The Effect of Renin Inhibition on Nerve Function in Diabetes

Effect of Renin Inhibition on Cardiovascular Autonomic Nerve Function in Diabetes

This study will assess the effect of direct renin inhibition on nerve function in persons with diabetes using a double-blind, placebo-controlled randomized trial involving two treatment arms (i.e., [1] 30 participants enrolled and randomized to 300 mg of Aliskiren; [2] 30 participants enrolled and randomized to placebo).

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Drug: Aliskiren; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care Health Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Individuals >18 years old with type 1 or type 2 diabetes mellitus.

Exclusion Criteria:

• Individuals currently taking the maximum dose of an ACE inhibitor or an ARB.
• Individuals with a history of a MI, percutaneous coronary interventions, coronary artery bypass graft (CABG) surgery, acute coronary syndromes, recent/on going atrial fibrillation, frequent atrial arrhythmias, frequent ventricular arrhythmias, or acute myocardial ischemia changes.
• Individuals whose treatment dosage changes 2 months prior to the study for antihypertensive and antidiabetes medications, and the following medications that may affect the ANS: anti-tuberculosis drugs, nitrofurantoin, metronidazole, chloramphenicol, perhexiline maleate, amiodarone, clofibrate, tricyclic antidepressants, phenytoin, barbiturates, neuroleptic, antiparkinsonism drugs, and nitrated drugs.
• Pregnant or lactating females.
• Individuals with impaired renal function (i.e., creatinine >1.5 mg/dl), a history of dialysis, nephritic syndrome or renovascular hypertension.
• Individuals with potassium levels within 0.5 mmol/L of the upper limit of normal (i.e., hyperkalemia).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo orally one tablet once a day for 6 weeks.
Active Comparator: Aliskiren; Pill, 300 mg, once daily, for 6 weeks	Drug: Aliskiren; Pill, 300 mg, once daily, for 6 weeks; Other: Placebo; Placebo orally one tablet once a day for 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic Blood Pressure Before and After Treatment	Systolic blood pressure at baseline and follow-up	baseline and 6 weeks
Diastolic Blood Pressure Before and After Treatment	Diastolic blood pressure at baseline and follow-up.	baseline and 6 weeks
Serum Renin Level Before and After Treatment	Serum renin level at baseline and follow-up	baseline and 6 weeks
Mean Circular Resultant Before and After Treatment	Mean circular resultant at baseline and follow-up. There are several different assessment modalities used for the determination of cardiovascular autonomic function (i.e. HRV). One widely used clinical method for assessing HRV is RR-variation during deep breathing. RR-variation is a measure of the change in heart rate resulting from the variation in intrathoracic pressure due to respiration. It is predominantly a function of parasympathetic activity. In this study, RR-variation during deep breathing, performed for 6 min, was measured by vector analysis [i.e. mean circular resultant (MCR)] and by the expiration/inspiration (E/I) ratio of the first six breath cycles. With regard to the MCR, the length of the vector mean is proportional to the degree of HRV. Weinberg and Pfeifer first introduced the assessment of HRV via determination of the MCR in a paper in Biometrics 1984:40:855-861. Low HRV is considered to be less favorable.	baseline and 6 weeks
Expiration/Inspiration Ratio Before and After Treatment	Expiration/inspiration ratio at baseline and follow-up. There are several different assessment modalities used for the determination of cardiovascular autonomic function (i.e. HRV). One widely used clinical method for assessing HRV is RR-variation during deep breathing. RR-variation is a measure of the change in heart rate resulting from the variation in intrathoracic pressure due to respiration. It is predominantly a function of parasympathetic activity. In this study, RR-variation during deep breathing, performed for 6 min, was measured by vector analysis [i.e. mean circular resultant (MCR)] and by the expiration/inspiration (E/I) ratio of the first six breath cycles.	baseline and 6 weeks

Collaborators and Investigators

• Sponsor: Christiana Care Health Services
• Investigators: Principal Investigator: Raelene E Maser, PhD, University of Delaware

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: July 7, 2009
• First Submitted That Met QC Criteria: July 7, 2009
• First Posted (Estimate): July 8, 2009

Study Record Updates

• Last Update Posted (Estimate): August 9, 2016
• Last Update Submitted That Met QC Criteria: July 7, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus
• Other Study ID Numbers: 29011; NIH (INBRE 2-P20-RR016472-09)