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Diurnal Variation in Markers of Mineral and Bone Disease in Chronic Kidney Disease

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ClinicalTrials.gov Identifier: NCT03698422
Recruitment Status : Recruiting
First Posted : October 8, 2018
Last Update Posted : October 8, 2018
Sponsor:
Information provided by (Responsible Party):
Ditte Hansen, Herlev Hospital

Brief Summary:
The purpose of this study is to examine whether there are diurnal variations in magnesium and other markers related to mineral metabolism in blood from patients with chronic kidney disease (CKD) compared to healthy controls.

Condition or disease Intervention/treatment
Chronic Kidney Diseases Mineral Metabolism Disorder Diagnostic Test: Blood and urine samples

Detailed Description:

CKD is associated with a mortality rate 5-10 times higher than in the general population, which is driven by a high rate of cardiovascular disease. Several cohort studies have revealed an association between hypomagnesaemia and increased mortality in patients with CKD as well as faster progression of CKD. Additionally, studies in cultured vascular smooth muscle cells (VSMC) and in rodents with CKD have shown that Mg inhibits vascular calcification.

The exact mechanism behind the inhibitory effect of Mg on vascular calcification is incompletely understood, but seems to be related to an inhibitory effect on the formation and precipitation of hydroxyapatite and delayed formation of secondary calciprotein particles, both of which have been shown to induce calcification of VSMC in vitro. Mg blocks the calcium (Ca) influx across the cell membrane in the VSMC. Mg has some affinity for the Ca sensing receptor, which has been shown to be involved in the calcification of VSMC, and might thus inhibit vascular calcification in a manner similar to other calcimimetics.

Thus, increasing serum Mg has been proposed as a possible treatment to prevent vascular calcification in CKD. However, any diurnal variation in serum Mg and other markers of mineral metabolism related to vascular calcification in CKD have not previously been described. This is relevant as monitoring of treatment with Mg supplementation might potentially be dangerous, if there are significant diurnal changes in serum Mg. Therefore, we wish to conduct a prospective controlled clinical trial to investigate any diurnal changes in Mg other markers of mineral metabolism in healthy controls, patients with predialysis CKD and patients with end-stage kidney disease (ESKD).


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Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Diurnal Variation in Markers of Mineral and Bone Disease in Chronic Kidney Disease - An Observational Study
Actual Study Start Date : October 3, 2018
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : June 30, 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Healthy controls

Estimated glomerular filtration rate (eGFR) > 60 mL/min for > 3 months and no known current or chronic medical or surgical conditions.

Blood and urine samples are collected for every 3rd hour during 24 hours

Diagnostic Test: Blood and urine samples
Subjects will be admitted to the Department of Nephrology, Herlev and Gentofte Hospital, Herlev, Denmark, for 24-hour observation with measurements of serum and urine at three-hour intervals.

Predialysis CKD subjects

Estimated glomerular filtration rate (eGFR) between 30 and 15 mL/min for > 3 months (i.e. CKD stage 4).

Blood and urine samples are collected for every 3rd hour during 24 hours

Diagnostic Test: Blood and urine samples
Subjects will be admitted to the Department of Nephrology, Herlev and Gentofte Hospital, Herlev, Denmark, for 24-hour observation with measurements of serum and urine at three-hour intervals.

ESKD subjects

Maintenance haemodialysis treatment for > 3 months for ESKD and with anuria (urine excretion < 100 mL/day).

Blood and urine samples are collected for every 3rd hour during 24 hours

Diagnostic Test: Blood and urine samples
Subjects will be admitted to the Department of Nephrology, Herlev and Gentofte Hospital, Herlev, Denmark, for 24-hour observation with measurements of serum and urine at three-hour intervals.




Primary Outcome Measures :
  1. Diurnal change in serum magnesium within groups [ Time Frame: 24 hours ]
    change in serum magnesium (mmol/l) within Groups The changes within groups over several timepoints will be compared with linear mixed effect models


Secondary Outcome Measures :
  1. Change in serum magnesium between groups [ Time Frame: 24 hours ]
    Change in serum magnesium (mmol/l) between Groups The overall magnesium levels will be compared between groups by comparing the total mean of measurements for each group.

