Effects of Vitamin D on Renal Blood Flow, Proteinuria and Inflammation in Patients With Chronic Kidney Disease

This study has been withdrawn prior to enrollment.
(Difficult to enroll eligible subjects.)
Sponsor:
Information provided by (Responsible Party):
Kambiz Kalantarinia, University of Virginia
ClinicalTrials.gov Identifier:
NCT01426724
First received: August 29, 2011
Last updated: December 17, 2013
Last verified: December 2013
  Purpose

Active forms of vitamin D and its analogs are used to treat elevated parathyroid hormone levels and bone disease in chronic kidney disease (CKD). More recent animal and human studies suggest that treatment with vitamin D may be associated with reduction of inflammation and urinary protein loss as well as reduction the activity of the renin angiotensin system (RAS) in addition to its effects on the bone metabolism. The investigators of this study have used the new technique of contrast enhanced ultrasound (CEU) to measure the flow of blood to the kidney in other human studies. In this study, the investigators will investigate if 3 month of treatment with an active form of vitamin D in individuals with kidney disease and high parathyroid hormone levels would reduce protein loss in the urine. The investigators will also look at the potential changes in blood flow to the kidney using CEU, kidney function (GFR), inflammation and activity of RAS in response to treatment with active form of vitamin D. Finally, they will examine the association between reduction of protein loss in the urine as shown in other studies with any of the other factors measured (e.g, change in blood flow or inflammation).


Condition Intervention
Chronic Kidney Disease
Secondary Hyperparathyroidism
Drug: Contrast Enhanced Ultrasonography

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Effects of Active Form of Vitamin D on Renal Blood Flow, Glomerular Filtration Rate, Proteinuria and Inflammation in Patients With Chronic Kidney Disease and Hyperparathyroidism

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Change in proteinuria compared to baseline as determined by spot urine protein to creatinine ratio (PCR) [ Time Frame: Subjects must be on Vitamin D for 90 days (plus or minus 10 days) ] [ Designated as safety issue: No ]
    The pre to post-intervention change in urinary protein to creatinine ratio (PCR) will be analyzed either by way of the common paired Students t-test or the by way of paired Wilcoxon test. The paired Student t-test will be utilized if the measurements of the pre to post-intervention change in PCR are normally distribution, otherwise the ranked based paired Wilcoxon test will be utilized.


Secondary Outcome Measures:
  • Change in renal blood flow compared to baseline as determined by contrast enhanced ultrasound. [ Time Frame: Subjects must be on Vitamin D for 90 days (plus or minus 10 days) ] [ Designated as safety issue: No ]
    Baseline RBF will be measured using contrast enhanced ultrasound. subjects will be treated with one of the active forms of vitamin D for 90 days. Measurement of RBF usinf CEU will be repeated. Same statisticak methods will be used for this outcome as the primary outcome of the study.

  • Association between changes from baseline in PCR and RBF [ Time Frame: Subjects must be on Vitamin D for 90 days (plus or minus 10 days) ] [ Designated as safety issue: No ]
    We will examine whether the pre-intervention to post-intervention changes in PCR were associated with changes in either renal blood flow. Spearman rank correlations and Spearman partial-rank correlations will be utilized to examine possible associations. With regard to hypothesis testing, the null hypothesis of no association will be rejected based on a p≤0.05 decision rule.

  • Association between changes from baseline in PCR and GFR [ Time Frame: Subjects must be on Vitamin D for 90 days (plus or minus 10 days) ] [ Designated as safety issue: No ]
    We will examine whether the pre-intervention to post-intervention changes in PCR were associated with changes in GFR. Spearman rank correlations and Spearman partial-rank correlations will be utilized to examine possible associations. With regard to hypothesis testing, the null hypothesis of no association will be rejected based on a p≤0.05 decision rule.

  • Association between changes from baseline in PCR and concentration of biomarkers of inflammation [ Time Frame: Subjects must be on Vitamin D for 90 days (plus or minus 10 days) ] [ Designated as safety issue: No ]
    We will examine whether the pre-intervention to post-intervention changes in PCR were associated with changes in CRP, IL-1, IL-6, or TNF-alpha. Spearman rank correlations and Spearman partial-rank correlations will be utilized to examine possible associations. With regard to hypothesis testing, the null hypothesis of no association will be rejected based on a p≤0.05 decision rule.

