Vascular CalcificationNCT03858413
a-Klotho in Relation to Calcification in the Coronary Arteries and Aortic Valve in Patients With Chronic Kidney Disease
An observational study of Vascular Calcification and Chronic Kidney Diseases, run by Royal Brompton & Harefield NHS Foundation Trust.
Trial summary
To define the correlation of the levels of a-Klotho with the severity of vascular calcification in the coronary arteries and aortic valve. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Vascular Calcification, Chronic Kidney Diseases
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 15 Jan 2016to 31 Dec 2018
- Phase
- Observational
- 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
- No healthy volunteers
- Adult, Older adult
Study population: Two different populations have been selected. First group with patients with chronic kidney disease under hemodialysis. Second group with patients with chronic kidney disease stage III stable for the last at least 3 months
Who may be able to join
- Patients with stable chronic kidney disease stage V under intermittent hemodialysis and, patients with stable chronic kidney disease stage III
Who cannot join
- Active cancer
- Inflammatory or granulomatous disease
- Primary hyperparathyroidism
- Patients unable to provide informed consent
About this study
Official title: Correlation of a-Klotho Levels With the Severity of Calcification in the Coronary Arteries and Aortic Valve in Patients With Chronic Kidney Disease
To define the correlation of the levels of a-Klotho with the severity of vascular calcification in the coronary arteries and aortic valve.
Read the detailed description
Vascular calcification is a well-defined risk factor for cardiovascular disease and a-Klotho has been suggested to be an implicating factor in the process of vascular calcification, particularly in patients with chronic kidney disease (CKD).
With this study the investigators will examine the possible correlation of the levels of secreted a-Klotho with the severity of vascular calcification in the coronary arteries and aortic valve in patients with CKD at different stages of CKD. More precisely, a-Klotho was measured in 30 patients with end-stage renal disease under intermittent regular hemodialysis and 30 outpatients with stable CKD stage III (estimated glomerular filtration rate between 30 and 59 mL/min/1.73^2).
Participants in both groups were eligible only if stable for at least the last 3 months pre-enrollment. Calcification will be calculated using the well-established Agatston score after submitting all patients to multi-slice computed tomography.
Continuous variables will be described as median (25th-75th percentile) and categorical variables as N (%). Variables will be compared between groups using the non-parametric Mann-Whitney U test for continuous and Fisher's exact test for categorical variables. Bivariate correlations of a-Klotho levels with clinical variables and calcification scores using the Spearman correlation coefficient will be examined. Identification of a-Klotho determinants, log-transformation of a-Klotho levels was done because of log-normal distribution and stepwise linear regression was used, with probability to remove the variable>0.1. Identification of determinants of coronary and aortic calcification was done via log-transformation of the corresponding calcium scores, (a value of 0 was assumed; log-transformed-1 for absent calcium) and, stepwise linear regression was used as above. Because of the small sample size, all regression estimates, and confidence intervals were calculated with re-sampling so that robust variable selection and stable estimates can be ensured.
- Conditions
- Vascular Calcification, Chronic Kidney Diseases
- Being tested
- No intervention
- Medical subject headings
- Vascular Calcification, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionDiagnostic test
No intervention
| Study group | Role | What they receive |
|---|---|---|
| Chronic kidney disease stage V | No intervention Receives: Diagnostic Test: No intervention | |
| Chronic kidney disease stage III | No intervention Receives: Diagnostic Test: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Agatston score in coronary arteries.
Calcification of coronary arteries will be measured with multi-slice CT and dedicated software to calculate Agatston score.
Initially, Hounsfield units will be measured and transformed into Agatston score net numbers.
A brief description of the method is provided below:
Method of calculation:
The calculation is based on the weighted density score given to the highest attenuation value (HU) multiplied by the area of the calcification speck.
Density factor: 130-199 HU: 1; 200-299 HU: 2; 300-399 HU: 3; 400+ HU: 4. The score of every calcified speck is summed up to give the total calcium score.
Measured: During enrollment.
