Evaluating the Effect of Standard-of-care Erythropoiesis-stimulating Agents on Forearm Blood Flow in Nondialysis-dependent Subjects With Anaemia Associated With Chronic Kidney Disease.

NCT02987465 | Completed

• 1 other identifier: OPERA-CKD (AO94224)
• Study Type: observational
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

In people diagnosed with chronic kidney disease (CKD) anaemia is a common problem and is often treated with EPO (Erythropoietin). One form of EPO used is Darbepoetin (Aranesp®). EPO is safe to use but it has been associated with a rise in blood pressure (BP) in some individuals. The reasons for this are not clear. To try to explain this, this study will look at how EPO affects certain substances in the blood that influence how blood vessels contract and relax. This will be conducted by infusing small amounts of Acetylcholine, BQ123 and Noradrenaline into the arm vessels of volunteers using an established method called Forearm blood flow (plethysmography). Volunteers recruited for this study will include CKD patients undergoing therapy with Darbepoetin as part of their normal NHS care as well as healthy people not on treatment, who will act as controls. This is an observational pilot study of changes in physiology before and after Darbepoetin. It will provide valuable data for a later study comparing Darbepoetin to novel agents which work via different pathways to treat anaemia.

Conditions

Cardiovascular Diseases; Chronic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• Response to intra-arterial acetylcholine

  Change in forearm blood flow responses as measured by venous occlusion plethysmography, in response to intra-arterial acetylcholine

  CKD patients: Measured at baseline and at the end of the 6 week treatment period

Secondary Outcomes (7)

• Response to intra-arterial Noradrenaline

  CKD patients: Measured at baseline before treatment with Darbepoetin and then at the end of the 6 week treatment period with Darbepoetin

• Response to intra-arterial BQ123

  CKD patients: Measured at baseline before treatment with Darbepoetin and then at the end of the 6 week treatment period with Darbepoetin

• Change in mean arterial blood pressure

  CKD patients: Measured at baseline before treatment with Darbepoetin and then at the end of the 6 week treatment period with Darbepoetin

• Changes in Arterial stiffness

  CKD patients: Measured at baseline before treatment with Darbepoetin and then at the end of the 6 week treatment period with Darbepoetin

• Correlations between individual challenge agent

  CKD patients: Measured at baseline before treatment with Darbepoetin and then at the end of the 6 week treatment period with Darbepoetin

Study Arms (2)

Chronic Kidney Disease patients

Up to 12 patients with anaemia associated with CKD.

Drug: Darbepoetin Alfa; Drug: Acetylcholine; Drug: Noradrenaline; Drug: BQ 123

Healthy Volunteers

Up to 12 healthy subjects will be recruited such that age and gender are similar to the CKD patients. These subjects will be recruited as negative controls for a baseline assessment of healthy physiology. These subjects will not be treated with Darbepoetin.

Drug: Acetylcholine; Drug: Noradrenaline; Drug: BQ 123

Interventions

Darbepoetin Alfa DRUG

Darbepoetin is not a study drug and is prescribed as part of routine treatment of anaemia in CKD1. Darbepoetin is licensed for use for the treatment of anaemia in the context of CKD. It will be provided as part of the standard clinical care of the renal patients in this study. Healthy Volunteers will not be treated with Darbepoetin.

Chronic Kidney Disease patients

Acetylcholine DRUG

Acetylcholine is being used as a challenge agent in this study and assesses NO-mediated vasodilation

Chronic Kidney Disease patients; Healthy Volunteers

Noradrenaline DRUG

Noradrenaline is being used as a challenge agent in this study and is an endogenous a1 adrenoceptor agonist

Chronic Kidney Disease patients; Healthy Volunteers

BQ 123 DRUG

BQ 123 is being used as a challenge agent in this study and is an (Endothelin A) ETA receptor agonist.

Chronic Kidney Disease patients; Healthy Volunteers

Eligibility Criteria

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

Study Population

Up to 12 patients with anaemia associated with chronic kidney disease (CKD). Up to 12 healthy volunteers.

You may qualify if:

• Provided written informed consent to participate
• Be aged 18 years or over
• Clinically suitable for EPO (Darbepoetin) therapy as part of routine NHS standard of care for anaemia due to chronic kidney disease (CKD)
• No prior EPO treatment within the preceding 12 months
• Palpable brachial artery
• Provided written informed consent to participate
• Aged 18 years or over
• Blood pressure \<140/90
• Normal haematology and renal function (defined as a normal creatinine and eGFR measured at any time in the last 6 months or at screening)
• Not on any regular prescribed medication
• Palpable brachial artery

You may not qualify if:

• Kidney transplant: Planned living-related kidney transplant within 26 weeks
• Patients on PDE5 inhibitors, alpha blockers, or nitrates (other than PRN GTN), unless they can be omitted until after the forearm study on the day of the visit
• MI or acute coronary syndrome in the preceding ≤ 4 weeks prior to screening
• Stroke or transient ischemic attack in the preceding ≤ 4 weeks prior to screening
• Known clinical diagnosis of Heart failure: NYHA Class III-IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
• Clinic Blood pressure: sustained BP \> 170/100 mm Hg (on repeated measurements)
• Pregnancy - Non-sterilised, pre-menopausal women will undergo urinary beta-HCG testing at every visit and be given advice on contraceptive use in the PIS.
• Any condition which, in the opinion of the investigator, precludes enrolment
• Undergoing investigation for any serious medical condition

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Addenbrooke's Hospital

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Some serum samples will be collected and stored for future analysis as part of the OPERA-CKD study.

MeSH Terms

Conditions

Cardiovascular Diseases; Renal Insufficiency, Chronic

Interventions

Darbepoetin alfa; Acetylcholine; Norepinephrine; cyclo(Trp-Asp-Pro-Val-Leu)

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

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins; Biogenic Amines; Amines; Organic Chemicals; Ethanolamines; Amino Alcohols; Alcohols; Biogenic Monoamines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Joseph Cheriyan, MBCHB, MA, FRCP

  Cambridge University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Physician & Clinical Pharmacologist/Assoc Lecturer

Study Record Dates

• First Submitted: November 28, 2016
• First Posted: December 9, 2016
• Study Start: February 20, 2017
• Primary Completion: May 21, 2018
• Study Completion: May 21, 2018
• Last Updated: February 7, 2024

Record last verified: 2024-02

Locations

GB (1)