Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03956576 |
| Other study ID # |
AC18094 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 4, 2020 |
| Est. completion date |
December 14, 2022 |
Study information
| Verified date |
January 2023 |
| Source |
University of Edinburgh |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Chronic kidney disease (CKD) affects 8-16% of the world's population, and is independently
associated with cardiovascular disease (CVD). As renal function declines, rates of major
adverse cardiovascular events, cardiovascular and all-cause mortality increase. In addition
to hypertension, increased arterial stiffness is characteristic of CKD, a marker of CVD risk,
and an independent predictor of mortality in CKD patients. The endothelium is an important
regulator of arterial stiffness, and endothelial dysfunction is a feature of CKD and a
predictor of CVD. Current treatment of CKD is limited and aims to reduce blood pressure and
proteinuria through the use of angiotensin converting enzyme (ACE) inhibitors or angiotensin
receptor blockers (ARB). However, many patients still progress to end-stage renal failure and
often these patients die as a result of CVD.
A novel peptide, apelin, is proposed to be a potential treatment for CKD, with additional
cardiovascular benefits. The AlPaCKa study investigators will carry out forearm blood flow
and renal clearance studies in 25 patients with CKD and 25 matched healthy volunteers to
determine the effects of apelin on cardiovascular and renal parameters. It is hoped apelin
will be confirmed as a potential future treatment for CKD.
Description:
The apelins are a family of peptides whose most abundant isoform is [Pyr1]apelin-13. This
binds to a single G protein coupled receptor known as 'APJ', which is widely expressed
particularly in endothelium and cardiomyocytes. Apelin is the most powerful inotropic agent
discovered to date, and apelin infusion into healthy humans leads to endothelium-dependent
vasodilatation and BP lowering. Given its vasodilatory and inotropic effects, apelin is being
investigated as a novel therapy for heart failure and pulmonary arterial hypertension, both
of which are features of CKD. The apelin/APJ system is widely expressed in the human kidney
(endothelium, smooth muscle cells, glomeruli) with a predominance in the renal medulla. It is
recognised to have a role in fluid homeostasis, and apelin infusion in rodents leads to a
dose-dependent diuresis but it is difficult to discriminate how much of this is due to renal
vasodilatation as opposed to a direct tubular effect. However, it has been shown that apelin
counteracts the antidiuretic effect of vasopressin at the tubular level. Evidence therefore
suggests that apelin could have additional cardioprotective effects in CKD and could promote
natriuresis and diuresis. To date there are no clinical studies of the actions of apelin in
the kidney in health or CKD, or its effect on systemic haemodynamics in CKD.
Twenty-five patients with CKD and 25 matched healthy volunteers will undergo forearm blood
flow studies with acetylcholine, sodium nitroprusside and apelin to determine the local
haemodynamic effects of apelin in CKD, specifically the effects on endothelial function. The
same subjects will then complete two renal clearance studies during systemic apelin / placebo
infusion (randomised and double-blinded), by standard renal para-aminohippurate and inulin
clearance techniques. Blood and urine samples will be collected every 30 minutes. This will
allow the effects of apelin on renal function, renal blood flow, proteinuria, natriuresis and
diuresis to be demonstrated. Cardiovascular effects will be determined by systemic
bioimpedance measures and pulse wave velocity. This study aims to open a new area of clinical
research with apelin.
