Characterization of the Nrf2 Response in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Study Purpose

The purpose of this study is to characterize oxidative stress and the Nrf2 antioxidant response in early stages of Autosomal Dominant Polycystic Kidney Disease (ADPKD), while identifying candidate biomarkers.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Yes
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Observational
Eligible Ages 18 Years - 30 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria (ADPKD Subjects):

  • - ADPKD (based on Ravine et al.
criteria)
  • - Class 1 B-E according to our imaging classification.
  • - Male and female subjects 18 - 30 years of age, inclusive.
  • - Estimated GFR> 60 mL/min/m2 (CKD-EPI equation) - Ability to provide written, informed consent.
Exclusion Criteria (ADPKD Subjects):
  • - 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.
Inclusion Criteria (Healthy Subjects):
  • - Male and female subjects 18 - 30 years of age, inclusive.
  • - Estimated GFR> 60 mL/min/m2 (CKD-EPI equation) - Ability to provide written, informed consent.
Exclusion Criteria (Healthy Subjects):
  • - 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 Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04344769
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Mayo Clinic
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Maria V. Irazabal, M.D., Ph.D
Principal Investigator Affiliation Mayo Translational PKD Center, Mayo Clinic
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, NIH
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Autosomal Dominant Polycystic Kidney Disease
Study Website: View Trial Website
Additional Details

Intracellular Reactive Oxygen Species (ROS) concentration is a major determinant of cellular fate and is finely regulated by the cell's antioxidant systems. While low levels of ROS are required for pro-survival signaling, cell proliferation, growth, and energy metabolism, the excess of ROS or oxidative stress leads to inflammation, cell death, and disease/injury progression. Indeed, oxidative stress is commonly observed in several renal diseases including ADPKD. On the other hand, a surplus of antioxidants will not only neutralize ROS, but may result in the antithesis of oxidative stress, which is known as reductive stress. The Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor that integrates cellular stress signals and responds by regulating the expression of several antioxidant proteins. Activation of the Nrf2-mediated antioxidant defense pathway enhances ROS detoxification, conferring a more reduced intracellular environment that can promote cell survival and proliferation, a distinctive feature in ADPKD that underlies cyst formation and enlargement. Therefore, a better characterization of ROS levels and antioxidant response in ADPKD patients would allow development of more specific and effective therapies, while providing additional related biomarkers. The investigators broad objective is to characterize oxidative stress and the Nrf2 antioxidant response in early stages of ADPKD, while identifying candidate biomarkers. Participants in this study will have a blood and a urine sample collected to determine biomarkers of oxidative status and antioxidant response to study redox balance at early stages of the disease. In addition, an abdominal MRI will be performed to determine patient's total kidney volume (TKV).

Arms & Interventions

Arms

: 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

Interventions

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Mayo Clinic in Rochester, Rochester, Minnesota

Status

Recruiting

Address

Mayo Clinic in Rochester

Rochester, Minnesota, 55905

Site Contact

[email protected]