  2. Change in ionized calcium [ Time Frame: 24 hours ]
    Change in p-ionized calcium within and between groups

  3. Change in p-phosphate [ Time Frame: 24 hours ]
    Change in p-phosphate within and between groups

  4. Change in p-PTH [ Time Frame: 24 hours ]
    Change in p-PTH within and between groups

  5. Change in p-FGF23 [ Time Frame: 24 hours ]
    Change in p-FGF23 within and between groups

  6. Change in s-calcification propensity score [ Time Frame: 24 hours ]
    Change in s-calcification propensity score within and between groups

  7. Change in u-magnesium [ Time Frame: 24 hours ]
    Change in u-magnesium within and between groups


Biospecimen Retention:   Samples Without DNA
serum and plasma samples are collected


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

For healthy controls:

estimated glomerular filtration rate (eGFR) > 60 mL/min for > 3 months and no known current or chronic medical or surgical conditions.

For predialysis CKD subjects:

estimated glomerular filtration rate (eGFR) between 30 and 15 mL/min for > 3 months (i.e. CKD stage 4).

For ESKD subjects:

maintenance haemodialysis treatment for > 3 months for ESKD and with anuria (urine excretion < 100 mL/day).

Criteria

Inclusion Criteria:

  • Age ≥ 18 years.
  • Serum Mg between 0.7 and 1.1 mmol/L on average of previous measurements over the last 6 months.
  • Serum ionised Ca between 1.10 and 1.35 mmol/L on average of previous measurements over the last 6 months.
  • Serum phosphate (PO4) between 0.7 and 1.8 mmol/L on average of previous measurements over the last 6 months.
  • A negative pregnancy test for women of childbearing age.
  • Written informed consent.
  • For healthy controls - estimated glomerular filtration rate (eGFR) > 60 mL/min for > 3 months and no known current or chronic medical or surgical conditions.
  • For predialysis CKD subjects - estimated glomerular filtration rate (eGFR) between 30 and 15 mL/min for > 3 months (i.e. CKD stage 4).
  • For ESKD subjects - maintenance haemodialysis treatment for > 3 months for ESKD and with anuria (urine excretion < 100 mL/day).

Exclusion Criteria:

  • Diagnosis of diabetes mellitus.
  • Kidney transplant recipient.
  • Parathyroid hormone (PTH) > 66 ρmol/L during the previous 3 months.
  • Previous parathyroidectomy.
  • Current treatment with Mg containing medication or supplements.
  • Current treatment with calcimimetics.
  • Current treatment with immunosuppressive drugs.
  • Active malignant disease.
  • Blood haemoglobin < 6.0 mmol/L
  • Any condition impairing Mg absorption from the gastrointestinal tract (e.g. short bowel syndrome, chronic pancreatitis).
  • Other diseases or conditions, which, in the opinion of the site investigator, would prevent participation in or completion of trial.
  • Pregnancy or breastfeeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03698422


Contacts
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Contact: Astrid Steen S Møller 61313839 astrid.steen.sand.moeller.01@regionh.dka
Contact: Ditte Hansen, PhD 38682056 ditte.hansen.04@regionh.dk

Locations
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Denmark
Herlev Hospital Recruiting
Herlev, Denmark, 2730
Contact: Astrid SS Møller    38682056    astrid.steen.sand.moeller.01@regionh.dk   
Sponsors and Collaborators
Herlev Hospital
Investigators
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Principal Investigator: Ditte Hansen, PhD Herlev Hospital

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Responsible Party: Ditte Hansen, Associate professor, Herlev Hospital
ClinicalTrials.gov Identifier: NCT03698422     History of Changes
Other Study ID Numbers: H-18037663
First Posted: October 8, 2018    Key Record Dates
Last Update Posted: October 8, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Metabolic Diseases
Bone Diseases
Urologic Diseases
Renal Insufficiency
Musculoskeletal Diseases