  • Association between changes from baseline in PCR and activity of the renin angiotensin system. [ Time Frame: Subjects must be on Vitamin D for 90 days (plus or minus 10 days) ] [ Designated as safety issue: No ]
    We will examine whether the pre-intervention to post-intervention changes in PCR were associated with changes in plasma renin-activity and plasma aldosterone concentration. Spearman rank correlations and Spearman partial-rank correlations will be utilized to examine possible associations. With regard to hypothesis testing, the null hypothesis of no association will be rejected based on a p≤0.05 decision rule.


Enrollment: 0
Study Start Date: September 2011
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Contrast Enhanced Ultrasonography
    Definity microbubbles will be infused intravenously at a rate of 2mL/min. contrast enhanced images of the kidneys will be obtained during the infusion and following the destruction of microbubbles within the kidney tissue with ultrasound to measure renal blood flow two times within a 90 day (plus or minus 10 day) window
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  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adults (ages 18 - 75 years)
  2. A diagnosis of chronic kidney disease (CKD) with a glomerular filtration rate (GFR) in the range of 20 - 60 ml/min/1.73 m2.
  3. Proteinuria confirmed at least twice by one of the following (at least one sample within the last 6 months),

    • 24-hour urine protein excretion of at least 150 mg/day OR
    • spot urine protein to creatinine ratio (PCR) of greater than 0.15 OR
    • spot urine albumin to creatinine ratio (ACR) greater than 100 mg/g
  4. A recent diagnosis of secondary hyperparathyroidism of renal origin by the patient's nephrologist scheduled for treatment with an active from of vitamin D.
  5. Available results for serum intact parathyroid hormone (iPTH), calcium and phosphorus within 6 months from the study enrollment date.
  6. Treatment with a stable dose of an angiotensin receptor blocker (ARB), angiotensin converting enzyme inhibitor (ACE-I) or rennin inhibitor within the last 2 months before enrollment in the study.

Exclusion Criteria:

  1. GFR less than 20 or greater than 60 ml/min/1.73 m2.
  2. Treatment with an active form of vitamin D, including Calcitriol (Rocaltrol), Paricalcitol (Zemplar) and Doxercalciferol (Hectorol) within the last 3 months.
  3. Need for renal replacement therapy within the next three months.
  4. History of any organ transplantation requiring immunosuppressive therapy.
  5. Chronic treatment with anti-inflammatory agents including NSAIDs, steroids or cytotoxic agents.
  6. Diagnoses of primary or tertiary hyperparathyroidism.
  7. Serum intact parathyroid hormone (PTH) concentration greater than 250 pg/mL.
  8. Serum calcium greater than 10.4 mg/dL.Serum phosphorous greater than 5 mg/dL.
  9. Active malignancy.
  10. History of systemic inflammatory diseases such as, systemic lupus, rheumatoid arthritis or vasculitis.
  11. History of pulmonary hypertension, intracardiac shunt or unstable cardiopulmonary disease.
  12. Women who are pregnant.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01426724

Locations
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
University of Virginia
  More Information

No publications provided

Responsible Party: Kambiz Kalantarinia, MD, Principal Investigator, University of Virginia
ClinicalTrials.gov Identifier: NCT01426724     History of Changes
Other Study ID Numbers: 15043
Study First Received: August 29, 2011
Last Updated: December 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Virginia:
Vitamin D
Chronic Kidney Disease
Hyperparathyroidism
Renal Blood Flow
Proteinuria
Inflammation
Renin Angiotensin System

Additional relevant MeSH terms:
Hyperparathyroidism
Hyperparathyroidism, Secondary
Inflammation
Kidney Diseases
Proteinuria
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Parathyroid Diseases
Endocrine System Diseases
Pathologic Processes
Urologic Diseases
Urination Disorders
Urological Manifestations
Signs and Symptoms
Renal Insufficiency
Vitamin D
Ergocalciferols
Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on April 23, 2014