NCT02523001

Brief Summary

The purpose of this study is to test the hypothesis that the function and/or regulation of urinary aquaporin 2 in hypercholesterolemic humans is affected by standard statin therapy, as compared with diet alone

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
37

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Oct 2013

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2013

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2014

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2015

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

August 10, 2015

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 14, 2015

Completed
Last Updated

August 14, 2015

Status Verified

August 1, 2015

Enrollment Period

7 months

First QC Date

August 10, 2015

Last Update Submit

August 11, 2015

Conditions

HypercholesterolemiaDiabetes Insipidus

Outcome Measures

Primary Outcomes (1)

  • uAQP2

    Urinary AQP2 excretion during therapy (statin or diet)

    0, 1, 4, 12 weeks

Secondary Outcomes (1)

  • Cholesterolemia

    0, 1, 4, 12 weeks

Study Arms (4)

NaĂ¯ve-S

Patients with hypercholesterolemia starting statin treatment for primary or secondary prevention of cardiovascular diseases.

ONC-S

Patients with hypercholesterolemia who had been treated with statin for at least one year and continued their previous therapy during the study period

NaĂ¯ve-MC

Patients with mild hypercholesterolemia either refusing initial statin treatment or intolerant to standard statin treatment and starting with monacolin K

NaĂ¯ve-Diet

Patients refusing an initial pharmacologic treatments and choosing the hypolipidic diet

Eligibility Criteria

Age40 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

Behavioral: diet Drug: statins, as required according to the ACC/AHA guidelines Diagnostic: anthropometric data, abdominal and carotid ultrasonography, serum (lipids, renal function) and urinary (AQP2, osmolality) dosages at enrollment and during a 3-months follow up (week 0, 1, 4, 12)

You may qualify if:

  • patients on primary prevention requiring moderate reduction of LDL-cholesterol according to the ACC/AHA Guidelines
  • age 40 to 75 years
  • estimated 10-year ASCVD risk ≥7.5%

You may not qualify if:

  • concomitant type 1 or type 2 diabetes
  • blood hypertension
  • concomitant use of diuretics or other drugs interfering with simvastatin

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Biomedical Sciences Human Oncology - Clinica Medica "A. Murri"

Bari, 70124, Italy

Location

Related Publications (19)

  • Greenwood J, Steinman L, Zamvil SS. Statin therapy and autoimmune disease: from protein prenylation to immunomodulation. Nat Rev Immunol. 2006 May;6(5):358-70. doi: 10.1038/nri1839.

    PMID: 16639429BACKGROUND

  • Pisitkun T, Shen RF, Knepper MA. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13368-73. doi: 10.1073/pnas.0403453101. Epub 2004 Aug 23.

    PMID: 15326289BACKGROUND

  • Valenti G, Laera A, Pace G, Aceto G, Lospalluti ML, Penza R, Selvaggi FP, Chiozza ML, Svelto M. Urinary aquaporin 2 and calciuria correlate with the severity of enuresis in children. J Am Soc Nephrol. 2000 Oct;11(10):1873-1881. doi: 10.1681/ASN.V11101873.

    PMID: 11004218BACKGROUND

  • Kanno K, Sasaki S, Hirata Y, Ishikawa S, Fushimi K, Nakanishi S, Bichet DG, Marumo F. Urinary excretion of aquaporin-2 in patients with diabetes insipidus. N Engl J Med. 1995 Jun 8;332(23):1540-5. doi: 10.1056/NEJM199506083322303.

    PMID: 7537863BACKGROUND

  • Valenti G, Laera A, Gouraud S, Pace G, Aceto G, Penza R, Selvaggi FP, Svelto M. Low-calcium diet in hypercalciuric enuretic children restores AQP2 excretion and improves clinical symptoms. Am J Physiol Renal Physiol. 2002 Nov;283(5):F895-903. doi: 10.1152/ajprenal.00354.2001.

    PMID: 12372764BACKGROUND

  • Wade JB. Statins affect AQP2 traffic. Am J Physiol Renal Physiol. 2011 Aug;301(2):F308. doi: 10.1152/ajprenal.00248.2011. Epub 2011 May 11. No abstract available.

    PMID: 21561996BACKGROUND

  • Li W, Zhang Y, Bouley R, Chen Y, Matsuzaki T, Nunes P, Hasler U, Brown D, Lu HA. Simvastatin enhances aquaporin-2 surface expression and urinary concentration in vasopressin-deficient Brattleboro rats through modulation of Rho GTPase. Am J Physiol Renal Physiol. 2011 Aug;301(2):F309-18. doi: 10.1152/ajprenal.00001.2011. Epub 2011 Apr 20.

    PMID: 21511701BACKGROUND

  • Grunfeld JP, Rossier BC. Lithium nephrotoxicity revisited. Nat Rev Nephrol. 2009 May;5(5):270-6. doi: 10.1038/nrneph.2009.43.