Agatston score in aortic valve.
Calcification aortic valve will be measured with multi-slice CT and dedicated software to calculate Agatston score.
Initially, Hounsfield units will be measured and transformed into Agatston score net numbers.
A brief description of the method is provided below:
Method of calculation:
The calculation is based on the weighted density score given to the highest attenuation value (HU) multiplied by the area of the calcification speck.
Density factor: 130-199 HU: 1; 200-299 HU: 2; 300-399 HU: 3; 400+ HU: 4. The score of every calcified speck is summed up to give the total calcium score.
Measured: During enrollment.
Circulating a-Klotho.
Circulating a-Klotho levels will be measured in serum with the use of a commercially available ELISA kit. Concentration will be expressed in pg/mL.
Measured: During enrollment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2019
- Study start15 Jan 2016
- Primary completion31 Dec 2018
- Study completion31 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Vascular CalcificationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- AHEPA University Hospital
- Responsible party
- Principal investigator, Panagiotis Savvoulidis, Royal Brompton & Harefield NHS Foundation Trust
- Investigators
- Stavros Hadjimiltiades, Professor, Study director, Head of Interventional Cardiology Department
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03858413
- Sponsor's protocol ID
- 16/23-6-2016
- Status last verified
- Feb 2019
- First submitted
- 22 Feb 2019
- Last updated
- 28 Feb 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plans made to make IPD available to other researchers
Publications
Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997 Nov 6;390(6655):45-51. doi: 10.1038/36285.
PubMed 9363890Shiraki-Iida T, Aizawa H, Matsumura Y, Sekine S, Iida A, Anazawa H, Nagai R, Kuro-o M, Nabeshima Y. Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein. FEBS Lett. 1998 Mar 6;424(1-2):6-10. doi: 10.1016/s0014-5793(98)00127-6.
PubMed 9537505Olejnik A, Franczak A, Krzywonos-Zawadzka A, Kaluzna-Oleksy M, Bil-Lula I. The Biological Role of Klotho Protein in the Development of Cardiovascular Diseases. Biomed Res Int. 2018 Dec 24;2018:5171945. doi: 10.1155/2018/5171945. eCollection 2018.
PubMed 30671457Henaut L, Chillon JM, Kamel S, Massy ZA. Updates on the Mechanisms and the Care of Cardiovascular Calcification in Chronic Kidney Disease. Semin Nephrol. 2018 May;38(3):233-250. doi: 10.1016/j.semnephrol.2018.02.004.
PubMed 29753400Mencke R, Hillebrands JL; NIGRAM consortium. The role of the anti-ageing protein Klotho in vascular physiology and pathophysiology. Ageing Res Rev. 2017 May;35:124-146. doi: 10.1016/j.arr.2016.09.001. Epub 2016 Sep 28.
PubMed 27693241Navarro-Garcia JA, Fernandez-Velasco M, Delgado C, Delgado JF, Kuro-O M, Ruilope LM, Ruiz-Hurtado G. PTH, vitamin D, and the FGF-23-klotho axis and heart: Going beyond the confines of nephrology. Eur J Clin Invest. 2018 Apr;48(4). doi: 10.1111/eci.12902. Epub 2018 Feb 21.
PubMed 29394451Kuro-O M. The FGF23 and Klotho system beyond mineral metabolism. Clin Exp Nephrol. 2017 Mar;21(Suppl 1):64-69. doi: 10.1007/s10157-016-1357-6. Epub 2016 Nov 12.
PubMed 27838783Back M, Aranyi T, Cancela ML, Carracedo M, Conceicao N, Leftheriotis G, Macrae V, Martin L, Nitschke Y, Pasch A, Quaglino D, Rutsch F, Shanahan C, Sorribas V, Szeri F, Valdivielso P, Vanakker O, Kempf H. Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet. Front Cardiovasc Med. 2019 Jan 18;5:196. doi: 10.3389/fcvm.2018.00196. eCollection 2018.
