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

This study is currently recruiting participants.
Verified December 2013 by University of Virginia
Sponsor:
Information provided by (Responsible Party):
Kambiz Kalantarinia, University of Virginia
ClinicalTrials.gov Identifier:
NCT01101269
First received: April 6, 2010
Last updated: December 17, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention
Type 2 Diabetes
Drug: ACEI or ARB
Drug: Lisinopril

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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).

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Change in renal blood flow (RBF) [ Time Frame: Study day 10 ] [ Designated as safety issue: No ]
    We will use Contrast Enhanced Ultrasound using Definity as the contrast agent to monitor changes in renal blood flow (RBF).

  • Change in renal blood flow (RBF) [ Time Frame: Compared to Study Day 17 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Proteinuria [ Time Frame: Study day 10 ] [ Designated as safety issue: No ]
  • Change in Proteinuria [ Time Frame: Compared to study day 17 ] [ Designated as safety issue: No ]

Estimated Enrollment: 54
Study Start Date: February 2010
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01101269

Contacts
Contact: Kambiz Kalanarinia, MD 434-924-5125 kk6c@virginia.edu

Locations
United States, Virginia
University of Virginia Health System Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Kambiz Kalantarinia, MD    434-924-5125    kk6c@virginia.edu   
Contact: Lisa F Johnson, BA, CCRC    434-982-3198    sfj8n@virginia.edu   
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Kambiz Kalantarinia, MD University of Virginia
  More Information

No publications provided

Responsible Party: Kambiz Kalantarinia, MD, University of Virginia
ClinicalTrials.gov Identifier: NCT01101269     History of Changes
Other Study ID Numbers: 14815
Study First Received: April 6, 2010
Last Updated: December 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Virginia:
Diabetic nephropathy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Kidney Diseases
Proteinuria
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Urination Disorders
Urological Manifestations
Signs and Symptoms
Angiotensin-Converting Enzyme Inhibitors
Lisinopril
Enzyme Inhibitors
Angiotensin Receptor Antagonists
Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 16, 2014