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Phophate Lowering Trial

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ClinicalTrials.gov Identifier: NCT02209636
Recruitment Status : Active, not recruiting
First Posted : August 6, 2014
Last Update Posted : December 5, 2019
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:
The proposed research is a randomized-controlled trial to determine the effectiveness of reducing serum phosphorus using a phosphate binder, lanthanum carbonate, for improving the function of arteries in adults with moderate to severe chronic kidney disease (CKD). [COMIRB 13-0328] Additionally, it will determine phosphorus balance among adults with CKD and whether there is a difference in phosphorus balance after three months of treatment with lanthanum carbonate. [COMIRB 15-0384]

Condition or disease Intervention/treatment Phase
Chronic Kidney Disease Cardiovascular Disease Drug: Lanthanum carbonate Drug: placebo Drug: Ascorbic Acid Drug: Nitroglycerin Procedure: Flow-mediated dilation measurement Procedure: Aortic pulse-wave velocity Procedure: Endothelial cell collection Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phosphate Lowering to Treat Vascular Dysfunction in Chronic Kidney Disease
Actual Study Start Date : September 15, 2014
Actual Primary Completion Date : June 28, 2019
Estimated Study Completion Date : June 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arm Intervention/treatment
Experimental: Lanthanum carbonate
Eligible subjects who are randomly assigned to the experimental arm will receive lanthanum carbonate (1500-4500 mg/day in divided doses) titrated to serum phosphorus levels.
Drug: Lanthanum carbonate
Non-calcium containing phosphorus binder
Other Name: Fosrenol

Drug: Ascorbic Acid
Intravenous administration during measurement of flow mediated dilation.
Other Name: Vitamin C

Drug: Nitroglycerin
Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.

Procedure: Flow-mediated dilation measurement
Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.

Procedure: Aortic pulse-wave velocity
Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.

Procedure: Endothelial cell collection
Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.

Placebo Comparator: placebo
Eligible subjects who are randomly assigned to the placebo arm will receive placebo tablets (identical to the active lanthanum carbonate tablets) to be taken 3 times daily and titrated to serum phosphorus levels.
Drug: placebo
Table identical to lanthanum carbonate but with no active ingredient

Drug: Ascorbic Acid
Intravenous administration during measurement of flow mediated dilation.
Other Name: Vitamin C

Drug: Nitroglycerin
Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.

Procedure: Flow-mediated dilation measurement
Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.

Procedure: Aortic pulse-wave velocity
Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.

Procedure: Endothelial cell collection
Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.




Primary Outcome Measures :
  1. Brachial Artery Flow-mediated Dilation [ Time Frame: 12 weeks ]
    Measurement of how well the brachial artery dilates in response to shear stress. It is a measure of endothelial function.

  2. Aortic Pulse-wave Velocity [ Time Frame: 12 weeks ]
    The speed that blood travels from the carotid artery to the femoral artery. It is a measure of arterial stiffness.

  3. Phosphorus Balance (COMIRB 15-0384) [ Time Frame: 9 days ]
    Balance is defined as oral intake minus urine output minus stool output.


Secondary Outcome Measures :
  1. Oxidative stress-associated suppression of EDD and large elastic artery stiffness [ Time Frame: 12 weeks ]
    The influence of oxidative stress on FMD and aPWV will be determined by infusing a supraphysiologic dose of ascorbic acid or isovolemic saline. The difference in FMD and aPWV during ascorbic acid vs. saline infusion will be taken as a measure of the modulation of EDD/stiffness by oxidative stress.

  2. Vascular Endothelial Cell Protein Expression [ Time Frame: 12 weeks ]
    Measures of different protein markers on endothelial cells. Will help understand the underlying pathophysiology of vascular dysfunction in chronic kidney disease.

  3. Interleukin-6 and C-reactive protein to measure systemic inflammation [ Time Frame: 12 weeks ]
    This is a blood test.

  4. Oxidized low-density lipoprotein to measure systemic oxidized stress [ Time Frame: 12 weeks ]
    This is a blood test.



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 40-79, women must be post-menopausal
  • CKD stage IIIb or IV (estimated glomerular filtration rate by MDRD 15-45 mL/min/1.73m2), stable for 3 months
  • Serum phosphorus 2.8-5.5 mg/dL, stable for 3 months
  • Not using phosphate binders
  • Albumin > 3.0 g/dL
  • Free from alcohol dependence or abuse
  • Ability to provide informed consent
  • BMI < 40 kg/m2
  • Not taking medications that interact with agents administered during experimental sessions (e.g., sildenafil interacts with nitroglycerin)
  • For COMIRB 15-0384, completion of the prospective, randomized, placebo-controlled double-blind trial, Phosphorus Lowering to Treat Vascular Dysfunction in Chronic Kidney Disease (COMIRB 13-0328) or completion of 12-week run-in phase

Exclusion Criteria:

  • Life expectancy <1 year
  • Uncontrolled hypertension
  • History of severe liver disease
  • History of congestive heart failure (EF < 35%)
  • History of hospitalizations within the last 3 months
  • History of ileus or bowel obstruction
  • Active infection or antibiotic therapy
  • Expected kidney transplant in the next 6 months
  • Active vitamin D analogue use (i.e. calcitriol, paricalcitol, doxercalciferol)
  • Vasculitis requiring immunosuppressive therapy within the last year
  • Current tobacco abuse

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): NCT02209636


Locations
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United States, Colorado
Rocky Mountain Regional VA Medical Center, Aurora, CO
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
VA Office of Research and Development
Investigators
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Principal Investigator: Anna J Jovanovich, MD Rocky Mountain Regional VA Medical Center, Aurora, CO
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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT02209636    
Other Study ID Numbers: CLNB-006-13F
CX001030 ( Other Grant/Funding Number: VA )
First Posted: August 6, 2014    Key Record Dates
Last Update Posted: December 5, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by VA Office of Research and Development:
hyperphosphatemia
vascular dysfunction
chronic kidney disease
cardiovascular disease
endothelial dysfunction
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Cardiovascular Diseases
Urologic Diseases
Renal Insufficiency
Ascorbic Acid
Nitroglycerin
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Vasodilator Agents