Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04309201 |
| Other study ID # |
108084 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 10, 2020 |
| Est. completion date |
December 31, 2020 |
Study information
| Verified date |
January 2021 |
| Source |
Tungs' Taichung Metroharbour Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Insulin resistance (IR) is an early metabolic alteration in chronic kidney disease (CKD)
patients, becoming almost universal in those who reach the end stage of kidney failure. The
skeletal muscle represents the primary site of IR in CKD, and alterations at sites beyond the
insulin receptor are recognized as the main defect underlying IR in this condition. The
etiology of IR in CKD is multifactorial in nature and may be secondary to disturbances that
are prominent in renal diseases, including physical inactivity, chronic inflammation,
oxidative stress, vitamin D deficiency, metabolic acidosis, anemia, adipokine derangement,
and altered gut microbiome.
IR has been solidly associated with intermediate mechanisms leading to cardiovascular (CV)
disease in CKD including left ventricular hypertrophy, vascular dysfunction, and
atherosclerosis. Recent studies have identified a muscle factor β-aminoisobutyric acid
(BAIBA), which is produced by skeletal muscle during physical activity. BAIBA have been found
to link with sedentary life style, abdominal obesity, and impairments in carbohydrate and
lipid metabolism. A few studies have shown that BAIBA can protect from diet-induced obesity
in animal models. It induces transition of white adipose tissue to a "beige" phenotype, which
induces fatty acids oxidation and increases insulin sensitivity. While the exact mechanisms
of BAIBA-induced metabolic effects are still not well understood, the aim of this study is
want to study its relationship with muscle wasting and insulin resistance in a group of
non-diabetic hemodialysis patients.
Description:
Study Design and Population
Patients and Methods
This study is an observational, cross-sectional and prospective cohort study. One hundred and
fifty patients on non-diabetic hemodialysed patients will be included for the cross-sectional
survey; Twenty healthy subjects will be elected as the controls. Prevalent adult HD patients
with dialysis vintages over 3 months will be recruited. Patients are maintained on regular HD
prescription, three times a week, for four-hour sessions. Subjects with significant comorbid
conditions such as cancer, heart failure, or severe liver disease and chronic infection such
diabetic foot will be excluded. This study is conducted according to the guidelines laid down
in the Declaration of Helsinki, and all procedures were reviewed as well as approved by the
Regional Hospital Ethics Committee. All subjects should give their written informed consent
to participate in the study. Subjects' demographic and clinical characteristics, including
age, gender, weight, height, body mass index (BMI), dialysis vintage, and Kt/V will be
recorded, and comorbidities and current therapies will be collected.
Anthropometric and biochemical assessments
Systolic and diastolic blood pressures are taken with the subjects in the supine position. A
measurement of height and weight was performed on all subjects. Waist circumference was
measured at the midpoint between the lower border of the rib cage and the iliac bone. The
concentration of plasma insulin was assayed by radioimmunoassay. Fasting plasma glucose was
measured using the glucose oxidase method. HbA1c was measured by affinity chromatography.
Total cholesterol, triglyceride, and HDL cholesterol levels were measured enzymatically using
an autoanalyzer (Hitachi 747; Hitachi, Tokyo, Japan). Serum insulin concentrations are
determined by IRMA. Adiponectin and leptin concentrations are measured using a commercially
available ELISA kit.
Sample preparation
In each subject, the blood samples are drawn from the arteriovenous fistula in of each
participant in the morning after fasting for at least 8 h and on the day of hemodialysis. The
samples are properly processed, refrigerated at 2-8 C, and the plasma is separated
immediately by centrifugation. Each serum sample is heat-inactivated by incubation at 65 C
for 30 min. Fetal bovine serum (FBS; Gibco BRL, Grand Island, NY, USA), a negative control,
is treated with activated charcoal (Sigma, St. Louis, MO, USA) overnight at 4 C and filtered
to remove all small molecules and AhR agonists that might have been present. TCDD, a positive
control for AhR agonists, was purchased from Sigma Co. Plasma BAIBA levels are assessed by a
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, as previously described
(15). Cell-based AhR ligand activity (CALA) assay and ELISA assay will be performed (16)
HOMA-IR, HOMA-%B, HOMA-%S, and disposition index are calculated by the following formulae.
HOMA-IR1 = [fasting insulin (mU/l) × fasting glucose(mg/dl)× 0.0555]/22.5 HOMA-%B1 = [20 ×
fasting insulin (mU/l)]/[(fasting glucose(mg/dl) × 0.0555)-3.5] HOMA-%S1 = [1/ HOMA-IR1] ×
100% Disposition index 1= (HOMA-%S1/100) × (HOMA-%B1/100)
Dual-Energy X-ray Absorptiometry (DEXA)
DEXA is a widely used reference method for body FFM and FM measurements.(10) DEXA was
performed using a Lunar Prodigy (GE Medical Systems, Madison, WI). Whole-body scans were
performed according to manufacturer's instructions, and body FM (FMDEXA), LTM (LTMDEXA) and
bone mineral content were analyzed using the manufacturer's software. The DEXA method uses an
X-ray tube with a filter to generate low-energy (40 kV) and high-energy (70 or 100 kV)
photons. When photons at different energy levels pass through tissue, their absorptions can
be expressed as a ratio of attenuation at lower or higher energy levels. DEXA estimate of FFM
was calculated as a sum of LTMand bone mineral content estimates. All patients were examined
by the same observer.
Bioelectric Impedance Spectroscopy
Whole-body bioelectric impedance spectroscopy (BIS) measurement using a body composition
monitor (BCM: Fresenius Medical Care, Bad Homburg, Germany) was performed on each of the
participants enrolled in the study by a specific member of the staff who had completed a
training course in the BCM technique. The BCM measures the impedance spectroscopy at 50
different frequencies between 5 kHz and 1 MHz. Measurements were taken on the day before
dialysis with the patient calm, supine, and relaxed in the dialysis bed for 10minutes. Four
electrodes were placed on the patient's hand and foot on the side contra lateral to their
arteriovenous fistula. 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. As a multifrequency bioimpedance device, BCM not only provides extracellular
(ECWBCM), intracellular (ICWBCM), and total body water (TBWBCM) measurements but also
estimates the body composition in terms of lean tissue mass (LTMBCM-mainly muscle), fat mass
(FATBCM), adipose tissue mass (ATMBCM-mainly fat), and overhydration (OH) according to the
body compositionmodel.(17) This device combined BIS with the BCM model described in Chamney
et al,11 and it takes into account the dissimilar hydration of relevant tissues. Briefly, the
device was modified to reflect the presence of excess fluid accumulated due to pathologic
reasons, that is, patients with kidney failure. It has therefore set constants for each of
the body composition compartment. This device has been shown to be as precise as the gold
standardreference methods and has been validated against reference methods for volume status
and body composition assessments in healthy and HD populations, with methods frequently used
in the 4-compartment model. The percentage proportions of LTMBCM, FATBCM, andATMBCM were
denoted accordingly as pLTMBCM, pFATBCM, and pATMBCM.
Muscle Strength
The muscle function will be assessed on the same day of the recruitment immediately before
starting the HD session by handgrip strength measurement, using a handle dynamometer. The
test is performed conducting three attempts with each hand, and the mean of the strongest
hand is used to determine muscle strength