    PMID: 19384328BACKGROUND

  • Frokiaer J, Marples D, Knepper MA, Nielsen S. Bilateral ureteral obstruction downregulates expression of vasopressin-sensitive AQP-2 water channel in rat kidney. Am J Physiol. 1996 Apr;270(4 Pt 2):F657-68. doi: 10.1152/ajprenal.1996.270.4.F657.

    PMID: 8967344BACKGROUND

  • Marples D, Frokiaer J, Dorup J, Knepper MA, Nielsen S. Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex. J Clin Invest. 1996 Apr 15;97(8):1960-8. doi: 10.1172/JCI118628.

    PMID: 8621781BACKGROUND

  • Bustamante M, Hasler U, Leroy V, de Seigneux S, Dimitrov M, Mordasini D, Rousselot M, Martin PY, Feraille E. Calcium-sensing receptor attenuates AVP-induced aquaporin-2 expression via a calmodulin-dependent mechanism. J Am Soc Nephrol. 2008 Jan;19(1):109-16. doi: 10.1681/ASN.2007010092. Epub 2007 Nov 21.

    PMID: 18032798BACKGROUND

  • Procino G, Carmosino M, Tamma G, Gouraud S, Laera A, Riccardi D, Svelto M, Valenti G. Extracellular calcium antagonizes forskolin-induced aquaporin 2 trafficking in collecting duct cells. Kidney Int. 2004 Dec;66(6):2245-55. doi: 10.1111/j.1523-1755.2004.66036.x.

    PMID: 15569313BACKGROUND

  • Moeller HB, Rittig S, Fenton RA. Nephrogenic diabetes insipidus: essential insights into the molecular background and potential therapies for treatment. Endocr Rev. 2013 Apr;34(2):278-301. doi: 10.1210/er.2012-1044. Epub 2013 Jan 29.

    PMID: 23360744BACKGROUND

  • Patrick L, Uzick M. Cardiovascular disease: C-reactive protein and the inflammatory disease paradigm: HMG-CoA reductase inhibitors, alpha-tocopherol, red yeast rice, and olive oil polyphenols. A review of the literature. Altern Med Rev. 2001 Jun;6(3):248-71.

    PMID: 11410071BACKGROUND

  • Bonfrate L, Procino G, Wang DQ, Svelto M, Portincasa P. A novel therapeutic effect of statins on nephrogenic diabetes insipidus. J Cell Mol Med. 2015 Feb;19(2):265-82. doi: 10.1111/jcmm.12422. Epub 2015 Jan 16.

    PMID: 25594563RESULT

  • Murer L, Addabbo F, Carmosino M, Procino G, Tamma G, Montini G, Rigamonti W, Zucchetta P, Della Vella M, Venturini A, Zacchello G, Svelto M, Valenti G. Selective decrease in urinary aquaporin 2 and increase in prostaglandin E2 excretion is associated with postobstructive polyuria in human congenital hydronephrosis. J Am Soc Nephrol. 2004 Oct;15(10):2705-12. doi: 10.1097/01.ASN.0000139689.94776.7A.

    PMID: 15466275RESULT

  • Procino G, Milano S, Carmosino M, Barbieri C, Nicoletti MC, Li JH, Wess J, Svelto M. Combination of secretin and fluvastatin ameliorates the polyuria associated with X-linked nephrogenic diabetes insipidus in mice. Kidney Int. 2014 Jul;86(1):127-38. doi: 10.1038/ki.2014.10. Epub 2014 Feb 12.

    PMID: 24522493RESULT

  • Procino G, Barbieri C, Carmosino M, Rizzo F, Valenti G, Svelto M. Lovastatin-induced cholesterol depletion affects both apical sorting and endocytosis of aquaporin-2 in renal cells. Am J Physiol Renal Physiol. 2010 Feb;298(2):F266-78. doi: 10.1152/ajprenal.00359.2009. Epub 2009 Nov 18.

    PMID: 19923410RESULT

  • Procino G. Fluvastatin Increases AQP2 Urine Excretion in a Dyslipidemic Patient with Nephrogenic Diabetes Insipidus: An In Vivo and In Vitro Study. Journal of Diabetes & Metabolism 2014; 5(7); 1000408

    RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood analyses (serum lipids, creatininemia, glucose, bilirubin) Urines (creatininuria, urinary AQP2)

MeSH Terms

Conditions

HypercholesterolemiaDiabetes Insipidus

Condition Hierarchy (Ancestors)

HyperlipidemiasDyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesPituitary DiseasesEndocrine System Diseases

Study Officials

  • Piero Portincasa

    University of Bari Medical School

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine, PhD

Study Record Dates

First Submitted

August 10, 2015

First Posted

August 14, 2015

Study Start

October 1, 2013

Primary Completion

May 1, 2014

Study Completion

July 1, 2015

Last Updated

August 14, 2015

Record last verified: 2015-08

Locations

IT(1)