Ignite Creation Date:
2024-05-05 @ 11:55 PM
Last Modification Date:
2024-10-26 @ 10:41 AM
Study NCT ID:
NCT01448174
Status:
COMPLETED
Last Update Posted:
2014-10-07
First Post:
2011-10-05
Brief Title:
Salusin-alpha - a New Factor in the Pathogenesis of Lipid Abnormalities in Hemodialysis Patients
Sponsor:
Poznan University of Medical Sciences
Organization:
Poznan University of Medical Sciences
Study Overview
Official Title:
Salusin-alpha - a New Factor in the Pathogenesis of Lipid Abnormalities in Hemodialysis Patients
Status:
COMPLETED
Status Verified Date:
2014-10
Last Known Status:
None
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:
Hyperlipidemia and atherosclerosis lead to cardiovascular diseases and are an indirect cause of increased death rate in the general population This association is still more evident in specific subpopulations like patients with advanced chronic kidney disease CKD especially hemodialysis HD patients due to a higher prevalence of lipid disturbances and atherosclerosis compared to the general population Cardiovascular events in CKD patients are frequently associated with traditional risk factors including diabetes male sex hypertension dyslipidemia and advanced age However these factors failed to fully account for the increased risk of cardiovascular events in CKD The efforts are made to identify new risk factors that contribute to the development of atherosclerosis and participate in causes of cardiovascular death In 2003 there were identified peptides designated salusin-alpha and salusin-beta Development of atherosclerosis may be suppressed by salusin-alpha Salusin-alpha may have a lipid lowering effect similar to that of statins
The purpose of this study is to investigate whether 1 salusin-alpha is associated with lipid metabolism of HD patients without or with metabolic syndrome or type 2 diabetes mellitus similarly or not like in healthy or obese subjects 2 treatment with atorvastatin and its effects are associated with changes in plasma salusin-alpha concentration if so - whether it is dependent on the direct influence of atorvastatin on salusin-alpha or associated with a decrease in serum lipid level 3 salusin-alpha may predict mortality in HD patients
The purpose of this study is to investigate whether 1 salusin-alpha is associated with lipid metabolism of HD patients without or with metabolic syndrome or type 2 diabetes mellitus similarly or not like in healthy or obese subjects 2 treatment with atorvastatin and its effects are associated with changes in plasma salusin-alpha concentration if so - whether it is dependent on the direct influence of atorvastatin on salusin-alpha or associated with a decrease in serum lipid level 3 salusin-alpha may predict mortality in HD patients
Detailed Description:
Purpose I step 1 To investigate whether plasma salusin-alpha is associated with lipid and lipid-related abnormalities in hemodialysis HD patients plasma salusin-alpha concentration expression of receptor CD36 on macrophages serum lipid parameters anthropometric and laboratory indices of nutrition and biomarkers of inflammation will be cross-sectionally analyzed In chronic kidney disease CKD patients there is a close association between atherosclerosis A malnutrition M and inflammation I known as MIA syndrome so interactions between all these parameters will be obviously present and should be taken into account In addition homeostasis model assessment of insulin resistance HOMA-IR will be applied as insulin resistance is a metabolic abnormality occurring in advanced CKD in metabolic syndrome shown in about 50 of HD patients and diabetic mellitus DM being a cause of CKD in approximately 40 of cases Results of correlations and associations shown in HD patients will be compared with those of healthy controls and obese persons with normal renal function for evaluation of salusin-alpha relationships under different metabolic conditions which may exert not uniform influence
Study populations
HD patients n 200 Obese persons n 50 Controls n 60
Data collection
Medical history with special attention for demographics - age gender cause of CKD renal replacement therapy vintage changes in body weight habits and data required for inclusion and exclusion criteria
Physical examination with special attention for skin abnormalities related to lipid disturbances and blood pressure
Anthropometric indices
directly measured height body weight hip and waist circumferences midarm circumference MAC triceps skin fold thickness TSF
calculated or estimated hip to waist ratio WHiR height to waist ratio WHeR body mass index BMI in HD patients - dry body weight DBW Laboratory parameters
Apolipoprotein A1 APOA1
Apolipoprotein B APO B
Cholesterol - total
Cholesterol HDL
Cholesterol LDL directly measured
CD36
Free fatty acids FDA
High sensitivity C-reactive protein hsCRP
HOMA-IR
Interleukin 6 IL-6
L-carnitine
Lipase
Lipoproteina
Salusin-alpha
Triglycerides
Basic serum biochemistry
Purpose I step 2 HD patients suffering from type 2DM or having metabolic syndrome MeS are at risk of more severe lipid abnormalities than the remaining ones Data collected in Step 1 will be helpful in diagnosis of MeS in the examined HD patients The investigators expect that also in controls they will find persons with abnormal serum lipid profile Differences inside these both groups may influence plasma salusin-alpha levels and the examined associations Thereby the following groups will be analyzed separately and compared to each other
For HD patients
group with MeS and with type 2 DM
group only with MeS
group only with type 2 DM
group without MeS and without DM
For controls
group without detected serum lipid abnormalities
group with detected serum lipid abnormalities
