Clinical trial NCT03594539: Phosphate Microvascular Study
Official title: The Effects of Phosphate on Microvascular Function
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: End Stage Renal Disease
Hyperphosphatemia
Keywords: ESRD
Microvascular
Hyperphosphatemia
LDF
Lead sponsor: Veterans Medical Research Foundation
Sponsor class: OTHER
Collaborators: name: San Diego Veterans Healthcare System
First posted: 2018-07-20
Enrollment: 20
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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,
Primary purpose: DIAGNOSTIC

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.

Detailed description: Project Background: Recent studies have suggested that increased serum phosphate and phosphate intake may acute impair microvascular blood flow. However, this has never been directly tested using imaging techniques that directly measure microvascular flow. The end-stage renal disease population on hemodialysis at the VA San Diego is an ideal population to evaluate this effect.

Project Question: Does reduction of serum phosphate through the use of a phosphate binder (lanthanum carbonate) increase microvascular blood flow in persons with ESRD? Project Methods: The investigators propose a 4 week, randomized, double-blinded, placebo controlled, single-center, crossover trial. Participants will have their microvascular function assessed at the baseline of the study using laser-Doppler flowmetry and nail-fold capillaroscopy. They will then be randomized to either lanthanum carbonate or placebo for 2 weeks. Microvascular measurements will be repeated at the end of the 2 week period. Participants will then cross-over to the other study arm. After 2 weeks in the other study arm, they will have microvascular measurements repeated and the trial will then be complete. The primary outcome of the study will be the % change in skin blood flow after heating from 31 degrees Celsius to 44 degrees Celsius. This will be compared within each individual after they complete each arm of the study. Changes seen on nail-fold capillaroscopy, acceptability, safety, and adherence will be key secondary outcomes.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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).

Primary outcomes:
measure: % Change in flux of blood after skin heating to 44 C as measured using laser-Doppler flowmtery.
timeFrame: 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:
measure: Change in capillary count seen post occlusion from pre occlusion, as determined by nail-fold capillaroscopy.
timeFrame: 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)
Other outcomes:
Locations:
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.