Ignite Creation Date:
2024-05-06 @ 3:26 PM
Last Modification Date:
2024-10-26 @ 1:49 PM
Study NCT ID:
NCT04630132
Status:
UNKNOWN
Last Update Posted:
2020-12-11
First Post:
2020-11-10
Brief Title:
Renal Ageing-sarcopenia Network
Sponsor:
IRCCS San Raffaele
Organization:
IRCCS San Raffaele
Study Overview
Official Title:
Renal Ageing-sarcopenia Network a Combined Genetic Immunological and Psychological Approach to Dissect Frailty
Status:
UNKNOWN
Status Verified Date:
2020-12
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Frailty is a syndrome in which the accumulation of small individually insignificant deficits leads to heightened vulnerability to adverse events and predisposes to potential catastrophic decompensation
Objective of this study is to clarify the underlying genetic and immunological mechanisms responsible of frailty condition focused on i nephrosclerosis ageing kidney phenotype related to salt effects on immunosystem ii immunological aspect of sarcopenia iii psychological disorder related to immunosystem activation iv detection of new biomarkers of frailty
Objective of this study is to clarify the underlying genetic and immunological mechanisms responsible of frailty condition focused on i nephrosclerosis ageing kidney phenotype related to salt effects on immunosystem ii immunological aspect of sarcopenia iii psychological disorder related to immunosystem activation iv detection of new biomarkers of frailty
Detailed Description:
The cross-sectional observational cohort study include 1500 subjects age 65 years subdivided in 750 cases and 750 controls according to frailty
Subjects who met the following criteria are included 1 older than 65 2 able to walk 500 m without assistance 3 a Mini-Mental State Examination MMSE score 18 and 4 no severe health problems eg uncontrolled hypertension recent upper or lower extremity fractures myocardial infarction within the past 1 year
According to definition for the phenotype of frailty cases is as follows presence of three or more of the following features
1 Decreased grip strength
2 Self-reported exhaustion
3 Unintentional weight loss of more than 45 kg over the past year
4 Slow walking speed
5 Low physical activity
The investigators select as control subjects with presence of less than 1 criteria All the control subjects are evaluated by the same protocol than the cases Subjects will be collected in collaboration with senior housing RSA of Milano city country clubs social club for elderly and elderly university The study will be approved by the Ethics Committee of ASL of Milano city and at individual centers by local ethical committees All the study participants signed informed consent At the baseline evaluation a large amount of data is collected First the participants completed a battery of self-reported questionnaires concerning the demographic characteristics psychosocial adjustment quality of life and health condition in the presence of a trained psychologist in order to clarify any doubts Second an expert in physical education and adapted physical activity for older adults administered physical tests Finally people with expertise in the eld of ergonomics take anthropometric measurements Data collection is always carried out in the same order and individually for each participant
In all the subjects following clinical and laboratoristic data are collected
1 Clinical evaluation
1 Collection of anamnestic data
2 Blood pressure measurement Blood pressure is measured by a trained nurse using an authomatic device OMRON and an appropriately sized cuff Readings are obtained after 5 min of seated rest The mean of 3 blood pressure measurements obtained at 1-min intervals during the medical evaluation is used to define SBP and DBP
3 Evaluation of kidney function
a CKD is defined as a glomerular filtration rate GFR lower than 60 mLmin173 m2 or markers of kidney damage such as albuminuriafor greater than 3 months A creatinine-based formula is used to estimate GFR applying Chronic Kidney Disease Epidemiology Collaboration CKD-EPI equations
b Urine analysis and albumin creatinine and sodium creatinine ratio urinary excretion
2 Physical frailty measure To identify physically frail older adults an adapted version of the frailty phenotype of Fried et al is used Subjects with three or more criteria are classified as frail those with one or two as prefrail and those meeting none as robust
1 Body composition Height and weight are detected Bioimpedance analysis BIA is a system of evaluation of body composition able to calculate adjunctive information total body water TBW extra and intracellular water ECW and ICW body cell mass BCM muscle mass MM fat mass FM fat free mass FFM basal metabolic rate
2 SPPB The short physical performance battery SPPB is a group of measures that combines the results of the gait speed chair stand and balance tests It has been used as a predictive tool for possible disability and can aid in the monitoring of function in older people The scores range from 0 worst performance to 12 best performance
