Phosphate Microvascular Study
The Effects of Phosphate on Microvascular Function
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.
調査の概要
詳細な説明
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.
研究の種類
入学 (予想される)
段階
- 適用できない
連絡先と場所
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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).
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：診断
- 割り当て：ランダム化
- 介入モデル：クロスオーバー割り当て
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
介入なし：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.
|
|
|
プラセボコンパレーター：Intervention
Participants will take a placebo instead of standard care with a phosphate binder, for 2 weeks.
|
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.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
% Change in flux of blood after skin heating to 44 C as measured using laser-Doppler flowmtery.
時間枠：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)
|
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)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in capillary count seen post occlusion from pre occlusion, as determined by nail-fold capillaroscopy.
時間枠：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)
|
Participants will undergo nail fold capillaroscopy using a CapiScope (KK Technology, Honiton United Kingdom) at baseline and then at the end of each treatment arm.
Using a capillarascope a capillary count will be made.
After measurement a BP cuff will be inflated to 200 mm Hg occlude flow to a single digit for 1 minute.
30 sec after release the count will be made again.
This change will be compared within individuals between measurements made at the completion of each arm in the study.
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.
Values at the end of each treatment arm will be compared.
|
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)
|
協力者と研究者
出版物と役立つリンク
一般刊行物
- 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.
- 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.
- 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.
研究記録日
主要日程の研究
研究開始 (予想される)
一次修了 (予想される)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- VAH170095
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
IPD 共有サポート情報タイプ
- 研究プロトコル
- 統計分析計画 (SAP)
- インフォームド コンセント フォーム (ICF)
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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