PubMed 30713844Olauson H, Mencke R, Hillebrands JL, Larsson TE. Tissue expression and source of circulating alphaKlotho. Bone. 2017 Jul;100:19-35. doi: 10.1016/j.bone.2017.03.043. Epub 2017 Mar 18.
PubMed 28323144
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Correlation of a-Klotho Levels With the Severity of Calcification in the Coronary Arteries and Aortic Valve in Patients With Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT03858413
- Acronym / sponsor ID
- 16/23-6-2016
- Conditions
- Vascular Calcification, Chronic Kidney Diseases
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation TrustUniversity, hospital or other
- Collaborators
- AHEPA University Hospital
- Study start
- 15 Jan 2016 (actual)
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 28 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To define the correlation of the levels of a-Klotho with the severity of vascular calcification in the coronary arteries and aortic valve.
Detailed description
Vascular calcification is a well-defined risk factor for cardiovascular disease and a-Klotho has been suggested to be an implicating factor in the process of vascular calcification, particularly in patients with chronic kidney disease (CKD).
With this study the investigators will examine the possible correlation of the levels of secreted a-Klotho with the severity of vascular calcification in the coronary arteries and aortic valve in patients with CKD at different stages of CKD. More precisely, a-Klotho was measured in 30 patients with end-stage renal disease under intermittent regular hemodialysis and 30 outpatients with stable CKD stage III (estimated glomerular filtration rate between 30 and 59 mL/min/1.73^2).
Participants in both groups were eligible only if stable for at least the last 3 months pre-enrollment. Calcification will be calculated using the well-established Agatston score after submitting all patients to multi-slice computed tomography.
Continuous variables will be described as median (25th-75th percentile) and categorical variables as N (%). Variables will be compared between groups using the non-parametric Mann-Whitney U test for continuous and Fisher's exact test for categorical variables. Bivariate correlations of a-Klotho levels with clinical variables and calcification scores using the Spearman correlation coefficient will be examined. Identification of a-Klotho determinants, log-transformation of a-Klotho levels was done because of log-normal distribution and stepwise linear regression was used, with probability to remove the variable>0.1. Identification of determinants of coronary and aortic calcification was done via log-transformation of the corresponding calcium scores, (a value of 0 was assumed; log-transformed-1 for absent calcium) and, stepwise linear regression was used as above. Because of the small sample size, all regression estimates, and confidence intervals were calculated with re-sampling so that robust variable selection and stable estimates can be ensured.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chronic kidney disease stage V | – | Diagnostic Test: No interventionNo intervention |
| Chronic kidney disease stage III | – | Diagnostic Test: No interventionNo intervention |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Two different populations have been selected. First group with patients with chronic kidney disease under hemodialysis. Second group with patients with chronic kidney disease stage III stable for the last at least 3 months
Key inclusion criteria (1 listed)
- Patients with stable chronic kidney disease stage V under intermittent hemodialysis and, patients with stable chronic kidney disease stage III
Key exclusion criteria (4 listed)
- Active cancer
- Inflammatory or granulomatous disease
- Primary hyperparathyroidism
- Patients unable to provide informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No interventionNo intervention | Diagnostic test | Chronic kidney disease stage III, Chronic kidney disease stage V |
Primary outcome
Agatston score in coronary arteries.
Time frame: During enrollment.
Calcification of coronary arteries will be measured with multi-slice CT and dedicated software to calculate Agatston score. Initially, Hounsfield units will be measured and transformed into Agatston score net numbers. A brief description of the method is provided below: Method of calculation: The calculation is based on the weighted density score given to the highest attenuation value (HU) multiplied by the area of the calcification speck. Density factor: 130-199 HU: 1; 200-299 HU: 2; 300-399 HU: 3; 400+ HU: 4. The score of every calcified speck is summed up to give the total calcium score.
Agatston score in aortic valve.
Time frame: During enrollment.
