Nebivolol Versus Sustained Release Metoprolol Succinate in Patients With Chronic Kidney Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of Michigan
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Rajiv Saran, University of Michigan
ClinicalTrials.gov Identifier:
NCT01291888
First received: February 8, 2011
Last updated: January 7, 2013
Last verified: January 2013
  Purpose

The investigators postulate that nebivolol will be more effective than an equivalent dose of a comparative BB, specifically sustained release metoprolol succinate, in improving the availability of NO, lowering blood pressure, and reducing albuminuria with implications for slowing progression of CKD and cardiovascular protection in this high risk population.

The objective of this proposal is to conduct a randomized pilot clinical trial to determine the relative efficacy and tolerability of nebivolol versus sustained release metoprolol succinate in improving blood pressure in patients with CKD and albuminuria. The primary endpoint would be a decrease in asymmetric dimethyl arginine (ADMA). Secondary endpoints would include a reduction in blood pressure, urinary F2-isoprostanes and albuminuria.


Condition
Chronic Kidney Disease

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Efficacy and Tolerability of Nebivolol Versus Sustained Release Metoprolol Succinate in Patients With Chronic Kidney Disease: A Single-center Randomized Trial.

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Primary Efficacy [ Time Frame: Baseline to End of Study ] [ Designated as safety issue: No ]
    The primary efficacy variable will be the change in ADMA level from baseline to end of study.


Secondary Outcome Measures:
  • Secondary Efficacy [ Time Frame: Baseline to End of Study ] [ Designated as safety issue: No ]
    Secondary efficacy parameters will include: the change in blood pressure, GFR, urinary albumin excretion, and biomarkers including urinary F2-Isoprostanes, BNP, hsCRP, Cystatin C, and a measure of insulin resistance-the homeostatic model assessment (HOMA) from baseline to end of study


Biospecimen Retention:   Samples Without DNA

A total of 30 ml blood (CBC with differential and platelets-3ml, comprehensive panel-5-7ml, biomarkers-20ml) will be drawn by venipuncture typically from the antecubital vein at baseline visit (30ml), and week 6-study midpoint (30ml) and end of study (30ml). At the screening visit only 10ml blood will be required (CBC and Comprehensive Panel).


Estimated Enrollment: 50
Study Start Date: March 2011
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

A total of 50 patients with CKD meeting the inclusion and exclusion criteria listed below will after informed consent be randomized to either nebivolol or sustained release metoprolol succinate and followed for 3 months or early termination of the study.

Criteria

Inclusion Criteria:

  • Age > 18 years old and < 85 years old
  • Willing and able to comply with all study procedures
  • Blood pressure on standard antihypertensive therapy, which may include: a diuretic, ACE-I, ARB, CCB, and/or an alpha adrenergic antagonist, and a blood pressure ≤ 180 mm Hg systolic and ≥ 130 mm Hg systolic. The blood pressure will be taken after a period of 15 minutes of resting in the sitting posture
  • Clinically stable patients with CKD (GFR 20-60 ml/min/1.73 m²) by the abbreviated MDRD equation and with a rate of decline of GFR no greater than 1 ml/min/1.73 m² per month over the prior three months and with albuminuria (urine albumin:creatinine ratio) in a spot urine sample of between 100-3000 mcg/g of creatinine). Albumin excretion (i.e., urine albumin:creatinine ratio) will be checked prior to enrollment in two separate (collected at least one week apart) spot early morning urine specimens
  • Females of child bearing potential must have a negative pregnancy test at screening. Females considered not of childbearing potential include those who have been in menopause at least 2 years, had tubal ligation at least 1 year prior to screening or who have had a total hysterectomy

Exclusion Criteria:

  • Use of a BB in the 3 months prior to study enrollment, other than atenolol or metoprolol
  • Uncontrolled hypertension with a blood pressure > 160/100 mm Hg or those with changes to their antihypertensive regime during the last 2 months
  • Concurrent disease or conditions that would interfere with study participation or safety, such as bleeding disorders, history of syncope or vertigo, severe gastrointestinal reflux (GERD) or gastric ulcers, heart failure, symptomatic coronary or peripheral vascular disease, arrhythmia, serious neurological disorders including seizures or organ transplantation
  • Diabetics that are uncontrolled (HbA1c consistently > 9.0 g/dL), unstable, newly diagnosed, or have undergone major changes in therapy within the last 2 months
  • Any severe co-morbid condition that would limit life expectancy to < 6 months
  • Advanced CKD with an eGFR < 20 ml/min/1.73 m²
  • Patients with albuminuria due to causes other than diabetes mellitus or hypertension
  • Hepatic enzyme concentrations > 2 times the upper limit of normal
  • HIV infection, hepatic cirrhosis or other preexisting liver disease; or positive HIV, Hepatitis B or C test at screening
  • Use of any investigational product or investigational medical device within the last 60 days of screening
  • History of alcohol and or drug abuse
  • Any condition that in view of the investigators places the subject at high risk of poor treatment or compliance or of not completing the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01291888

Contacts
Contact: Rajiv Saran, MBBS MD MS MRCP 734-7631521 rsaran@umich.edu
Contact: Manilay K Pulsinelli, BS 734-763-4268 keomany@umich.edu

Locations
United States, Michigan
University of Michigan Health Systems Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Rajiv Saran, MD, MS, MRCP    734-763-1521    rsaran@umich.edu   
Contact: Manilay K Pulsinelli, BS    734-763-4268    keomany@umich.edu   
Sponsors and Collaborators
University of Michigan
Forest Laboratories
Investigators
Principal Investigator: Rajiv Saran, MD, MS, MRCP University of Michigan
  More Information

No publications provided

Responsible Party: Rajiv Saran, MBBS, MD, MS, MRCP, University of Michigan
ClinicalTrials.gov Identifier: NCT01291888     History of Changes
Other Study ID Numbers: HUM00034784
Study First Received: February 8, 2011
Last Updated: January 7, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Urologic Diseases
Metoprolol
Metoprolol succinate
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Autonomic Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sympatholytics
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014