Effect of Angiotensin Converting Enzyme Inhibitor, Lisinopril, on Renal Blood Flow and Its Correlation With Proteinuria Reduction in Subjects With Type 2 Diabetes and Kidney Disease

Effect of Angiotensin Converting Enzyme Inhibitor, Lisinopril, on Renal Blood Flow and Its Correlation With Proteinuria Reduction in Subjects With Type 2 Diabetes and Kidney Disease (KXK005).

The purpose of the study is to investigate the effect of a blood pressure medication, Lisinopril, or similar drugs in that class, on the flow of blood to the kidneys. In this study, we will compare blood flow to the kidneys in healthy people that do not have diabetes or kidney disease with people that have diabetes and evidence of kidney disease.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: ACEI or ARB; Drug: Lisinopril

Detailed Description

Blockers of renin angiotensin aldosterone system (RAAS) are considered the standard of care in treatment of diabetic nephropathy. Their effects are thought to be through multiple mechanisms, including reducing intraglomerular pressure. However, due to the lack of a sensitive, practical and noninvasive method of monitoring renal hemodynamics, the magnitude of hemodynamic effects of these agents and its contribution to proteinuria reduction has not been studied in humans. At the same time, it is not clear if treatment with blockers of the RAAS have similar renal hemodynamic effects in individuals with and without diabetes and kidney disease.

Up to 36 subjects with type 2 diabetes and more than 150 mg of proteinuria who are on stable doses of ACE inhibitors or angiotensin receptor blockers (ARBs) and up to 18 healthy volunteers will be enrolled in this study. Subjects with type 2 diabetes will be asked to stop their ACE inhibitor or ARB medications for 10 days. Between 7 to 10 days after stopping these medications renal blood flow (RBF) will be measured using contrast enhanced ultrasound (CEU) and urine protein will be measured as well for comparison to baseline. Subjects' ACE inhibitors or ARB will be restarted and RBF measurement using CEU and measurement of urine protein excretion will be repeated after 7 days. For comparison, RBF will be measured by CEU in up to 18 healthy volunteers. They will then be started on Lisinopril 10 mg orally once a day for 7 days. On day 7 RBF measurement will be repeated to assess the effect of ACE inhibitors on RBF in healthy individuals as compared to those with diabetic nephropathy.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion For subjects with diabetic nephropathy,

1. Adults (ages 40 - 75 years)
2. Diagnosis of type 2 diabetes for more than 5 years

3. Evidence of diabetic nephropathy as evidenced by

   a. More than 150 mg of proteinuria per day in a 24-hour urine collection, or a spot morning urine protein to creatinine of greater than 0.15, or a spot morning urine albumin to creatinine ratio greater than 100 confirmed on two separate occasions within 12 months

4. Treatment with a blocker of the renin -angiotensin-aldosterone system (either ACE inhibitor or ARB)

For healthy controls,

1. Adults (ages 40 - 75 years)
2. Good general health

Exclusion For subjects with diabetic nephropathy,

1. Type 1 diabetes
2. Glomerular filtration rate less than 40 ml/min/1.73 m2 by MDRD formula
3. Hemoglobin A1C greater than 10%
4. Blood pressure greater than 150/90 mm Hg or less than 100/55 mm Hg
5. History of kidney transplantation
6. Oxygen saturation is less than 80%
7. History of unstable cardiopulmonary conditions, known intracardiac shunts, or pulmonary hypertension
8. History of active cancer within the last 3 years

For healthy controls,

1. History or clinical evidence of any chronic disease
2. Chronic and regular use of any medications except for oral contraceptives and vitamins
3. Clinically significant abnormal screening laboratory values
4. Pregnancy or lactation for women
5. Blood pressure at screening visit less than 110/60
6. History of unstable cardiopulmonary conditions, known intracardiac shunts, or pulmonary hypertension
7. History of active cancer within the last 3 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Subjects with diabetic nephropathy; Renal blood flow (RBF) will be measured using contrast enhanced ultrasound (CEU) and urine protein will be measured both on and off angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB).	Drug: ACEI or ARB; Subjects will be asked to discontinue their usual ACE inhibitor or Angiotensin Receptor Blocker (ARB) for ten days, undergo a CEU using Definity (for renal blood flow assessment) as the contrast agent, then resume their usual ACEI or ARB for ten days, then undergo another CEU using Definity as the contrast agent.
ACTIVE_COMPARATOR: Healthy volunteers; Renal blood flow (RBF) will be measured using contrast enhanced ultrasound (CEU) and urine protein will be measured both on and off angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB).	Drug: Lisinopril; Subjects will be undergo a CEU using Definity (for renal blood flow assessment) as the contrast agent, then take Lisinopril 10 mg every day for 7 days, after which they will undergo another CEU using Definity as the contrast agent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in renal blood flow (RBF)	We will use Contrast Enhanced Ultrasound using Definity as the contrast agent to monitor changes in renal blood flow (RBF).	Study day 10
Change in renal blood flow (RBF)		Compared to Study Day 17

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Proteinuria	Study day 10
Change in Proteinuria	Compared to study day 17

Collaborators and Investigators

• Sponsor: University of Virginia

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: April 6, 2010
• First Submitted That Met QC Criteria: April 8, 2010
• First Posted (ESTIMATE): April 9, 2010

Study Record Updates

• Last Update Posted (ACTUAL): May 12, 2017
• Last Update Submitted That Met QC Criteria: May 10, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Diabetic nephropathy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Urological Manifestations; Endocrine System Diseases; Urination Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Proteinuria; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Protective Agents; Cardiotonic Agents; Angiotensin-Converting Enzyme Inhibitors; Lisinopril
• Other Study ID Numbers: 14815