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

Autosomal Dominant Polycystic Kidney Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04344769
• Other study ID #: 17-008806
• Secondary ID: R21DK118391
• Status: Recruiting
• Start date: October 4, 2019
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: Mayo Clinic
• Contact: Ahmed Abdelfattah
• Email: Abdelfattah.Ahmed[@]mayo.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthrogryposis
• Autosomal Dominant Polycystic Kidney Disease
• Kidney Diseases
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of Oxidative Status	Determination of common biomarkers of oxidative damage including but not limited to: 8-oxodeoxyguanosine, F2-isoprostanes, from urine and plasma samples	Baseline
Primary	Assessment of Antioxidant Response	Determination of antioxidants including but not limited to: Heme Oxygenase 1 (HO-1), Superoxide dismutase (SOD), catalase, glutathione reductase (GSR), glutathione peroxidase (GPx), and NAD(P)H dehydrogenase [quinone] 1 (NOQ1), glutathione, Nrf2 from urine and plasma samples	Baseline
Primary	Total kidney volume (TKV)	Determined by MRI	Baseline
Secondary	Assessment of Kidney Injury	Determination of kidney injury biomarkers including but not limited to: Kidney Injury Molecule 1 (KIM-1), Neutrophil gelatinase-associated lipocalin (NGAL), Monocyte chemotactic protein-1 (MCP-1), Transforming growth factor-ß1 (TGF-ß1),	Baseline