Validation of correlationsassociations found in the cross-sectional study will be done in the prospective studies Purpose II and at the final analysis Purpose III
Purpose II The treatment with atorvastatin lowers serum LDL cholesterol in HD patients Using this statin during the study the investigators can observe dynamic changes in serum LDL cholesterol in HD patients with known plasma salusin-alpha concentration before atorvastatin medication With repeated salusin-alpha measurements during continued atorvastatin treatment the investigators can follow concomitantly occurring or not occurring changes in plasma salusin-alpha concentrations which can be related to atorvastatin directly or to its LDL cholesterol lowering effect To elucidate this aspect the investigators plan to examine hyperlipidemic HD patients treated with a prescribed diet and increased physical activity as well as obese persons not taking lipid lowering medication during weight lowering therapy which usually decreases lipidemia Results of these persons may give the answer whether a decrease in lipidemia without pharmaceutical medication leads may be also leads to changes in plasma salusin-alpha concentration
The prospective study is planned in two groups of persons
HD patients participating in Step 1 n 200 Obese persons participating in Step 1 n 50
Purpose III Annual mortality rate in HD patients is 10 - 15 LDL cholesterol and total cholesterol are predictors of mortality in end-stage renal disease patients If salusin-alpha is associated with lipid abnormalities it is a reasonable to check whether this peptide may be a predictor of mortality in HD patients To investigate this aspect the investigators plan to perform the analysis of HD patients outcome after two years from the first salusin-alpha determination and to check whether there is any association between plasma salusin-alpha concentration and death from cardiovascular events and all cause death
Study populations
HD patients n 200 Obese persons n 50 Controls n 60
Data collection
Medical history with special attention for demographics - age gender cause of CKD renal replacement therapy vintage changes in body weight habits and data required for inclusion and exclusion criteria
Physical examination with special attention for skin abnormalities related to lipid disturbances and blood pressure
Anthropometric indices
directly measured height body weight hip and waist circumferences midarm circumference MAC triceps skin fold thickness TSF
calculated or estimated hip to waist ratio WHiR height to waist ratio WHeR body mass index BMI in HD patients - dry body weight DBW Laboratory parameters
Apolipoprotein A1 APOA1
Apolipoprotein B APO B
Cholesterol - total
Cholesterol HDL
Cholesterol LDL directly measured
CD36
Free fatty acids FDA
High sensitivity C-reactive protein hsCRP
HOMA-IR
Interleukin 6 IL-6
L-carnitine
Lipase
Lipoproteina
Salusin-alpha
Triglycerides
Basic serum biochemistry
Purpose I step 2 HD patients suffering from type 2DM or having metabolic syndrome MeS are at risk of more severe lipid abnormalities than the remaining ones Data collected in Step 1 will be helpful in diagnosis of MeS in the examined HD patients The investigators expect that also in controls they will find persons with abnormal serum lipid profile Differences inside these both groups may influence plasma salusin-alpha levels and the examined associations Thereby the following groups will be analyzed separately and compared to each other
For HD patients
group with MeS and with type 2 DM
group only with MeS
group only with type 2 DM
group without MeS and without DM
For controls
group without detected serum lipid abnormalities
group with detected serum lipid abnormalities
Validation of correlationsassociations found in the cross-sectional study will be done in the prospective studies Purpose II and at the final analysis Purpose III
Purpose II The treatment with atorvastatin lowers serum LDL cholesterol in HD patients Using this statin during the study the investigators can observe dynamic changes in serum LDL cholesterol in HD patients with known plasma salusin-alpha concentration before atorvastatin medication With repeated salusin-alpha measurements during continued atorvastatin treatment the investigators can follow concomitantly occurring or not occurring changes in plasma salusin-alpha concentrations which can be related to atorvastatin directly or to its LDL cholesterol lowering effect To elucidate this aspect the investigators plan to examine hyperlipidemic HD patients treated with a prescribed diet and increased physical activity as well as obese persons not taking lipid lowering medication during weight lowering therapy which usually decreases lipidemia Results of these persons may give the answer whether a decrease in lipidemia without pharmaceutical medication leads may be also leads to changes in plasma salusin-alpha concentration
The prospective study is planned in two groups of persons
HD patients participating in Step 1 n 200 Obese persons participating in Step 1 n 50
Purpose III Annual mortality rate in HD patients is 10 - 15 LDL cholesterol and total cholesterol are predictors of mortality in end-stage renal disease patients If salusin-alpha is associated with lipid abnormalities it is a reasonable to check whether this peptide may be a predictor of mortality in HD patients To investigate this aspect the investigators plan to perform the analysis of HD patients outcome after two years from the first salusin-alpha determination and to check whether there is any association between plasma salusin-alpha concentration and death from cardiovascular events and all cause death
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None