3 PASE Physical Activity Scale for the Elderly PASE is a brief 5 minutes and easily scored survey designed specifically to assess physical activity in epidemiological studies of persons age 65 years and older The PASE score combines information on leisure household and occupational activity The PASE assesses the types of activities typically chosen by older adults walking recreational activities exercise housework yard work and caring for others It uses frequency duration and intensity level of activity over the previous week to assign a score ranging from 0 to 793 with higher scores indicating greater physical activity
Sarcopenia will be defined as fat-free mass index FFMI below the 25th percentile combined with one of the following functional parameter either an SPPB score 8 or a comfortable gait speed 10 ms
3 Psychological test will be used to assess self conditions
1 Mini Mental State Examination MMSE The Mini-Mental Stat Examination MMSE is a 10-minute measure of cognitive impairment in undeveloped uneducated diseased or very old populations
2 Geriatric Depression Scale-short form GDS-15 The Geriatric Depression Scale GDS is a 15- item self-report validated measure for rating depression in elderly adults Additionally the GDS is sensitive to depression among elderly adults suffering from mild to moderate dementia and elderly adults with physical illnesses by excluding questions pertaining to somatic complaints and cognitive dimension of depression In this scale a score of 6 or higher may be indicative of depression and must be evaluated jointly with patients clinical data
3 SF-36 Medical Outcomes Study MOS 36-item Short Form Health Survey This instrument should capture both mental and physical aspects of health The 36 6-likert item assess health across eight domains namely bodily pain general health perceptions mental health physical functioning role limitations due to emotional health problems role limitations due to physical health problems social functioning and vitality All items use categorical response options range 2-6 options Two component summary scores for physical and mental health MPS and MCS respectively can also be calculated
4 Laboratory Methods
1 Genotyping OpenArray technology ThermoFisher for genetic characterization of Single Nucleotide Polymorphisms SNPs based on TaqMan chemistry DNA will be used for genotyping of genetic variants in loci for Klotho KL gene Adducins ADD1 ADD2 and ADD3 and EO synthesis LSS HSD3B1 metabolism CYP11A1 ABCB1 and activity SLC8A1 SIK1 genes and for immunological pathway TLR4 HMGB1 IL6 IL1
2 Biochemical measurements
1 Endogenous Ouabain measurement
2 Plasma Klotho measurement
3 Immunological determinations Simultaneous assessment of serum concentrations of epidermal growth factor EGF fibroblast growth factor 2 FGF2 FMS-like tyrosine kinase 3 ligand Flt-3L granulocyte colony-stimulating factor G-CSF granulocyte-monocyte colonystimulating factor GM-CSF interferon-α2 IFN-α2 INF-γ IL-10 IL-15 IL-17 IL-1β IL-2 IL-6 IL-8 INF-γ inducible protein 10 IP-10 monocyte chemoattractant protein-1 MCP-1 macrophage inflammatory protein-1β MIP-1 β platelet-derived growth factor-AA PDGF-AA soluble CD40 ligand sCD40L transforming growth factor alpha TGF-α TNF-α and vascular endothelial growth factor VEGF
Subjects who met the following criteria are included 1 older than 65 2 able to walk 500 m without assistance 3 a Mini-Mental State Examination MMSE score 18 and 4 no severe health problems eg uncontrolled hypertension recent upper or lower extremity fractures myocardial infarction within the past 1 year
According to definition for the phenotype of frailty cases is as follows presence of three or more of the following features
1 Decreased grip strength
2 Self-reported exhaustion
3 Unintentional weight loss of more than 45 kg over the past year
4 Slow walking speed
5 Low physical activity
The investigators select as control subjects with presence of less than 1 criteria All the control subjects are evaluated by the same protocol than the cases Subjects will be collected in collaboration with senior housing RSA of Milano city country clubs social club for elderly and elderly university The study will be approved by the Ethics Committee of ASL of Milano city and at individual centers by local ethical committees All the study participants signed informed consent At the baseline evaluation a large amount of data is collected First the participants completed a battery of self-reported questionnaires concerning the demographic characteristics psychosocial adjustment quality of life and health condition in the presence of a trained psychologist in order to clarify any doubts Second an expert in physical education and adapted physical activity for older adults administered physical tests Finally people with expertise in the eld of ergonomics take anthropometric measurements Data collection is always carried out in the same order and individually for each participant
In all the subjects following clinical and laboratoristic data are collected
1 Clinical evaluation
1 Collection of anamnestic data
2 Blood pressure measurement Blood pressure is measured by a trained nurse using an authomatic device OMRON and an appropriately sized cuff Readings are obtained after 5 min of seated rest The mean of 3 blood pressure measurements obtained at 1-min intervals during the medical evaluation is used to define SBP and DBP
3 Evaluation of kidney function
a CKD is defined as a glomerular filtration rate GFR lower than 60 mLmin173 m2 or markers of kidney damage such as albuminuriafor greater than 3 months A creatinine-based formula is used to estimate GFR applying Chronic Kidney Disease Epidemiology Collaboration CKD-EPI equations
b Urine analysis and albumin creatinine and sodium creatinine ratio urinary excretion
2 Physical frailty measure To identify physically frail older adults an adapted version of the frailty phenotype of Fried et al is used Subjects with three or more criteria are classified as frail those with one or two as prefrail and those meeting none as robust
1 Body composition Height and weight are detected Bioimpedance analysis BIA is a system of evaluation of body composition able to calculate adjunctive information total body water TBW extra and intracellular water ECW and ICW body cell mass BCM muscle mass MM fat mass FM fat free mass FFM basal metabolic rate
2 SPPB The short physical performance battery SPPB is a group of measures that combines the results of the gait speed chair stand and balance tests It has been used as a predictive tool for possible disability and can aid in the monitoring of function in older people The scores range from 0 worst performance to 12 best performance
3 PASE Physical Activity Scale for the Elderly PASE is a brief 5 minutes and easily scored survey designed specifically to assess physical activity in epidemiological studies of persons age 65 years and older The PASE score combines information on leisure household and occupational activity The PASE assesses the types of activities typically chosen by older adults walking recreational activities exercise housework yard work and caring for others It uses frequency duration and intensity level of activity over the previous week to assign a score ranging from 0 to 793 with higher scores indicating greater physical activity
Sarcopenia will be defined as fat-free mass index FFMI below the 25th percentile combined with one of the following functional parameter either an SPPB score 8 or a comfortable gait speed 10 ms
3 Psychological test will be used to assess self conditions
1 Mini Mental State Examination MMSE The Mini-Mental Stat Examination MMSE is a 10-minute measure of cognitive impairment in undeveloped uneducated diseased or very old populations
2 Geriatric Depression Scale-short form GDS-15 The Geriatric Depression Scale GDS is a 15- item self-report validated measure for rating depression in elderly adults Additionally the GDS is sensitive to depression among elderly adults suffering from mild to moderate dementia and elderly adults with physical illnesses by excluding questions pertaining to somatic complaints and cognitive dimension of depression In this scale a score of 6 or higher may be indicative of depression and must be evaluated jointly with patients clinical data
3 SF-36 Medical Outcomes Study MOS 36-item Short Form Health Survey This instrument should capture both mental and physical aspects of health The 36 6-likert item assess health across eight domains namely bodily pain general health perceptions mental health physical functioning role limitations due to emotional health problems role limitations due to physical health problems social functioning and vitality All items use categorical response options range 2-6 options Two component summary scores for physical and mental health MPS and MCS respectively can also be calculated
4 Laboratory Methods
1 Genotyping OpenArray technology ThermoFisher for genetic characterization of Single Nucleotide Polymorphisms SNPs based on TaqMan chemistry DNA will be used for genotyping of genetic variants in loci for Klotho KL gene Adducins ADD1 ADD2 and ADD3 and EO synthesis LSS HSD3B1 metabolism CYP11A1 ABCB1 and activity SLC8A1 SIK1 genes and for immunological pathway TLR4 HMGB1 IL6 IL1
2 Biochemical measurements
1 Endogenous Ouabain measurement
2 Plasma Klotho measurement
3 Immunological determinations Simultaneous assessment of serum concentrations of epidermal growth factor EGF fibroblast growth factor 2 FGF2 FMS-like tyrosine kinase 3 ligand Flt-3L granulocyte colony-stimulating factor G-CSF granulocyte-monocyte colonystimulating factor GM-CSF interferon-α2 IFN-α2 INF-γ IL-10 IL-15 IL-17 IL-1β IL-2 IL-6 IL-8 INF-γ inducible protein 10 IP-10 monocyte chemoattractant protein-1 MCP-1 macrophage inflammatory protein-1β MIP-1 β platelet-derived growth factor-AA PDGF-AA soluble CD40 ligand sCD40L transforming growth factor alpha TGF-α TNF-α and vascular endothelial growth factor VEGF
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None