Vascular Effects of Mineralocorticoid Receptor Antagonism in Kidney Disease

NCT02497300 | Completed Phase 2 Results

• 1 other identifier: F140508008
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Vascular endothelial dysfunction increases cardiovascular (CV) risk and contributes to the progression of chronic kidney disease (CKD). Mineralocorticoid receptor (MR) antagonists have been shown to improve endothelial function, as well as decrease CV mortality and proteinuria. The specific biochemical pathways that produce these pharmacological effects for MR antagonists, however, are poorly understood. This study investigates the effect of MR antagonism on endothelial function in patients with moderate (stage III) CKD using a randomized, controlled trial. Three specific aims are proposed: Aim 1: To determine if spironolactone improves endothelial function as compared to amiloride in patients with stage III CKD; Aim 2: To determine if oxidative stress is associated with changes in endothelial function by spironolactone compared to amiloride in patients with stage III CKD; and Aim 3: To determine if endothelial dysfunction contributes to albuminuria in patients with stage III CKD. The clinical relevance is to improve understanding of the mechanisms of kidney function decline in CKD in order to develop interventions to delay or prevent dialysis, which would translate into alleviating patient suffering, caregiver burden, and health care costs.

Conditions

Chronic Kidney Disease; Albuminuria

Keywords

Mineralocorticoid Receptor Antagonists; Mineralocorticoid Effects

Outcome Measures

Primary Outcomes (3)

• Difference in 24 Hour Ambulatory Systolic Blood Pressure

  The study was not able to meet its recruitment goal, and participant numbers were too low to test the intended primary outcome of "Difference in percent change of ultrasound-guided flow-mediated dilation between 6 weeks of spironolactone vs. 6 weeks of amiloride." The change in 24hr ABPM systolic BP (Baseline - 6 week) is reported here.

  6 weeks

• Change in Oxidative Stress as Measured by Urine Levels of F2-isoprostanes

  Difference in level of urine 8-iso-prostaglandin-F2-alpha per mg of creatinine levels between 6 weeks of spironolactone vs. 6 weeks of amiloride.

  6 weeks

• Change in Albuminuria

  Change of the urine albumin-to-creatinine ratio (baseline - post-study med) after 6 weeks of spironolactone vs. 6 weeks of amiloride.

  6 weeks

Secondary Outcomes (2)

• Change in Serum Potassium

  6 weeks

• Change in Serum Creatinine (Baseline - Post-medication)

  6 weeks

Study Arms (2)

Spironolactone

EXPERIMENTAL

Participants will be randomized to spironolactone 25mg daily for the 1st or 2nd 6 week treatment period.

Drug: Spironolactone

Amiloride

ACTIVE COMPARATOR

Participants will be randomized to amiloride 5mg daily for the 1st or 2nd 6 week treatment period.

Drug: Amiloride

Interventions

Spironolactone DRUG

Spironolactone

Amiloride DRUG

Amiloride

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (18-65 years of age)
• CKD (eGFR 25-60 mL/min/1.73m2) with urine albumin-to-creatinine ratio \> 30 mg/g
• CKD (eGFR \> 60 mL/min/1.73m2) with urine albumin-to-creatinine ratio ≥ 300 mg/g

You may not qualify if:

• Severe hypertension (HTN) (office BP ≥ 160/100 mm Hg)
• Hypotension (office BP \< 110/70 mm Hg)
• Serum potassium \> 5 milliequivalent/L
• History of arrhythmia, including atrial fibrillation
• Pregnant or breast feeding woman
• Diabetes mellitus (DM) type 1
• Diabetes mellitus type 2 with glycosylated hemoglobin ≥ 6.5%
• Dementia or cognitive impairment prohibiting consent
• History of ischemic stroke, unstable angina, or myocardial infarction within the past 6 months
• Allergy or intolerance to spironolactone or amiloride
• Use of an MR antagonist or an epithelial sodium channel blocking medication within the last month
• Known primary aldosteronism or renal artery stenosis

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Hypertension Research Clinic at UAB

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Albuminuria

Interventions

Spironolactone; Amiloride

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; Proteinuria; Urination Disorders; Urological Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Eric Judd
• Organization: University of Alabama at Birmingham

ejudd@uab.edu

205 934-9509

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: July 8, 2015
• First Posted: July 14, 2015
• Study Start: March 1, 2015
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2021
• Last Updated: December 21, 2022
• Results First Posted: December 21, 2022

Record last verified: 2022-11

Locations

US (1)