Clinical trial NCT03175601: Sleep Disturbances and Biomarkers of Sarcopenic OBesity
Official title: Sleep Disturbances and Biomarkers of Sarcopenic OBesity: Insight Into Mechanisms of Prefrailty
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Sarcopenic Obesity
Keywords: Sleep disturbances
Biomarkers
Prefrailty
Insulin resistance
Olfactory impairment
Multiplex array
Gait speed
Lead sponsor: Istituto di Fisiologia Clinica CNR
Sponsor class: OTHER
Collaborators: name: Niguarda Hospital
First posted: 2017-06-05
Enrollment: 100
Sex: ALL
Minimum age (years): 55
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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).

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Prevalence of prefrailty
timeFrame: Day one
Secondary outcomes:
measure: Prevalence of sarcopenia
timeFrame: Day one
measure: Cardiometabolic risk profile: insulin resistance
timeFrame: Day one
measure: Cardiometabolic risk profile: fatty liver
timeFrame: Day one
measure: Cardiometabolic risk profile: 10-year cardiovascular risk
timeFrame: Day one
measure: Sleep abnormalities: idiopathic REM Behaviour Disorder (iRBD)
timeFrame: Day one
measure: Sleep abnormalities: insomnia severity
timeFrame: Day one
measure: Sleep abnormalities: daytime sleepiness
timeFrame: Day one
measure: Cardiac rhythm abnormalities
timeFrame: Day one
measure: Cardiac dysautonomia: deep breathing test
timeFrame: Day one
measure: Cardiac dysautonomia: lying to standing test
timeFrame: Day one
measure: Orthostatic hypotension
timeFrame: Day one
measure: Olfactory function: Total Olfactory Score (TOS)
timeFrame: Day one
measure: Screening for cognitive impairment
timeFrame: Day one
measure: Tissue accumulation of Advanced Glycation End-products (AGE)
timeFrame: Day one
measure: Biomarkers of oxidative stress
timeFrame: Day one
measure: Inflammatory biomarkers
timeFrame: Day one
measure: Adipokines
timeFrame: Day one
measure: Myokines
timeFrame: Day one
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Istituto di Fisiologia Clinica del CNR UOS Milano
Study officials:
affiliation: Istituto di Fisiologia Clinica CNR
name: Maria Giovanna Trivella, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Istituto di Fisiologia Clinica CNR
name: Jonica Campolo, MSc
role: STUDY_DIRECTOR
References: