A Study to Evaluate Homocysteine Metabolism and Endothelial Function in ADPKD

Autosomal Dominant Polycystic Kidney Disease Clinical Trial

— HCY  

Official title:

Role of Homocysteine Metabolism, Endothelial Function and Microvascular Rarefaction on Renal Disease Severity and Progression in ADPKD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05193981
• Other study ID #: 20-005312
• Secondary ID: 1R01DK128017-01
• Status: Recruiting
• Start date: September 14, 2021
• Est. completion date: June 2026

Study information

• Verified date: April 2024
• Source: Mayo Clinic
• Contact: Ahmed Abdelfattah
• Phone: 507-266-2108
• Email: Abdelfattah.Ahmed[@]mayo.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to assess homocysteine metabolism and systemic endothelial function at the early stages of the disease and determine the prognostic value of homocysteine, related metabolites, and markers of endothelial function and injury to estimate renal disease severity and progression in patients with early Autosomal Dominant Polycystic Kidney Disease (ADPKD).

Description:

ADPKD is a devastating systemic disorder characterized by progressive development and enlargement of bilateral renal cysts, often leading to renal failure. Disease severity and progression vary widely among patients. Large phenotypic variability, incomplete understanding of underlying mechanisms, and lack of suitable biomarkers challenge potential therapies' identification, implementation, and evaluation.

In ADPKD, systemic endothelial dysfunction (ED), characterized by an imbalance between vasodilating (particularly nitric oxide, NO) and vasoconstricting substances, develops early and correlates with renal disease severity. It has been previously associated with decreased NO availability, but NO abnormalities' mechanisms are still poorly understood. Endothelium-dependent, NO-mediated vasodilation is impaired in subjects with hyperhomocysteinemia, suggesting that NO availability is decreased in these subjects. Increased plasma levels of homocysteine have been reported in patients with ADPKD and preserved kidney function, likely contributing to a reduction in NO bioavailability. The mechanisms underlying increased homocysteine in ADPKD are not known. Furthermore, whether systemic endothelial function and injury or homocysteine levels can predict renal disease severity and progression in patients is unknown.

The investigators' broad objective is to assess homocysteine metabolism and systemic endothelial function at the early stages of the disease and determine the prognostic value of homocysteine, related metabolites, and markers of endothelial function and injury to estimate renal disease severity and progression in patients with early ADPKD.

Participants in this study will have a blood and a urine sample collected to determine biomarkers of oxidative stress, endothelial function and injury, homocysteine, and related metabolite levels. In addition, peripheral arterial tonometry (PAT) will determine systemic endothelial function, and an abdominal MRI will be performed to determine the patient's total kidney volume (TKV).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 40 Years

Eligibility

Inclusion Criteria:

• Male and Female subjects, 15-40 years of age, inclusive

• Previous diagnosis of ADPKD (Based on Ravine et al. criteria)

• Class 1 according to imaging classification

• Estimated GFR>70 mL/min/1.73m^2(CKD-EPI)

• Ability to provide written, informed consent.

Exclusion Criteria:

• Class 2 according to imaging classification

• A concomitant systemic disease affecting the kidney

• Diabetes mellitus

• Predicted urine protein excretion in urinalysis >1 g/24 hrs

• Subjects having contraindications to or interference with MRI assessments

• Patients that are part of an interventional study or taking tolvaptan

• Female subjects that are pregnant

Related Conditions & MeSH terms

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

Locations

Country	Name	City	State
United States	Mayo Clinic	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	Change in height adjusted Total kidney volume (htTKV)	TKV determined by MRI	Baseline to 24 months
Primary	Baseline endothelial function, homocysteine and related metabolite levels as predictors of change in TKV	Endothelial function determined by PAT and biochemical markers, TKV determined by MRI	Baseline to 24 months
Secondary	Change in systemic endothelial function	Endothelial function determined by PAT	Baseline to 24 months
Secondary	Change in biochemical markers related to endothelial function and injury	Determined by ELISA and/or biochemical assays	Baseline to 24 months
Secondary	Change in homocysteine and related metabolite levels	Determined by 1HNMR, Mass spect, ELISA	Baseline to 24 months
Secondary	Change in Renal blood flow (RBF)	Determined by MRI	Baseline to 24 months
Secondary	Change in estimated Glomerular filtration rate (GFR)	eGFR determined by CKD-epi equation	Baseline to 24 months
Secondary	NADPH oxidase 4 (NOX4) expression/activity	Determined by ELISA	Baseline to 24 months