Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

NCT01853553 | Completed Phase 3 Results

• 2 other identifiers: 13-1440R01DK097081
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed research will determine the effectiveness of blocking aldosterone for improving the health and function of arteries in patients with autosomal dominant polycystic kidney disease (ADPKD). The study also will provide insight into how blocking aldosterone improves artery health by determining the physiological mechanisms (biological reasons) involved. Overall, the proposed research will provide important new scientific evidence upon which physicians can base recommendations to patients with ADPKD to decrease risk of developing cardiovascular diseases.

Conditions

ADPKD

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Flow Mediated Dilation at 6 Months.

  FMD will be determined using high-resolution ultrasonography

  Baseline and 6 months.

Secondary Outcomes (1)

• Change From Baseline in Vascular Stiffness at 6 Months.

  Baseline and 6 months

Other Outcomes (1)

• Change in Circulating Markers of Oxidative Stress at 6 Months.

  Baseline and 6 months.

Study Arms (2)

Spironolactone

EXPERIMENTAL

Active arm

Drug: Spironolactone

Sugar Pill

PLACEBO COMPARATOR

Placebo

Drug: Sugar pill

Interventions

Spironolactone DRUG

Blood pressure medication.

Spironolactone

Sugar pill DRUG

Placebo.

Sugar Pill

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 20-55 years;
• Adults with ADPKD diagnosis based on Ravine criteria aged ≥ 30 years
• Estimated glomerular filtration rate ≥ 60 ml/min/1.73m2
• Hypertension defined as a systolic BP \> 130 mm Hg and/or diastolic BP \> 80 mmHg based on 3 separate measurements within the past year and currently on a minimum dose of an angiotensin converting enzyme inhibitor (minimum dose 10 mg P.O qd) or angiotensin receptor blocker (i.e., Losartan 25 mg P.O qd)
• If using antioxidants and/or omega-3 fatty acids, must discontinue 4 weeks prior to participation
• Free from alcohol dependence or abuse
• Mini-mental state examination score ≥ 24; ability to provide informed consent
• BMI \< 40 kg/m2 (FMD measurements can be inaccurate in severely obese patients)
• Not taking medications that interact with agents administered during experimental sessions (e.g., sildenafil interacts with nitroglycerin)

You may not qualify if:

• Average serum potassium \>5.5 millequivalents or any single serum potassium \> 6.0 millequivalents within the previous 6 months
• Receiving an aldosterone antagonist within the previous 6 months
• Use of a potassium sparing diuretic or any other drug that could contribute to hyperkalemia
• Uncontrolled hypertension
• Current smokers or history of smoking in the past 12 months
• History of liver disease
• History of heart failure (EF \< 35%)
• History of hospitalizations within the last 3 months
• Active infection or antibiotic therapy
• Warfarin use
• Immunosuppressive therapy within the last year
• Pregnancy

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

UColorado

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• Nowak KL, Gitomer B, Farmer-Bailey H, Wang W, Malaczewski M, Klawitter J, You Z, George D, Patel N, Jovanovich A, Chonchol M. Mineralocorticoid Antagonism and Vascular Function in Early Autosomal Dominant Polycystic Kidney Disease: A Randomized Controlled Trial. Am J Kidney Dis. 2019 Aug;74(2):213-223. doi: 10.1053/j.ajkd.2018.12.037. Epub 2019 Feb 23.

  PMID: 30803706 DERIVED

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant

Interventions

Spironolactone; Sugars

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Carbohydrates

Limitations and Caveats

A potential limitation to the study is a relatively small sample size; however, we were appropriately powered to detect an improvement in the primary endpoint given expected vascular endothelial function at the time the trial was designed.

Results Point of Contact

• Title: Dr. Michel Chonchol
• Organization: University of Colorado

Michel.Chonchol@ucdenver.edu

303-724-7796

Study Officials

• Michel B Chonchol, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2013
• First Posted: May 15, 2013
• Study Start: July 1, 2013
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: August 20, 2019
• Results First Posted: August 20, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)