The Effect of Renin Inhibition on Nerve Function in Diabetes

• Sponsor: Christiana Care Health Services (Other)
• Overall Status: Completed
• CT.gov ID: NCT00935064
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Arms: 2
• Duration (Months): 34
• Patients Per Site Per Month: 1.8

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Diabetes	Drug: Aliskiren; Other: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Renin Inhibition on Cardiovascular Autonomic Nerve Function in Diabetes
• Study Start Date: Jun 1, 2009
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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.
Placebo Comparator: Placebo	Other: Placebo; Placebo orally one tablet once a day for 6 weeks.

Outcome Measures

Primary Outcome Measures

1. Systolic Blood Pressure Before and After Treatment [baseline and 6 weeks]

   Systolic blood pressure at baseline and follow-up

2. Diastolic Blood Pressure Before and After Treatment [baseline and 6 weeks]

   Diastolic blood pressure at baseline and follow-up.

3. Serum Renin Level Before and After Treatment [baseline and 6 weeks]

   Serum renin level at baseline and follow-up

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Christiana Care Health Services	Newark	Delaware	United States	19713

Sponsors and Collaborators

• Christiana Care Health Services

Investigators

• Principal Investigator: Raelene E Maser, PhD, University of Delaware

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Christiana Care Health Services
• ClinicalTrials.gov Identifier: NCT00935064
• Other Study ID Numbers: 29011; NIH (INBRE 2-P20-RR016472-09)
• First Posted: Jul 8, 2009
• Last Update Posted: Aug 9, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Christiana Care Health Services: Diabetes
• Additional relevant MeSH terms: Diabetes Mellitus

Study Results

Participant Flow

Arm/Group Title	Aliskiren	Placebo
Arm/Group Description	300 mg, once daily, for 6 weeks	Once daily, for 6 weeks
Period Title: Overall Study
STARTED	30	30
COMPLETED	30	30
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Aliskiren	Placebo	Total
Arm/Group Description	300 mg, once daily, for 6 weeks	Once daily, for 6 weeks	Total of all reporting groups
Overall Participants	30	30	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	29 96.7%	26 86.7%	55 91.7%
>=65 years	1 3.3%	4 13.3%	5 8.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49 (12)	53 (12)	51 (12)
Sex: Female, Male (Count of Participants)
Female	16 53.3%	11 36.7%	27 45%
Male	14 46.7%	19 63.3%	33 55%
Region of Enrollment (participants) [Number]
United States	30 100%	30 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Systolic Blood Pressure Before and After Treatment
Description	Systolic blood pressure at baseline and follow-up
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aliskiren	Placebo
Arm/Group Description	300 mg, once daily, for 6 weeks	Once daily, for 6 weeks
Measure Participants	30	30
Baseline	121.0 (11.3)	124.1 (13.8)
Follow-up	112.1 (12.1)	121.5 (15.2)

2. Primary Outcome

Title	Diastolic Blood Pressure Before and After Treatment
Description	Diastolic blood pressure at baseline and follow-up.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aliskiren	Placebo
Arm/Group Description	300 mg, once daily, for 6 weeks	Once daily, for 6 weeks
Measure Participants	30	30
Baseline	66.1 (7.0)	68.2 (8.3)
Follow-up	61.5 (6.5)	66.7 (9.3)

3. Primary Outcome

Title	Serum Renin Level Before and After Treatment
Description	Serum renin level at baseline and follow-up
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aliskiren	Placebo
Arm/Group Description	300 mg, once daily, for 6 weeks	Once daily, for 6 weeks
Measure Participants	30	30
Baseline	2.4 (3.8)	3.1 (6.0)
Follow-up	0.5 (0.4)	2.6 (4.2)

4. Primary Outcome

Title	Mean Circular Resultant Before and After Treatment
Description	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.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aliskiren	Placebo
Arm/Group Description	300 mg, once daily, for 6 weeks	Once daily, for 6 weeks
Measure Participants	30	30
Baseline	41.8 (19.7)	38.2 (23.6)
Follow-up	50.8 (26.1)	37.5 (24.1)

5. Primary Outcome

Title	Expiration/Inspiration Ratio Before and After Treatment
Description	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.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aliskiren	Placebo
Arm/Group Description	300 mg, once daily, for 6 weeks	Once daily, for 6 weeks
Measure Participants	30	30
Baseline	1.22 (0.12)	1.21 (0.14)
Follow-up	1.28 (0.15)	1.20 (0.14)

Adverse Events

Arm/Group Title	Aliskiren		Placebo
Arm/Group Description	300 mg, once daily, for 6 weeks		Once daily, for 6 weeks
All Cause Mortality
	Aliskiren		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Aliskiren		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Aliskiren		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		3/30 (10%)
Metabolism and nutrition disorders
Hyperkalemia	1/30 (3.3%)	1	3/30 (10%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.