrhythmia burden and olfactory impairment
• To determine patterns of biomarkers of oxidative stress, inflammatory cytokines, adipokines, myokines, tissue damage and remodeling and correlation with prefrailty and insulin resistance.

Study design:

Eligible subjects will attend the clinic in the morning in the fasting state to undergo

• blood samples collection for routine and specific biochemistry;
• anthropometric measurements: height, weight, body mass index, waist and hip circumference;
• assement of sarcopenia: muscle strength, gait speed, muscle mass by biomimpedentiometric assessment (BIA) and air displacement pletismography (BODPOD);
• glucose metabolism biomarker as tissue accumulation of advanced glycation endproducts (AGE);
• sympathetic activation;
• interview for medical history and comorbidity registration;
• screening for cognitive impairment;
• sleep pattern analysis through questionnaires;
• olfactory assessment.

A wearable system (Win@home, CE0434) for 24 h recording of rhythm, circadian heart rate, respiratory rate and oxygen saturation, posture and physical activity will be applied to each subject for the subsequent 24 hours

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Renata De Maria, MD; Phone Number: +390266101344; Email: renata.demaria@ospedaleniguarda.it
• Study Contact Backup: Name: Jonica Campolo, MSc; Phone Number: +39026473407; Email: jonica.campolo@ospedaleniguarda.it

Study Locations

• Italy
  • Milano, Italy, 20162
    • Istituto di Fisiologia Clinica del CNR UOS Milano

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Middle-aged and young-old obese subjects will be enrolled at a specialised nutrition clinic. Subjects will be on a maintenance weight management program including lifestyle advice and diet based on the principles of the Modern Mediterranean Diet Pyramid (variety in food choices, seasonality and spices to flavor dishes). The diet is modified to avoid high caloric food and distributed in 3 main meals and 2 healthy snacks during the day to provide a caloric intake of 28-30 kcal/die/kg body weight and macronutrient breakdown as recommended by INRAN (http://www.inran.it/) (Protein 15%, Fat < 30%, carbohydrates 55/60% of which soluble 10-12 % and fiber 30 g die).

Description

Inclusion Criteria:

• Obesity : body mass index ≥ 30 and <40 kg/m2
• Written informed consent

Exclusion Criteria:

• Diabetes requiring insulin treatment
• Stage IV chronic kidney dysfunction (estimated glomerular filtration rate <15 ml/min)
• Liver dysfunction (AST- ALT x 2 times upper normalcy range)
• Active neoplasms
• Claustrophobia
• Psychiatric morbidity or any other condition that impairs the ability to give informed consent

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of prefrailty	Proportion of subjects presenting with one or more of reduced muscle mass, fatigue, weakness, slowness, and low physical activity	Day one

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of sarcopenia	Proportion of subjects presenting with reduced muscle mass (by gender-specific cut offs ) coupled with decreased muscle strength (men ≤ 32 kg, women ≤ 21 kg and/or reduced gait speed (<0.8 mt/sec on a 4 mt course)	Day one
Cardiometabolic risk profile: insulin resistance	Homeostatic Model Assessmenti (HOMA)-insulin resistance index	Day one
Cardiometabolic risk profile: fatty liver	Fatty liver index (FLI)	Day one
Cardiometabolic risk profile: 10-year cardiovascular risk	HeartSCORE	Day one
Sleep abnormalities: idiopathic REM Behaviour Disorder (iRBD)	Answer to screening question for iRBD	Day one
Sleep abnormalities: insomnia severity	Insomnia Severity Index (ISI) score	Day one
Sleep abnormalities: daytime sleepiness	Epworth Sleepiness Scale (ESS) score	Day one
Cardiac rhythm abnormalities	Atrial fibrillation burden during 24 hour home monitoring	Day one
Cardiac dysautonomia: deep breathing test	Expiratory/inspiratory ratio	Day one
Cardiac dysautonomia: lying to standing test	Lying-to standing ratio	Day one
Orthostatic hypotension	Drop ≥20 mmHg in systolic and/or ≥10 mmHg in diastolic blood pressure after 1 and 5 minutes of active standing	Day one
Olfactory function: Total Olfactory Score (TOS)	Sum of Olfactory Threshold, Identification, Discrimination scores	Day one
Screening for cognitive impairment	Mini Mental State Examination (MMSE) score	Day one
Tissue accumulation of Advanced Glycation End-products (AGE)	AGE Reader Score	Day one
Biomarkers of oxidative stress	Malondyaldehyde, aminothiols	Day one
Inflammatory biomarkers	Cytokinesinterleukin-6, interleukin-1beta, tumour ecrosis Factor-alpha, neopterin	Day one
Adipokines	Adiponectin, leptin	Day one
Myokines	Myostatin, irisin	Day one

Collaborators and Investigators

• Sponsor: Istituto di Fisiologia Clinica CNR
• Collaborators: Niguarda Hospital
• Investigators: Principal Investigator: Maria Giovanna Trivella, MD, Istituto di Fisiologia Clinica CNR; Study Director: Jonica Campolo, MSc, Istituto di Fisiologia Clinica CNR

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2017
• Primary Completion (Anticipated): May 1, 2018
• Study Completion (Anticipated): July 1, 2018

Study Registration Dates

• First Submitted: June 1, 2017
• First Submitted That Met QC Criteria: June 1, 2017
• First Posted (Actual): June 5, 2017

Study Record Updates

• Last Update Posted (Actual): June 6, 2017
• Last Update Submitted That Met QC Criteria: June 2, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Insulin resistance; Biomarkers; Sleep disturbances; Gait speed; Prefrailty; Olfactory impairment; Multiplex array
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Wake Disorders; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Dyssomnias; Parasomnias
• Other Study ID Numbers: 422-102016

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