Phosphate Microvascular Study

NCT ID: NCT03594539

Last Updated: 2018-08-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-01
• Study Completion Date: 2021-07-17

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.

Conditions

End Stage Renal Disease; Hyperphosphatemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: QUADRUPLE

Study Groups

Standard

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Intervention

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

Group Type: PLACEBO_COMPARATOR

Withholding standard phosphate binder

Intervention Type: 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.

Interventions

Withholding standard phosphate binder

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 Type: OTHER

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).

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

San Diego Veterans Healthcare System

FED

Sponsor Role: collaborator

Veterans Medical Research Foundation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Charles Ginsberg, MD

Role: CONTACT

cginsberg@ucsd.edu

8585528585 ext. 2243

Joachim Ix, MD

Role: CONTACT

joeix@ucsd.edu

8585528585 ext. 7528

References

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.

Reference Type: BACKGROUND

PMID: 21292817 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10648498 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27448672 (View on PubMed)

Other Identifiers

VAH170095

Identifier Type: -

Identifier Source: org_study_id