The Effect of Renin Inhibition on Nerve Function in Diabetes

Effect of Renin Inhibition on Cardiovascular Autonomic Nerve Function in Diabetes

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00935064

Enrollment

Registered

2009-07-08

Start date

2009-06-30

Completion date

2012-04-30

Last updated

2016-08-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes

Keywords

Diabetes

Brief summary

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).

Interventions

DRUGAliskiren

Pill, 300 mg, once daily, for 6 weeks

OTHERPlacebo

Placebo orally one tablet once a day for 6 weeks.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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).

Design outcomes

Primary

Measure	Time frame	Description
Systolic Blood Pressure Before and After Treatment	baseline and 6 weeks	Systolic blood pressure at baseline and follow-up
Diastolic Blood Pressure Before and After Treatment	baseline and 6 weeks	Diastolic blood pressure at baseline and follow-up.
Serum Renin Level Before and After Treatment	baseline and 6 weeks	Serum renin level at baseline and follow-up
Mean Circular Resultant Before and After Treatment	baseline and 6 weeks	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.
Expiration/Inspiration Ratio Before and After Treatment	baseline and 6 weeks	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Aliskiren 300 mg, once daily, for 6 weeks	30
Placebo Once daily, for 6 weeks	30
Total	60

Baseline characteristics

Characteristic	Aliskiren	Placebo	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	1 Participants	4 Participants	5 Participants
Age, Categorical Between 18 and 65 years	29 Participants	26 Participants	55 Participants
Age, Continuous	49 years STANDARD_DEVIATION 12	53 years STANDARD_DEVIATION 12	51 years STANDARD_DEVIATION 12
Region of Enrollment United States	30 participants	30 participants	60 participants
Sex: Female, Male Female	16 Participants	11 Participants	27 Participants
Sex: Female, Male Male	14 Participants	19 Participants	33 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	1 / 30	3 / 30
serious Total, serious adverse events	0 / 30	0 / 30