Phosphate Microvascular Study

NCT03594539 | Unknown DMC

• 1 other identifier: VAH170095
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

Elevated phosphate concentrations in the blood have been associated with multiple negative health outcomes in patients with chronic kidney disease as well as in the general population. These negative outcomes include an increased risk of vascular complications like heart attack and stroke. While complications like heart attack and stroke reflect obstructive disease in large blood vessels, recent evidence suggests that elevated phosphate concentrations may first lead to disease in small blood vessels. This single site clinical trial will randomize 20 veterans with end stage renal disease on hemodialysis to either a phosphate binder or placebo and evaluated for changes in their microvascular function using laser-Doppler flowmtery and nail-fold capillaroscopy.

Conditions

End Stage Renal Disease; Hyperphosphatemia

Keywords

ESRD; Microvascular; Hyperphosphatemia; LDF

Outcome Measures

Primary Outcomes (1)

• % Change in flux of blood after skin heating to 44 C as measured using laser-Doppler flowmtery.

  Flux of blood through skin will be measured using a Perimed PF5000. This will be performed at baseline in a temperature controlled room. Baseline skin measurements will be made at 31C. Skin will then be heated to 44 C. The percent change will be the outcome. This outcome will be compared within each person at the conclusion of each arm. Measurements will all be made on the Monday or Tuesday, the day of the participant's first dialysis treatment of the week. Measurements will be made prior to dialysis.

  Performed at initial study visit, at the end of the first arm of the study (Day 14) and again at the end of the second arm of the study (Day 28)

Secondary Outcomes (1)

• Change in capillary count seen post occlusion from pre occlusion, as determined by nail-fold capillaroscopy.

  Performed at initial study visit, at the end of the first arm of the study (Day 14) and again at the end of the second arm of the study (Day 28)

Study Arms (2)

Standard

NO INTERVENTION

Participants will have their hyperphosphatemia managed with lanthanum carbonate 1 g with meals and 500 mg with snacks as per typical care, for 2 weeks.

Intervention

PLACEBO COMPARATOR

Participants will take a placebo instead of standard care with a phosphate binder, for 2 weeks.

Other: Withholding standard phosphate binder

Interventions

Withholding standard phosphate binder OTHER

In this trial, placebo represents the intervention and not the control. Standard therapy for hyperphosphatemia in end-stage renal disease includes treatment with a phosphate binder. In this trial the intervention will be to withhold the phosphate binder and use placebo instead. In this way the effect of a higher serum phosphate can be evaluated.

Intervention

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of ESRD on hemodialysis (HD) for \>90 days.
• Age \>21.
• Capacity to understand and sign informed consent as assess by principal investigator.
• On a phosphate binder with stable dose for \>2 weeks.
• Serum phosphate at screening visit of \<7.0.

You may not qualify if:

• Pregnancy.
• Actively breastfeeding.
• Use of oral contraceptives.
• Inability to take oral medications.
• History of medication non-compliance as assessed by the treating physician.
• Patients currently enrolled in another trial.
• Planned or expected surgical procedure during study period.
• Planned or expected hospitalization during study period.
• Corrected serum calcium greater than 10.2 mg/dl.
• Serum intact PTH \>1000 pg/ml
• Albumin \< 3 g/dl.
• Allergy or intolerance to lanthanum carbonate.
• Principal investigator deems patient to be unsuitable.
• Non-English speaking persons. (Study performed at VA, therefore do not anticipate this represents a significant portion of the population).

Sponsors & Collaborators

• Veterans Medical Research Foundation: lead
• San Diego Veterans Healthcare System: collaborator

Related Publications (3)

• O'Seaghdha CM, Hwang SJ, Muntner P, Melamed ML, Fox CS. Serum phosphorus predicts incident chronic kidney disease and end-stage renal disease. Nephrol Dial Transplant. 2011 Sep;26(9):2885-90. doi: 10.1093/ndt/gfq808. Epub 2011 Feb 3.

  PMID: 21292817 BACKGROUND

• Thambyrajah J, Landray MJ, McGlynn FJ, Jones HJ, Wheeler DC, Townend JN. Abnormalities of endothelial function in patients with predialysis renal failure. Heart. 2000 Feb;83(2):205-9. doi: 10.1136/heart.83.2.205.

  PMID: 10648498 BACKGROUND

• Stevens KK, Denby L, Patel RK, Mark PB, Kettlewell S, Smith GL, Clancy MJ, Delles C, Jardine AG. Deleterious effects of phosphate on vascular and endothelial function via disruption to the nitric oxide pathway. Nephrol Dial Transplant. 2017 Oct 1;32(10):1617-1627. doi: 10.1093/ndt/gfw252.

  PMID: 27448672 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic; Hyperphosphatemia

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; 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

Central Study Contacts

Charles Ginsberg, MD

CONTACT

8585528585; cginsberg@ucsd.edu

Joachim Ix, MD

CONTACT

8585528585; joeix@ucsd.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The pharmacy dispensing the drug will be responsible for generating placebo and distributing drug. The investigators, care providers and patient will not have access to this data. Study outcomes will be comparing arms but not with knowledge of which arm occurred when.
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to either lanthanum carbonate or placebo for 2 weeks. They will then be assigned to the other arm of the study. They will be in the alternate arm for 2 weeks and then complete the study,

Study Record Dates

• First Submitted: July 9, 2018
• First Posted: July 20, 2018
• Study Start: January 1, 2019
• Primary Completion: January 1, 2021
• Study Completion: July 17, 2021
• Last Updated: August 24, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF