Chronic Kidney DiseasesAlPaCKaNCT03956576
Apelin as a Potential Treatment for Chronic Kidney Disease
A study testing [Pyr]apelin-13 in people with Chronic Kidney Diseases and Cardiovascular Diseases, run by University of Edinburgh at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Chronic Kidney Diseases, Cardiovascular Diseases, Endothelial Dysfunction
- What is being tested?
- [Pyr]apelin-13
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 4 Feb 2020to 14 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adults >18yrs
- Stable, non-diabetic chronic kidney disease stages 1 - 4 as defined by Kidney Disease: Improving Global Outcomes (KDIGO) 2012 classification (estimated Glomerular Filtration Rate (eGFR) >15ml/min/1.73m2)
- Clinically optimised on an angiotensin converting enzyme inhibitor / angiotensin receptor blocker, or intolerant to these agents.
Who cannot join
- Age <18 years
- Diabetes mellitus
- Overt cardiovascular disease
- Blood pressure >160/100mmHg
- Estimated GFR of <15ml/min/1.73m2
- Renal transplant recipients
Show all 13Show fewer
- Haemodialysis / peritoneal dialysis patients
- Serum albumin <30g/L
- Patients receiving tolvaptan therapy for polycystic kidney disease
- Patients not medically fit to attend for study visits
- Patients without mental capacity or willingness to provide informed consent
- History of multiple and/or severe allergic reaction to drugs (including study drugs) or food
- Patients who are pregnant or breast feeding
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Clinical Research Centre, Western General Hospital
Edinburgh, EH4 2XU
About this study
Official title: Apelin as a Potential Treatment for Chronic Kidney Disease: The AlPaCKa Study
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.
Read the detailed 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.
- Being tested
- [Pyr]apelin-13
- Medical subject headings
- Renal Insufficiency, Chronic, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[Pyr]apelin-13Other
Peptide [Pyr]apelin-13 infusion
| Study group | Role | What they receive |
|---|---|---|
| Chronic Kidney Disease patients | Active comparator | Forearm blood flow studies
- acetylcholine (7.5, 15, 30microgram/min), sodium nitroprusside (1, 2, 4microgram/min) and [Pyr1]apelin-13 (0.3, 1, 3, 10, 30, 100nmol/min). Incremental doses of each lasting 8 minutes with saline washout between drugs.
Renal clearance studies
* Two standard para-aminohippurate (PAH) / iohexol clearance studies with infusion of either apelin or placebo on each day.
* Dose of PAH / iohexol dependent on renal function. Continuous infusion lasting 6.5hours in total.
* [[Pyr1]apelin-13 infusions: 1nmol/min and 30nmol/min for 30 minutes each. Receives: Other: [Pyr]apelin-13 |
| Healthy volunteers | Active comparator | Forearm blood flow studies
- acetylcholine (7.5, 15, 30microgram/min), sodium nitroprusside (1, 2, 4microgram/min) and [Pyr1]apelin-13 (0.3, 1, 3, 10, 30, 100nmol/min). Incremental doses of each lasting 8 minutes with saline washout between drugs.
Renal clearance studies
* Two standard para-aminohippurate (PAH) / iohexol clearance studies with infusion of either apelin or placebo on each day.
* Dose of PAH / iohexol dependent on renal function. Continuous infusion lasting 6.5hours in total.
* [Pyr1]apelin-13 infusions: 1nmol/min and 30nmol/min for 30 minutes each. Receives: Other: [Pyr]apelin-13 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in forearm blood flow
Venous occlusion plethysmography
Measured: 1 hour
Change in renal blood flow
Para-aminohippurate clearance study
Measured: 4 hours
Secondary outcomes (6)
Change in arterial stiffness
Pulse wave velocity measures
Measured: 1 hour
Change in natriuresis
Urinary sodium excretion measures
Measured: 4 hours
Change in diuresis
Free water clearance measurement
Measured: 4 hours
Change in blood pressure
Blood pressure monitoring
Measured: 4 hours
Change in proteinuria
Urinary protein excretion
Measured: 4 hours
Change in chorioretinal metrics as assessed by optical coherence tomography (OCT
Optical coherence tomography measurements
Measured: 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2019
- Study start4 Feb 2020
- Primary completion14 Dec 2022
- Study completion14 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney DiseasesStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Kidney Cancer UK
- Responsible party
- Sponsor
- Investigators
- Neeraj Dhaun, PhD, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03956576
- Sponsor's protocol ID
- AC18094
- Acronym
- AlPaCKa
- Status last verified
- Jan 2023
- First submitted
- 11 Dec 2018
- Last updated
- 27 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No data to be shared
Publications
Chapman FA, Melville V, Godden E, Morrison B, Bruce L, Maguire JJ, Davenport AP, Newby DE, Dhaun N. Cardiovascular and renal effects of apelin in chronic kidney disease: a randomised, double-blind, placebo-controlled, crossover study. Nat Commun. 2024 Oct 14;15(1):8387. doi: 10.1038/s41467-024-52447-7.
