Phosphate Lowering in CKD Trial

NCT02209636 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: CLNB-006-13FCX001030
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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. \[COMIRB 15-0384\]

Conditions

Chronic Kidney Disease; Cardiovascular Disease

Keywords

hyperphosphatemia; vascular dysfunction; chronic kidney disease; cardiovascular disease; endothelial dysfunction

Outcome Measures

Primary Outcomes (3)

• Brachial Artery Flow-mediated Dilation

  Measurement of how well the brachial artery dilates in response to shear stress. It is a measure of endothelial function. It is reported as "percent change", which represents the change in dilation of the artery before and after occlusion. Brachial artery flow-mediated dilation will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change brachial artery flow mediated dilation from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.

  baseline and 12 weeks

• Aortic Pulse-wave Velocity

  The speed that blood travels from the carotid artery to the femoral artery, expressed as cm/s (centimeters/second). It is a measure of arterial stiffness. Aortic pulse-wave velocity will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change aortic pulse wave velocity from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.

  baseline and 12 weeks

• Phosphorus Balance Sub-study (COMIRB 15-0384)

  Balance is defined as oral intake minus urine output minus stool output.

  9 days from the start of the sub-study, approximately 13 weeks and 2 days from the start of the Main/Parent Study

Secondary Outcomes (5)

• Oxidative Stress-associated Suppression of EDD

  baseline and 12 weeks

• Vascular Endothelial Cell Protein Expression

  baseline and 12 weeks

• Interleukin-6 to Measure Systemic Inflammation

  baseline and 12 weeks

• Oxidized Low-density Lipoprotein (Ox-LDL) to Measure Systemic Oxidized Stress

  baseline and 12 weeks

• C-reactive Protein to Measure Systemic Inflammation

  baseline and 12 weeks

Study Arms (2)

Lanthanum carbonate

EXPERIMENTAL

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; Drug: Ascorbic Acid; Drug: Nitroglycerin; Procedure: Flow-mediated dilation measurement; Procedure: Aortic pulse-wave velocity; Procedure: Endothelial cell collection

placebo

PLACEBO COMPARATOR

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; Drug: Ascorbic Acid; Drug: Nitroglycerin; Procedure: Flow-mediated dilation measurement; Procedure: Aortic pulse-wave velocity; Procedure: Endothelial cell collection

Interventions

Lanthanum carbonate DRUG

Non-calcium containing phosphorus binder

Also known as: Fosrenol

Lanthanum carbonate

placebo DRUG

Table identical to lanthanum carbonate but with no active ingredient

placebo

Ascorbic Acid DRUG

Intravenous administration during measurement of flow mediated dilation.

Also known as: Vitamin C

Lanthanum carbonate; placebo

Nitroglycerin DRUG

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

Lanthanum carbonate; placebo

Flow-mediated dilation measurement PROCEDURE

Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.

Lanthanum carbonate; placebo

Aortic pulse-wave velocity PROCEDURE

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.

Lanthanum carbonate; placebo

Endothelial cell collection PROCEDURE

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.

Lanthanum carbonate; placebo

Eligibility Criteria

• Age: 40 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• Jovanovich A, Struemph T, You Z, Wang W, Farmer-Bailey H, Bispham N, Levi M, Schwartz GG, Nowak KL, Chonchol M. Effect of Lanthanum Carbonate on Serum Phosphate, Oxidative Stress, and Vascular Dysfunction in CKD: A Mechanistic Randomized Controlled Trial. Kidney360. 2024 Jul 1;5(7):959-966. doi: 10.34067/KID.0000000000000465. Epub 2024 May 23.

  PMID: 38781013 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Cardiovascular Diseases; Hyperphosphatemia

Interventions

lanthanum carbonate; Ascorbic Acid; Nitroglycerin

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; Phosphorus Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Nitro Compounds

Results Point of Contact

• Title: Anna Jovanovich, MD
• Organization: Rocky Mountain VA Medical Center

anna.jovanovich@va.gov

303-724-8677

Study Officials

• Anna J Jovanovich, MD

  Rocky Mountain Regional VA Medical Center, Aurora, CO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2014
• First Posted: August 6, 2014
• Study Start: September 15, 2014
• Primary Completion: June 28, 2019
• Study Completion: December 20, 2019
• Last Updated: August 26, 2022
• Results First Posted: August 26, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)