Autosomal Dominant Polycystic Kidney DiseaseNCT03493802
Assessment of Longitudinal Changes in Endothelial Function and Oxidative Stress in Normotensive Patients With ADPKD
An observational study of Autosomal Dominant Polycystic Kidney Disease, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Autosomal Dominant Polycystic Kidney Disease
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2017to 17 Jan 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
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.
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Show all 16Show fewer
- 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]
- Female subjects that are pregnant
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assessment of Longitudinal Changes in Endothelial Function and Oxidative Stress in Normotensive Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) - A Pilot Study
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.
Read the detailed description
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic and the fourth cause of end-stage renal disease (ESRD) in adults worldwide. Cardiovascular diseases are the most important non-cystic complications and continue to be the leading cause of premature mortality in these patients. Hypertension (HTN) is present in approximately 50% of the patients at early stages, and increases to nearly 100% at ESRD. Furthermore, HTN contributes to the underlying renal disease progression. Nitric oxide (NO) associated endothelium-dependent vasorelaxation has been shown to be impaired in small subcutaneous resistance vessels from patients with ADPKD before the development of HTN. However, the principal contributors to vascular dysfunction remain unclear.
The investigators broad objective is to evaluate the presence and extent of endothelial dysfunction and its association with oxidative stress in young normotensive patients with ADPKD, with the long term goal of timely intervention to slow the progression of the disease in these patients.
Participants in this study will have their endothelial function assessed using a non-invasive technique, peripheral arterial tonometry (PAT), which has been shown to be a useful, highly reproducible, and non-operator dependent method for non-invasive assessment of vascular health. The investigators will assess longitudinal changes in endothelial function using PAT with the intention of establishing if this methodology offers the potential of non-invasive measures of early vascular disease in young normotensive patients with ADPKD. Biochemical markers of endothelial dysfunction will be assessed concomitantly. In addition, the investigators will assess oxidative stress levels in these patients, with the intention of determining the association with endothelial dysfunction.
- Keywords
- ADPKD, Endothelial dysfunction, Oxidative stress, NADPH oxidase 4 (NOX4), Mitochondria
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 18 months
NADPH oxidase 4 (NOX4) expression/activity
Determined by ELISA from plasma and urine
Measured: 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
Measured: 18 months
Total kidney volume (TKV)
Determined by MRI
Measured: 18 months
Renal blood flow (RBF)
Determined by MRI
Measured: 18 months
Glomerular filtration rate (GFR)
Determination of iothalamate clearance
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2018
- Study start1 Nov 2017
- Primary completion17 Jan 2020
- Study completion17 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autosomal Dominant Polycystic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- University of Kansas Medical Center
- Responsible party
- Principal investigator, Maria V. Irazabal Mira, Mayo Clinic
- Investigators
- Maria V Irazabal, M.D., Ph.D., Principal investigator, Mayo Translational PKD Center, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03493802
- Sponsor's protocol ID
- 17-005944
- Status last verified
- May 2024
- First submitted
- 23 Mar 2018
- Last updated
- 6 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Longitudinal Changes in Endothelial Function and Oxidative Stress in Normotensive Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) - A Pilot Study
- ClinicalTrials.gov ID
- NCT03493802
- Acronym / sponsor ID
- 17-005944
- Keywords
- ADPKD, Endothelial dysfunction, Oxidative stress, NADPH oxidase 4 (NOX4), Mitochondria
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- University of Kansas Medical Center
- Study start
- 1 Nov 2017 (actual)
- Primary completion
- 17 Jan 2020 (actual)
- Study completion
- 17 Jan 2020 (actual)
- First posted
- 11 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic and the fourth cause of end-stage renal disease (ESRD) in adults worldwide. Cardiovascular diseases are the most important non-cystic complications and continue to be the leading cause of premature mortality in these patients. Hypertension (HTN) is present in approximately 50% of the patients at early stages, and increases to nearly 100% at ESRD. Furthermore, HTN contributes to the underlying renal disease progression. Nitric oxide (NO) associated endothelium-dependent vasorelaxation has been shown to be impaired in small subcutaneous resistance vessels from patients with ADPKD before the development of HTN. However, the principal contributors to vascular dysfunction remain unclear.
The investigators broad objective is to evaluate the presence and extent of endothelial dysfunction and its association with oxidative stress in young normotensive patients with ADPKD, with the long term goal of timely intervention to slow the progression of the disease in these patients.
Participants in this study will have their endothelial function assessed using a non-invasive technique, peripheral arterial tonometry (PAT), which has been shown to be a useful, highly reproducible, and non-operator dependent method for non-invasive assessment of vascular health. The investigators will assess longitudinal changes in endothelial function using PAT with the intention of establishing if this methodology offers the potential of non-invasive measures of early vascular disease in young normotensive patients with ADPKD. Biochemical markers of endothelial dysfunction will be assessed concomitantly. In addition, the investigators will assess oxidative stress levels in these patients, with the intention of determining the association with endothelial dysfunction.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Assessment of endothelial function by Peripheral Artery Tonometry (PAT)
Time frame: 18 months
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.
NADPH oxidase 4 (NOX4) expression/activity
Time frame: 18 months
Determined by ELISA from plasma and urine
Mitochondrial DNA copy number
Time frame: 18 months
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
Total kidney volume (TKV)
Time frame: 18 months
Determined by MRI
Renal blood flow (RBF)
Time frame: 18 months
Determined by MRI
Glomerular filtration rate (GFR)
Time frame: 18 months
Determination of iothalamate clearance
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2024.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maria V Irazabal, M.D., Ph.D. principal investigator
Mayo Translational PKD Center, Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Autosomal Dominant Polycystic Kidney Disease, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of endothelial function by Peripheral Artery Tonometry (PAT) (time frame: 18 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2024; AzTrials last refreshed its copy on 31 Oct 2026.