The Effect of Aliskiren on Endothelial Function in Pre-Diabetes and Diabetes

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01165983
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 124
• Location: 1
• Arms: 2

Study Details

Study Description

Brief Summary

The purpose of this research is to study and determine the effects of Aliskiren on blood vessels and blood flow. The primary hypothesis is that Aliskiren will increase endothelial function by 30% or more in comparison to the placebo group.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Type 2	Drug: Placebo; Drug: Aliskiren	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 124 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: The Effect of Aliskiren on Endothelial Function in Pre-Diabetes and Diabetes
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; 0mg tablet, taken orally for 12 weeks daily
Experimental: Aliskiren	Drug: Aliskiren; 150mg tablet, taken orally for 12 weeks daily; Other Names: Trade name: Tekturna

Outcome Measures

Primary Outcome Measures

1. Flow Mediated Vasodilation [Baseline]

   Using ultrasound, percent change in brachial artery diameter is measured in response to an increase in shear stress from a tightened blood pressure cuff, which causes endothelium-dependent dilatation.

2. Flow Mediated Vasodilation [12 Weeks post-randomization]

   Using ultrasound, percent change in brachial artery diameter is measured in response to an increase in shear stress from a tightened blood pressure cuff, which causes endothelium-dependent dilatation.

3. Nitroglycerin Induced Dilation [Baseline]

   Using ultrasound, images are taken pre- and post-vasodilation of the brachial artery induced with a 0.4mg tablet of NTG.

4. Nitroglycerine Induced Vasodilation [12 Weeks post-randomization]

   Using ultrasound, images are taken pre- and post-vasodilation of the brachial artery induced with a 0.4mg tablet of NTG.

5. Skin Blood Flow Before and After Iontophoresis With Acetylcholine and Sodium Nitroprusside [Baseline]

   Laser doppler imaging is used to measure microcirculatory changes pre- and post-iontophoresis of acetylcholine and sodium nitroprusside.

6. Skin Blood Flow Before and After Iontophoresis With Acetylcholine and Sodium Nitroprusside [12 Weeks post-randomization]

   Laser doppler imaging is used to measure microcirculatory changes pre- and post-iontophoresis of acetylcholine (Ach) and sodium nitroprusside (NaNP).

Secondary Outcome Measures

1. Absolute Change in Biochemical Markers of Endothelial Function, sICAM-1, ng/mL [12 Weeks post-randomization]

2. Absolute Change in Biochemical Markers of Endothelial Function, sVCAM-1, ng/mL [12 Weeks post-randomization]

3. Absolute Change in Biochemical Markers of Endothelial Function, t-PAI, pg/mL [12 Weeks post-randomization]

4. Absolute Change in Biochemical Markers of Endothelial Function, C-reactive Protein, μg/mL [12 Weeks post-randomization]

5. Absolute Change in Biochemical Markers of Endothelial Function, E-Selectin, ng/mL [12 Weeks post-randomization]

6. Absolute Change in Inflammatory Cytokines and Growth Factors, Osteoprotegerin, pg/mL [12 Weeks post-randomization]

7. Absolute Change in Inflammatory Cytokines and Growth Factors, Osteopontin, ng/mL [12 Weeks post-randomization]

8. Absolute Change in Inflammatory Cytokines and Growth Factors, G-CSF, pg/mL [12 Weeks post-randomization]

9. Absolute Change in Inflammatory Cytokines and Growth Factors, GM-CSF pg/mL [12 Weeks post-randomization]

10. Absolute Change in Inflammatory Cytokines and Growth Factors, IL-8, pg/mL [12 Weeks post-randomization]

11. Absolute Change in Inflammatory Cytokines and Growth Factors, MCP-1 pg/mL [12 Weeks post-randomization]

12. Absolute Change in Inflammatory Cytokines and Growth Factors, MDC ng/mL [12 Weeks post-randomization]

13. Absolute Change in Inflammatory Cytokines and Growth Factors, sCD-40L ng/mL [12 Weeks post-randomization]

14. Absolute Change in Inflammatory Cytokines and Growth Factors, TNFα, pg/mL [12 Weeks post-randomization]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Group 1. Subjects At Risk of Developing Type 2 Diabetes

INCLUSION CRITERIA

1. Ages of 21-80 years

2. Subjects "at risk" of developing type 2 Diabetes Mellitus (First degree relatives history of type 2 Diabetes Mellitus, History of gestational Diabetes, Known impaired glucose tolerance, Impaired fasting plasma glucose 100-126 mg/dl at the time of enrollment)

