Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02718586 |
| Other study ID # |
104074 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
March 4, 2016 |
| Last updated |
February 15, 2017 |
| Start date |
March 2016 |
| Est. completion date |
December 2016 |
Study information
| Verified date |
February 2017 |
| Source |
Tungs’ Taichung Metroharbour Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The aim is to test if serum level of myokines are associated with protein energy wasting,
inflammation and atherosclerotic vascular disease among Taiwanese dialysis patients. Some
novel myokines levels, anthropometric parameters, cardiovascular risk factors, and presence
of endothelial dysfunction will be examined in 250 subjects. The distribution of some
recently identified myokines such as irisin, myotatin etc levels will be studied and
correlated markers of malnutrition, endothelial dysfunction, inflammation and insulin
resistance. In the present study, the investigators will further follow and investigate
whether serum myokines levels are associated with long-term mortality from all causes and
from cardiovascular disease.
Description:
Study Design and Population
In this study, patients who underwent stable hemodialysis at least 3 months at Tung Taichung
Metroharbor Hospital will be enrolled. Baseline clinical data such as age, sex, height,
bodyweight , clinical etiology of Chronic kidney disease(CKD) if possible, comorbidities,
blood pressure, laboratory measures [such as serum creatinine, albumin, C-reactive protein
(CRP), total cholesterol, complete blood counts, urine routines, anthropometric information
and various potential indicators of protein energy wasting [such as body mass index,
waist/hip ratio, mid-arm circumference (MAC), triceps skinfold thickness (TSF), mid-arm
muscle circumference (MAMC), mid-arm muscle area (MAMA), SGA, BIS analyses, dual energy
x-ray absorptiometry(DEXA),handgrip (HG)] will be collected. For the laboratory tests,
fasting blood and urine samples are obtained from each patient and performed by means of
routine methods in the investigators hospital. All patients received echocardiograms studies
performed within 3 months after enrollment, which were used to estimate congestive heart
failure(CHF, defined as an ejection fraction of <50%) or left ventricular hypertrophy (LVH,
defined as left ventricle mass index >125 g/m2 in men and 100 g/m2 in women).Cardiovascular
disease( CVD) was defined as a previous history of CHF, LVH, ischemic heart
disease(including prior history of angina, myocardial infarction, coronary artery bypass
grafting and percutaneous cardiac catheter intervention) or cerebrovascular disease
(including prior history of transient ischemic attack and stroke). Information about
conventional clinical risk factors, such as smoking, diabetes mellitus, hypertension,
medication and other necessary data at baseline will be obtained from a standardized
interview and examination. The diagnosis of type 2 diabetes is made according to the
criteria of the American Diabetes Association.
Patients with malignant disease, acute infectious disease, inflammatory disease (such as
collagen disease), advanced liver disease, and those taking any type of immunosuppressive
medication were also excluded. Patients with clinical manifestations of atherosclerosis,
congestive heart failure, history of stroke, a previous history of coronary intervention or
coronary artery bypass graft surgery, and presence peripheral vascular disease were
recorded.
Anthropometrics, and Handgrip Strength
Body weight was measured with light clothing on up to 0.1 kg. Height was measured up to 0.1
cm. Waist circumference was measured at the midpoint between upper iliac and lower costal
level up to 0.1 cm at the end of normal expiration. Hip circumference was measured around
the largest part of the hip. Anthropometric measurements were obtained immediately after the
HD session by a trained researcher. Body mass index (BMI) was calculated as body mass
divided by stature squared. The International Society of Renal Nutrition and
Metabolism(ISRNM) panel recommends that a BMI lower than 23 kg/m2 is a marker of Protein
Energy Wasting(PEW). Anthropometric measurements include TSF used skinfold calipers; MAC
measured by a stretchable measuring tape, MAMC equals MAC(centimeter) - 3.14 x TSF
(millimeter)/10 and MAMA equals (MAMC2/4π). Muscle mass area (MMA) was calculated using the
following equation: MMA = ([MAC {cm} - π x triceps skinfold {cm}]2/4π) -n, where n = 10 for
men and 6.5 for women . Muscle strength as hand grip strength (HGS) test was measured by
Hand Dynamometer. HGS was measured 3 times for both left and right hands with patients in a
standing position using a dynamometer in units of kilograms. Patients held the dynamometer
at thigh level and were encouraged to squeeze the instrument as hard as possible for 3 s.
