Salusin-alpha - a New Factor in the Pathogenesis of Lipid Abnormalities in Hemodialysis Patients

NCT01448174 | Completed Phase 4

• 1 other identifier: ALGN-001
• Study Type: interventional
• Target: 310
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Failure Chronic Requiring Hemodialysis; Metabolic Syndrome; Diabetes Mellitus Type 2; Hyperlipidemia

Keywords

salusin-alpha; atorvastatin; CD36; Hemodialysis

Outcome Measures

Primary Outcomes (1)

• normalization of serum LDL cholesterol

  30 weeks

Study Arms (3)

atorvastatin

ACTIVE COMPARATOR

The prospective, randomized, double-blind, placebo-controlled study: * will be preceded by one month non-pharmacological treatment of hyperlipidemia (prerandomization phase) * 130 hyperlipidemic hemodialysis (HD) patients will be randomly assigned to receive blinded study drug: 65 patients will be allocated to start with atorvastatin and 65 patients - with placebo. Atorvastatin will be administered and monitored according to the K/DOQI guidelines (2003). The prospective, observational study: \- 35 hyperlipidemic patients will be followed for 30 weeks on the prescribed non-pharmacological treatment of hyperlipidemia

Drug: Atorvastatin

Lifestyle counseling

NO INTERVENTION

Protocol of the prospective study in obese persons: * after taking the anthropometric measurements and collecting a blood sample, the start of weight lowering therapy with a prescribed diet and planned physical activity * follow-up for 30 weeks (measurement of body weight every week).

The controls (healthy volunteers)

NO INTERVENTION

Interventions

Atorvastatin DRUG

Atorvastatin (10 - 80 mg/day) will be administered orally in the one evening dose in the case of strict indications for such a treatment. Before starting atorvastatin, serum lipid profile will be examined two times, and when both results are abnormal the treatment is started. Duration of administration: * atorvastatin 12 weeks, 6 weeks washout, placebo 12 weeks or * placebo 12 weeks,6 weeks washout,atorvastatin 12 weeks.

Also known as: ATC: C 10 AA 05

atorvastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For HD patients:
• HD vintage at least 3 months
• signed consent for participation in the study
• For obese persons:
• BMI \> 30 kg/m2
• eGFR \> 60 ml/min/1.73 m2 BSA
• interest in weight loss according to weight loss diet protocol (WLDP)
• signed consent for participation in the study
• For controls (healthy volunteers):
• declared health, comfort
• no substantial changes in the medical interview and physical examination
• no medication
• signed consent for participation in the study

You may not qualify if:

• For HD patients:
• active thyroid gland disease and/or thyreotropic medication
• treatment with corticosteroids, immunosuppressants or hormones
• treatment with statins or fibrates in 6 weeks before the study commencement
• diagnosis of genetic lipid abnormalities
• neoplastic disease
• acute coronary syndrome and/or cerebral stroke in 6 months before the study commencement
• surgery in 3 months before the study commencement
• plasma activities of ALT and/or AST exceeding 3 times the upper laboratory normal limit
• non compensated diabetes mellitus
• For obese persons:
• a known history of moderate or severe cardiovascular disease, stroke or transient ischemic attack
• uncontrolled hypertension
• severe dyslipidemia (triglycerides \> 500 mg/dl, total cholesterol \> 350 mg/dl) or taking lipid-lowering agents at the recruitment or 6 weeks before
• serious chronic disease requiring active treatment (example with glucocorticoids, antineoplastic agents, psychoactive agents, bronchodilators on a regular basis, insulin or oral hypoglycemic drugs)

Sponsors & Collaborators

• Poznan University of Medical Sciences: lead

Study Sites (1)

BBraun Avitum Dialysis Center

Nowy Tomyśl, Wielkopolska, 64-300, Poland

Location

Related Publications (5)

• Watanabe T, Sato K, Itoh F, Iso Y, Nagashima M, Hirano T, Shichiri M. The roles of salusins in atherosclerosis and related cardiovascular diseases. J Am Soc Hypertens. 2011 Sep-Oct;5(5):359-65. doi: 10.1016/j.jash.2011.06.003.

  PMID: 21925457 BACKGROUND

• Ti Y, Wang F, Wang ZH, Wang XL, Zhang W, Zhang Y, Bu PL. Associations of serum salusin-alpha levels with atherosclerosis and left ventricular diastolic dysfunction in essential hypertension. J Hum Hypertens. 2012 Oct;26(10):603-9. doi: 10.1038/jhh.2011.71. Epub 2011 Aug 11.

  PMID: 21833023 BACKGROUND

• Suzuki N, Shichiri M, Tateno T, Sato K, Hirata Y. Distinct systemic distribution of salusin-alpha and salusin-beta in the rat. Peptides. 2011 Apr;32(4):805-10. doi: 10.1016/j.peptides.2010.12.012. Epub 2010 Dec 28.

  PMID: 21193001 BACKGROUND

• Ozgen M, Koca SS, Dagli N, Balin M, Ustundag B, Isik A. Serum salusin-alpha level in rheumatoid arthritis. Regul Pept. 2011 Feb 25;167(1):125-8. doi: 10.1016/j.regpep.2010.12.003. Epub 2010 Dec 24.

  PMID: 21185876 BACKGROUND

• Nagashima M, Watanabe T, Shiraishi Y, Morita R, Terasaki M, Arita S, Hongo S, Sato K, Shichiri M, Miyazaki A, Hirano T. Chronic infusion of salusin-alpha and -beta exerts opposite effects on atherosclerotic lesion development in apolipoprotein E-deficient mice. Atherosclerosis. 2010 Sep;212(1):70-7. doi: 10.1016/j.atherosclerosis.2010.04.027. Epub 2010 May 4.

  PMID: 20684826 BACKGROUND

MeSH Terms

Conditions

Metabolic Syndrome; Diabetes Mellitus, Type 2; Hyperlipidemias

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Dyslipidemias; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Alicja E. Grzegorzewska, MD, PhD

  Chair and Department of Nephrology, Transplantology and Internal Diseases

  STUDY CHAIR

• Leszek Niepolski, MD, PhD

  BBraun Avitum Dialysis Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: October 5, 2011
• First Posted: October 7, 2011
• Study Start: October 1, 2011
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: October 7, 2014

Record last verified: 2014-10

Locations

PL (1)