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NCT Number: NCT02046395

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

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.

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Key information

Conditions

Type 2 Diabetes Cardiovascular Diseases Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Hypertension Metabolic Diseases Nutritional and Metabolic Diseases Vascular Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

amlodipine, hydralazine, terazosin or hydrochlorothiazide

Drug

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

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

Sponsors and collaborators

Lead sponsor

Tulane University School of Medicine

Other

Registry information

Acronym: UFLC

Important dates

Study start
2012
Primary completion
2019
Study completion
2019
First posted
Jan 27, 2014
Registry last updated
Aug 21, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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