The maximum grip strength among all measurements was used for this study. Three sets of
measurements at each site were averaged and used in the analyses.
Malnutrition Inflammation Score
To assess the malnutrition-inflammation complex syndrome(MICS), also known as the Kalantar
score, developed, and validated by Kalantar- Zadeh et al. was measured at baseline. The
Malnutrition-Inflammation Score(MIS) has ten components [change in end dialysis dry weight,
dietary intake, gastrointestinal symptoms, functional capacity, comorbidities, decreased fat
stores or loss of subcutaneous fat (according to SGA), signs of muscle wasting (according to
SGA), BMI, serum albumin, and total iron binding capacity], each with four levels of
severity, from 0 (normal) to 3 (severely abnormal). The sum of the MIS components ranges
from 0 (normal) to 30 (severely malnourished), in which a higher score reflects greater
malnutrition and inflammation severity.
The comorbidity component was scored as 0 if no comorbidities were present; 1 if there were
mild comorbidities present and major comorbid conditions (MCCs) were absent (such as New
York Heart Association Class III or IV congestive heart failure, severe coronary artery
disease, acquired immunodeficiency syndrome, moderate- to-severe chronic obstructive
pulmonary disease, and metastatic malignancies); 2 if moderate comorbidities were present,
including one MCC; and 3 if multiple severe comorbidities were present, including two or
more MCCs. Subjective global assessments (SGAs) were performed by an experienced physician
according to conventional SGA guidelines.
Dual-energy X-ray absorptiometry
Whole-body scans are performed according to manufacturer's instructions, and body fat, lean
tissue mass (LTM) and bone mineral content (BMC) are analysed using the manufacturer's
software. DEXA estimate of fat-free mass (FFM) was calculated as a sum of LTM and BMC
estimates. All patients were examined by the same observer.
Bioelectric impedance spectroscopy (BIS)
BIS measurement was performed in each of the participants enrolled in the study by a
specific member of staff who had completed a training course in the BIS technique, using a
portable whole body bioimpedance spectroscopy device, the body composition monitor. The body
composition monitor(BCM) measures the impedance spectroscopy at 50 different frequencies
between 5 kilohertz(kHz) and 1 megahertz (MHz). Measurements were taken on the midweek
dialysis session before the start of the hemodialysis treatment with the patient calm,
supine, and relaxed in the dialysis bed for 10 minutes. Specific exclusion criteria were
dictated by the device and included history of a pacemaker, defibrillator, metallic sutures,
or stent implantation and amputation of a major limb.
Biochemical Analysis
Blood samples were taken in a nonfasting state before a midweek hemodialysis session.
Complete blood count, creatinine, urea, albumin, transferrin, total carbon dioxide, hsCRP ,
triglycerides (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C),
low-density lipoprotein-cholesterol (LDL-C), and fasting blood glucose are measured by
routine laboratory methods. Another blood samples will be stored at -80 degree centigrade
for subsequent assay of items such as insulin, interleukin-6, pentraxin, nitrotyrosine for
markers of endothelial dysfunction such as Asymmetric dimethylarginine( ADMA), adropin and
insulin resistance (adiponectin, resistin and leptin). Homeostatic Model Assessment Insulin
Resistance(HOMA-IR) was calculated as fasting insulin (U/l) × fasting glucose (mg/dl)/405,
as described by Matthews et al.
Serum total p-cresol and indoxyl sulfate (i.e. combined free and protein-bound fractions)
were analyzed with High-performance liquid chromatography (HPLC). Briefly, serum samples
were deproteinized for the determination of indoxyl sulfate by the addition of three parts
methanol to one part serum. Total p-cresol (i.e. the combined free and protein-bound
fraction) was analysed after deproteinization (acid and heat) and extraction (ethyl acetate)
of serum samples.
Measurement of serum myostatin, irisin and myonectin
Serum myostatin levels are measured with a competitive immunoassay kits according to the
manufacturer's protocol. Serum irisin concentration was measured using the enzymelinked
immunosorbent assay). The assay was proven to be highly sensitive to human irisin. Serum
myonectin (Circulating Complement-C1q Tumor necrosis factor(TNF)-Related Protein 15) Serum
myonectin was determined with a commercially available enzyme-linked immunosorbent assay
kit.