Calcification aortic valve will be measured with multi-slice CT and dedicated software to calculate Agatston score. Initially, Hounsfield units will be measured and transformed into Agatston score net numbers. A brief description of the method is provided below: Method of calculation: The calculation is based on the weighted density score given to the highest attenuation value (HU) multiplied by the area of the calcification speck. Density factor: 130-199 HU: 1; 200-299 HU: 2; 300-399 HU: 3; 400+ HU: 4. The score of every calcified speck is summed up to give the total calcium score.
Circulating a-Klotho.
Time frame: During enrollment.
Circulating a-Klotho levels will be measured in serum with the use of a commercially available ELISA kit. Concentration will be expressed in pg/mL.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2019.
- Background: PubMed 9363890Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997 Nov 6;390(6655):45-51. doi: 10.1038/36285.
- Background: PubMed 9537505Shiraki-Iida T, Aizawa H, Matsumura Y, Sekine S, Iida A, Anazawa H, Nagai R, Kuro-o M, Nabeshima Y. Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein. FEBS Lett. 1998 Mar 6;424(1-2):6-10. doi: 10.1016/s0014-5793(98)00127-6.
- Background: PubMed 30671457Olejnik A, Franczak A, Krzywonos-Zawadzka A, Kaluzna-Oleksy M, Bil-Lula I. The Biological Role of Klotho Protein in the Development of Cardiovascular Diseases. Biomed Res Int. 2018 Dec 24;2018:5171945. doi: 10.1155/2018/5171945. eCollection 2018.
- Background: PubMed 29753400Henaut L, Chillon JM, Kamel S, Massy ZA. Updates on the Mechanisms and the Care of Cardiovascular Calcification in Chronic Kidney Disease. Semin Nephrol. 2018 May;38(3):233-250. doi: 10.1016/j.semnephrol.2018.02.004.
- Background: PubMed 27693241Mencke R, Hillebrands JL; NIGRAM consortium. The role of the anti-ageing protein Klotho in vascular physiology and pathophysiology. Ageing Res Rev. 2017 May;35:124-146. doi: 10.1016/j.arr.2016.09.001. Epub 2016 Sep 28.
- Background: PubMed 29394451Navarro-Garcia JA, Fernandez-Velasco M, Delgado C, Delgado JF, Kuro-O M, Ruilope LM, Ruiz-Hurtado G. PTH, vitamin D, and the FGF-23-klotho axis and heart: Going beyond the confines of nephrology. Eur J Clin Invest. 2018 Apr;48(4). doi: 10.1111/eci.12902. Epub 2018 Feb 21.
- Background: PubMed 27838783Kuro-O M. The FGF23 and Klotho system beyond mineral metabolism. Clin Exp Nephrol. 2017 Mar;21(Suppl 1):64-69. doi: 10.1007/s10157-016-1357-6. Epub 2016 Nov 12.
- Background: PubMed 30713844Back M, Aranyi T, Cancela ML, Carracedo M, Conceicao N, Leftheriotis G, Macrae V, Martin L, Nitschke Y, Pasch A, Quaglino D, Rutsch F, Shanahan C, Sorribas V, Szeri F, Valdivielso P, Vanakker O, Kempf H. Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet. Front Cardiovasc Med. 2019 Jan 18;5:196. doi: 10.3389/fcvm.2018.00196. eCollection 2018.
- Background: PubMed 28323144Olauson H, Mencke R, Hillebrands JL, Larsson TE. Tissue expression and source of circulating alphaKlotho. Bone. 2017 Jul;100:19-35. doi: 10.1016/j.bone.2017.03.043. Epub 2017 Mar 18.
- Individual participant dataSharing planned: No. No plans made to make IPD available to other researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stavros Hadjimiltiades, Professor study director
Head of Interventional Cardiology Department
Questions about this trial
What is this clinical trial studying?
An observational study of Vascular Calcification and Chronic Kidney Diseases, run by Royal Brompton & Harefield NHS Foundation Trust.
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 1 inclusion and 4 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 28 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
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.
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?
Agatston score in coronary arteries. (time frame: During enrollment.). The study lists 3 primary outcomes in all. 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 NCT03858413, which also lists 9 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 28 Feb 2019.