Effect of Renin-angiotensin-system Blockade on Urinary Free Light Chains in Patients With Type 2 Diabetes Mellitus (UFLC)

August 17, 2023 updated by: Tulane University School of Medicine
The purpose of this study is to study the effect of blocking the renin angiotensin system on urinary free light chain excretion as compared to urine microalbumin creatinine ratio in subjects with type 2 diabetes. The long term goal is to assess urinary free-light chains as a biomarker of earlier detection of kidney function impairment in subjects with diabetes mellitus.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Free light chains (FLCs) are low-molecular-mass molecules (kappa and lambda light chains), which are by-products of normal immunoglobulin synthesis and are normally excreted through the kidneys. Presence of light chains in the urine is a marker of tubular dysfunction. In patients with impaired kidney function, serum concentrations and urinary excretion of polyclonal FLCs have been noted to be increased. Increased excretion of FLCs and other low-molecular weight proteins [cystatin C, NGAL] in the urine may contribute to progression of chronic kidney disease. Higher Cystatin C has been demonstrated to be related to development of albuminuria. Neutrophil gelatinase-associated lipcalin (NGAL) excretion in the urine is a marker of tubular injury in the kidney and has been shown to be elevated in subjects with type 1 and 2 diabetes mellitus (DM). Angiotensin-converting enzyme inhibitors (Ace Inh) and angiotensin II receptor blockers (ARB) class of drugs are renoprotective in nature and are the first line therapy for treatment of diabetic nephropathy. There is no longitudinal data evaluating the effect of Ace Inh and ARB class of drugs on urinary FLCs (UFLCs).

Our hypothesis is that UFLCs are increased in patients with DM with and without kidney disease and that treatment with Ace Inh and/or ARB will decrease UFLCs in these patients. Additionally, we will explore the change in other low molecular weight proteins [cystatin C, and NGAL] in response to treatment with Ace Inh and ARB.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University Health Sciences Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Type 2 Diabetes
  • Hypertension
  • Estimated glomerular filtration rate (eGFR) > 30 ml/min
  • Use of Ace Inh and ARB for control of blood pressure who are willing to be placed on alternate drug(s) in the washout period for blood pressure control

Exclusion Criteria:

  • Pregnancy
  • Patients with chronic kidney disease stage with eGFR < 30 ml/min (CKD stage IV and V)
  • Nephrotic range proteinuria (urinary protein > 3.5 gm/day)
  • History or renal transplantation
  • History of multiple myeloma
  • Known history of hypersensitivity reaction or intolerability to Ace Inh or ARB.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Washout Period for 30 days
In the washout period, the Ace Inh or ARB classes of medicine(s) that are part of the patient's antihypertensive regimen will be discontinued. The patient will be started on alternative therapy with medications that are approved by the Food and Drug Administration for treatment of high blood pressure (such as amlodipine, hydralazine, terazosin or Hydrochlorothiazide) for control of their blood pressure. The goal for their blood pressure will be set at < 140/90 mm/Hg. The washout period will last for four weeks at the end of which the patient will enter the test period.
Drug: amlodipine, hydralazine, terazosin or hydrochlorothiazide
In the washout period, the Ace Inh or ARB classes of medicine(s) that are part of the patient's antihypertensive regimen will be discontinued. The patient will be started on alternative therapy with medications that are approved by the Food and Drug Administration for treatment of high blood pressure (such as amlodipine, hydralazine, terazosin or Hydrochlorothiazide) for control of their blood pressure.
Other Names:
  • Norvasc

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Urine Microalbumin Creatinine Ratio
Time Frame: Visit 1 (Baseline), Visit 3 (Day 60)
Kidney function will be assessed throughout the study to assess changes in function prior to the washout of ACE/ARB medication and reintroduction of the ACE/ARB medication.
Visit 1 (Baseline), Visit 3 (Day 60)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the Level of Urinary Free Light Chains
Time Frame: Visit 1 (Baseline), Visit 3 (Day 60)
In relation to kidney function and washout/reintroduction of ACE/ARB medication the level of urinary free light chains will be assessed.
Visit 1 (Baseline), Visit 3 (Day 60)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tulane University School of Medicine

Investigators

  • Principal Investigator: Vechi Batuman, MD, Tulane University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2012

Primary Completion (Actual)

December 1, 2019

Study Completion (Actual)

December 1, 2019

Study Registration Dates

First Submitted

January 23, 2014

First Submitted That Met QC Criteria

January 23, 2014

First Posted (Estimated)

January 27, 2014

Study Record Updates

Last Update Posted (Actual)

August 21, 2023

Last Update Submitted That Met QC Criteria

August 17, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 258683

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hypertension

Clinical Trials on amlodipine, hydralazine, terazosin or hydrochlorothiazide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in United Arab Emirates

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe