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Renal Failure Chronic Requiring HemodialysisPhase 4NCT01448174

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

A Phase 4 study testing Atorvastatin in people with Renal Failure Chronic Requiring Hemodialysis and Metabolic Syndrome, run by Poznan University of Medical Sciences at 1 site in Poland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
What is being tested?
Atorvastatin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
310 participants
Where
1 sitePoland
Study dates
Oct 2011to Oct 2014
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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)
  • women of child-bearing potential using an effective form of hormonal birth control, pregnant or lactating women

Trial locations and contacts

1 site in 1 country.

Poland1 site
  • BBraun Avitum Dialysis Center

    Nowy Tomyśl, Wielkopolska, 64-300

Other trials in Poland

About this study

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.

Read the 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
  • Lipoprotein(a)
  • 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 correlations/associations 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.

Being tested
Atorvastatin
Keywords
salusin-alpha, atorvastatin, CD36, Hemodialysis
Medical subject headings
Metabolic Syndrome, Diabetes Mellitus, Type 2, Hyperlipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtorvastatinDrug

    Also called ATC: C 10 AA 05

    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.
Study groups in NCT01448174
Study groupRoleWhat they receive
atorvastatinActive comparatorThe 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
Receives: Drug: Atorvastatin
Lifestyle counselingNo interventionProtocol 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 interventionNot described

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. normalization of serum LDL cholesterol

    Measured: 30 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Oct 2011 (estimated)
  2. Study startOct 2011
  3. Primary completionOct 2014
  4. Study completionOct 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
310 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01448174
Sponsor's protocol ID
ALGN-001
Status last verified
Oct 2014
First submitted
5 Oct 2011
Last updated
7 Oct 2014
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 21925457
  • 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.

    PubMed 21833023
  • 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.

    PubMed 21193001
  • 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.

    PubMed 21185876
  • 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.

    PubMed 20684826

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Atorvastatin in people with Renal Failure Chronic Requiring Hemodialysis and Metabolic Syndrome, run by Poznan University of Medical Sciences at 1 site in Poland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

normalization of serum LDL cholesterol (time frame: 30 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01448174, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2014.

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