PubMed 39402039
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Apelin as a Potential Treatment for Chronic Kidney Disease: The AlPaCKa Study
- ClinicalTrials.gov ID
- NCT03956576
- Acronym / sponsor ID
- AlPaCKa / AC18094
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- Kidney Cancer UK
- Study start
- 4 Feb 2020 (actual)
- Primary completion
- 14 Dec 2022 (actual)
- Study completion
- 14 Dec 2022 (actual)
- First posted
- 20 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chronic Kidney Disease patients | Active comparator | Other: [Pyr]apelin-13Forearm blood flow studies - acetylcholine (7.5, 15, 30microgram/min), sodium nitroprusside (1, 2, 4microgram/min) and [Pyr1]apelin-13 (0.3, 1, 3, 10, 30, 100nmol/min). Incremental doses of each lasting 8 minutes with saline washout between drugs. Renal clearance studies * Two standard para-aminohippurate (PAH) / iohexol clearance studies with infusion of either apelin or placebo on each day. * Dose of PAH / iohexol dependent on renal function. Continuous infusion lasting 6.5hours in total. * [[Pyr1]apelin-13 infusions: 1nmol/min and 30nmol/min for 30 minutes each. |
| Healthy volunteers | Active comparator | Other: [Pyr]apelin-13Forearm blood flow studies - acetylcholine (7.5, 15, 30microgram/min), sodium nitroprusside (1, 2, 4microgram/min) and [Pyr1]apelin-13 (0.3, 1, 3, 10, 30, 100nmol/min). Incremental doses of each lasting 8 minutes with saline washout between drugs. Renal clearance studies * Two standard para-aminohippurate (PAH) / iohexol clearance studies with infusion of either apelin or placebo on each day. * Dose of PAH / iohexol dependent on renal function. Continuous infusion lasting 6.5hours in total. * [Pyr1]apelin-13 infusions: 1nmol/min and 30nmol/min for 30 minutes each. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adults >18yrs
- Stable, non-diabetic chronic kidney disease stages 1 - 4 as defined by Kidney Disease: Improving Global Outcomes (KDIGO) 2012 classification (estimated Glomerular Filtration Rate (eGFR) >15ml/min/1.73m2)
- Clinically optimised on an angiotensin converting enzyme inhibitor / angiotensin receptor blocker, or intolerant to these agents.
Key exclusion criteria (13 listed)
- Age <18 years
- Diabetes mellitus
- Overt cardiovascular disease
- Blood pressure >160/100mmHg
- Estimated GFR of <15ml/min/1.73m2
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [Pyr]apelin-13Peptide [Pyr]apelin-13 infusion | Other | Chronic Kidney Disease patients, Healthy volunteers |
Primary outcome
Change in forearm blood flow
Time frame: 1 hour
Venous occlusion plethysmography
Change in renal blood flow
Time frame: 4 hours
Para-aminohippurate clearance study
6 secondary outcomes
Change in arterial stiffness
Time frame: 1 hour
Change in natriuresis
Time frame: 4 hours
Change in diuresis
Time frame: 4 hours
Change in blood pressure
Time frame: 4 hours
Change in proteinuria
Time frame: 4 hours
Change in chorioretinal metrics as assessed by optical coherence tomography (OCT
Time frame: 4 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2023.
- Derived from this study: PubMed 39402039Chapman FA, Melville V, Godden E, Morrison B, Bruce L, Maguire JJ, Davenport AP, Newby DE, Dhaun N. Cardiovascular and renal effects of apelin in chronic kidney disease: a randomised, double-blind, placebo-controlled, crossover study. Nat Commun. 2024 Oct 14;15(1):8387. doi: 10.1038/s41467-024-52447-7.
- Individual participant dataSharing planned: No. No data to be shared
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Neeraj Dhaun, PhD principal investigator
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing [Pyr]apelin-13 in people with Chronic Kidney Diseases and Cardiovascular Diseases, run by University of Edinburgh at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in forearm blood flow (time frame: 1 hour). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03956576, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2023.