Apelin as a Potential Treatment for Chronic Kidney Disease

NCT03956576 | Completed

• 1 other identifier: AC18094
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Kidney Diseases; Cardiovascular Diseases; Endothelial Dysfunction

Outcome Measures

Primary Outcomes (2)

• Change in forearm blood flow

  Venous occlusion plethysmography

  1 hour

• Change in renal blood flow

  Para-aminohippurate clearance study

  4 hours

Secondary Outcomes (6)

• Change in arterial stiffness

  1 hour

• Change in natriuresis

  4 hours

• Change in diuresis

  4 hours

• Change in blood pressure

  4 hours

• Change in proteinuria

  4 hours

Study Arms (2)

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.

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.

Other: [Pyr]apelin-13

Interventions

[Pyr]apelin-13 OTHER

Peptide \[Pyr\]apelin-13 infusion

Chronic Kidney Disease patients; Healthy volunteers

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Age \<18 years
• Diabetes mellitus
• Overt cardiovascular disease
• Blood pressure \>160/100mmHg
• Estimated GFR of \<15ml/min/1.73m2
• Renal transplant recipients
• 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

Sponsors & Collaborators

• University of Edinburgh: lead
• Kidney Cancer UK: collaborator

Study Sites (1)

Clinical Research Centre, Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39402039 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Cardiovascular Diseases

Interventions

apelin 13, Pyr(1)-

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Neeraj Dhaun, PhD

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2018
• First Posted: May 20, 2019
• Study Start: February 4, 2020
• Primary Completion: December 14, 2022
• Study Completion: December 14, 2022
• Last Updated: January 27, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)