Assessment of Longitudinal Changes in Endothelial Function and Oxidative Stress in Normotensive Patients With ADPKD

NCT03493802 | Completed

• 1 other identifier: 17-005944
• Study Type: observational
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether patients with autosomal dominant polycystic kidney disease (ADPKD) present with abnormal endothelial function, increased levels of NOX4 activity and mitochondrial abnormalities, contributing to oxidative stress from early stages that correlate with disease severity.

Conditions

Autosomal Dominant Polycystic Kidney Disease

Keywords

ADPKD; Endothelial dysfunction; Oxidative stress; NADPH oxidase 4 (NOX4); Mitochondria

Outcome Measures

Primary Outcomes (6)

• Assessment of endothelial function by Peripheral Artery Tonometry (PAT)

  PAT is a novel non-invasive technology which records volume changes in the microcirculation of the digits in response to hyperemia, to measure peripheral vasodilator response as a measure for endothelial dysfunction.

  18 months

• NADPH oxidase 4 (NOX4) expression/activity

  Determined by ELISA from plasma and urine

  18 months

• Mitochondrial DNA copy number

  Plasma and urine levels of the mitochondria encoded genes cytochrome-c oxidase-3 (COX3) and nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit-1 (ND1) determined by quantitative real-time polymerase chain reaction

  18 months

• Total kidney volume (TKV)

  Determined by MRI

  18 months

• Renal blood flow (RBF)

  Determined by MRI

  18 months

• Glomerular filtration rate (GFR)

  Determination of iothalamate clearance

  18 months

Study Arms (2)

Patients with a previous diagnosis of ADPKD

Patients that have been diagnosed with ADPKD and meet the study's inclusion criteria

Healthy individuals as controls

Age and gender-matched healthy controls

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Male and female patients with a previous diagnosis of ADPKD that meet the inclusion criteria. In addition, patients will be matched 2:1 to age and gender healthy controls. Exclusion criteria are listed in for ADPKD patients and healthy controls.

You may qualify if:

• ADPKD Patients:
• ADPKD (based on Ravine et al. criteria)
• Class 1 B-D according to our imaging classification
• Male and female subjects 18 - 40 years of age, inclusive
• Estimated GFR\> 60 mL/min/m2 (CKD-Epi equation)
• Systolic BP≤130mmHg without taking HTN medications
• Ability to provide written, informed consent
• Healthy controls:
• Male and female subjects 18 - 40 years of age, inclusive
• estimated GFR\> 60 mL/min/m2 (CKD-EPI equation)
• Systolic BP≤130mmHg without taking HTN medications
• Ability to provide written, informed consent

You may not qualify if:

• ADPKD Patients:
• Class 2 according to our imaging classification
• Concomitant systemic disease in the kidney (e.g. lupus, hepatitis B or C, amyloidosis)
• Diabetes mellitus (fasting glucose \> 126 mg/dL or treatment with insulin or oral hypoglycemics).
• Predicted urine protein excretion in urinalysis \>1 g/24 hrs
• Abnormal urinalysis suggestive of concomitant glomerular disease
• Subjects having contraindications to, or interference with MRI assessments. \[For example: ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, large abdominal/back tattoos, etc\].
• Female subjects that are pregnant
• Healthy controls:
• Previous personal or family history of kidney disease
• Concomitant systemic disease in the kidney (e.g. lupus, hepatitis B or C, amyloidosis)
• Diabetes mellitus (fasting glucose \> 126 mg/dL or treatment with insulin or oral hypoglycemics).
• Presence of proteinuria
• Abnormal urinalysis suggestive glomerular disease
• Subjects having contraindications to, or interference with MRI assessments. \[For example: ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, large abdominal/back tattoos, etc\]

Sponsors & Collaborators

• Mayo Clinic: lead
• University of Kansas Medical Center: collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant

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

Study Officials

• Maria V Irazabal, M.D., Ph.D.

  Mayo Translational PKD Center, Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 23, 2018
• First Posted: April 11, 2018
• Study Start: November 1, 2017
• Primary Completion: January 17, 2020
• Study Completion: January 17, 2020
• Last Updated: May 6, 2024

Record last verified: 2024-05

Locations

US (1)