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

NCT01426724 | Withdrawn

• 1 other identifier: 15043
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Chronic Kidney Disease; Secondary Hyperparathyroidism

Keywords

Vitamin D; Chronic Kidney Disease; Hyperparathyroidism; Renal Blood Flow; Proteinuria; Inflammation; Renin Angiotensin System

Outcome Measures

Primary Outcomes (1)

• Change in proteinuria compared to baseline as determined by spot urine protein to creatinine ratio (PCR)

  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.

  Subjects must be on Vitamin D for 90 days (plus or minus 10 days)

Secondary Outcomes (5)

• Change in renal blood flow compared to baseline as determined by contrast enhanced ultrasound.

  Subjects must be on Vitamin D for 90 days (plus or minus 10 days)

• Association between changes from baseline in PCR and RBF

  Subjects must be on Vitamin D for 90 days (plus or minus 10 days)

• Association between changes from baseline in PCR and GFR

  Subjects must be on Vitamin D for 90 days (plus or minus 10 days)

• Association between changes from baseline in PCR and concentration of biomarkers of inflammation

  Subjects must be on Vitamin D for 90 days (plus or minus 10 days)

• Association between changes from baseline in PCR and activity of the renin angiotensin system.

  Subjects must be on Vitamin D for 90 days (plus or minus 10 days)

Interventions

Contrast Enhanced Ultrasonography DRUG

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (ages 18 - 75 years)
• A diagnosis of chronic kidney disease (CKD) with a glomerular filtration rate (GFR) in the range of 20 - 60 ml/min/1.73 m2.
• Proteinuria confirmed at least twice by one of the following (at least one sample within the last 6 months),
• 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
• A recent diagnosis of secondary hyperparathyroidism of renal origin by the patient's nephrologist scheduled for treatment with an active from of vitamin D.
• Available results for serum intact parathyroid hormone (iPTH), calcium and phosphorus within 6 months from the study enrollment date.
• 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.

You may not qualify if:

• GFR less than 20 or greater than 60 ml/min/1.73 m2.
• Treatment with an active form of vitamin D, including Calcitriol (Rocaltrol), Paricalcitol (Zemplar) and Doxercalciferol (Hectorol) within the last 3 months.
• Need for renal replacement therapy within the next three months.
• History of any organ transplantation requiring immunosuppressive therapy.
• Chronic treatment with anti-inflammatory agents including NSAIDs, steroids or cytotoxic agents.
• Diagnoses of primary or tertiary hyperparathyroidism.
• Serum intact parathyroid hormone (PTH) concentration greater than 250 pg/mL.
• Serum calcium greater than 10.4 mg/dL.Serum phosphorous greater than 5 mg/dL.
• Active malignancy.
• History of systemic inflammatory diseases such as, systemic lupus, rheumatoid arthritis or vasculitis.
• History of pulmonary hypertension, intracardiac shunt or unstable cardiopulmonary disease.
• Women who are pregnant.

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Hyperparathyroidism, Secondary; Hyperparathyroidism; Proteinuria; Inflammation

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Parathyroid Diseases; Endocrine System Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Principal Investigator

Study Record Dates

• First Submitted: August 29, 2011
• First Posted: August 31, 2011
• Study Start: September 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: May 21, 2014

Record last verified: 2014-05

Locations

US (1)