EXCLUSION CRITERIA

1. Treatment with Aliskiren (Tekturna)

2. Smokers (use of tobacco products in the previous 3 months)

3. Active or Uncontrolled Cardiovascular Disease

• Myocardial infarction, or angina within 12 months of study participation

• Arrhythmia (uncontrolled, highly symptomatic, requiring treatment or life-threatening)

• CHF (Class III and IV symptoms of heart failure on less than ordinary exertion or at rest)

• Stroke or Transient Ischemic Attack (TIA) within 12 months of study participation

• Uncontrolled Hypertension (SBP >180 mmHg or DBP >105 mmHg; 2 abnormal readings during visit)

• History of previous hypotensive episodes

1. Liver Disease (AST, ALT, Alk Phos levels > 2x UNL)

2. Renal Disease (creatinine > 1.7 mg/dL for women and >2.0 mg/dL for men and/or estimated GFR <30 mL/min, history of dialysis, nephrotic syndrome and known renovascular hypertension) at the time of enrollment

3. Hyperkalemia (serum potassium >5.0 meq/L)

4. Severe Dyslipidemia (TG > 600 mg/dL or Cholesterol >350 mg/dL)

5. Any Other Serious Chronic Disease Requiring Active Treatment

6. Females of Childbearing Potential Not Using an Effective Form of Birth Control as Determined by co-investigators

7. Pregnancy

8. Taking Any of the Following Medications:

• Systemic (not inhaled) Glucocorticoids

• Antineoplastic Agents

• Cyclosporine, Ketoconazole, Furosemide, Warfarin

• Bronchodilators (aminophyline, inhaled beta agonists) on a regular basis

1. Patient is known to have a history of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) and/or positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result in the past

2. History of drug or alcohol abuse within the 12months prior to dosing or evidence of such abuse as indicated by laboratory assays conducted during screening or baseline evaluations

Group 2. Type 2 Diabetic Patients

INCLUSION CRITERIA

1. Ages of 21-80 years

2. Type 2 Diabetes Mellitus stable and not expected to change during the study period

EXCLUSION CRITERIA

1. Treatment with Aliskiren (Tekturna)

2. Smokers (use of tobacco products in the previous 3 months)

3. Active or Uncontrolled Cardiovascular Disease

• Myocardial infarction, or angina within 12 months of study participation

• Arrhythmia (uncontrolled, highly symptomatic, requiring treatment or life-threatening)

• CHF (Class III and IV symptoms of heart failure on less than ordinary exertion or at rest)

• Stroke or Transient Ischemic Attack (TIA) within 12 months of study participation

• Uncontrolled Hypertension (SBP >180 mmHg or DBP >105 mmHg; 2 abnormal readings during visit)

• History of previous hypotensive episodes

1. Liver Disease (AST, ALT, Alk Phos levels > 2x UNL)

2. Renal Disease (creatinine > 1.7 mg/dL for women and >2.0 mg/dL for men and/or estimated GFR <30 mL/min, history of dialysis, nephrotic syndrome and known renovascular hypertension) at the time of enrollment

3. Hyperkalemia (serum potassium >5.0 meq/L)

4. Severe Dyslipidemia (TG > 600 mg/dL or Cholesterol >350 mg/dL)

5. Any Other Serious Chronic Disease Requiring Active Treatment

6. Females of Childbearing Potential Not Using an Effective Form of Birth Control as Determined by co-investigators

7. Pregnancy

8. Taking Any of the Following Medications:

• Systemic (not inhaled) Glucocorticoids

• Antineoplastic Agents

• Cyclosporine, Ketoconazole, Furosemide, Warfarin

• Bronchodilators (aminophyline, inhaled beta agonists) on a regular basis

1. Patient is known to have a history of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) and/or positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result in the past

2. History of drug or alcohol abuse within the 12months prior to dosing or evidence of such abuse as indicated by laboratory assays conducted during screening or baseline evaluations

3. Severe proliferative retinopathy that renders the subject legally blinded

4. Previous diagnosis of severe gastroparesis diabeticorum due to autonomic neuropathy that has necessitated hospital admission

5. Presence of non-healing foot ulceration due to severe peripheral diabetic neuropathy

6. Documented diabetic nephropathy manifested as macro-albuminuria, (2 of 3 urine specimens collected within a 3-6 month period with urine albumin>300 ug/mg creatinine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center, Joslin Foot Center & Microcirculation Laboratory	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Aristidis Veves, MD, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Aristidis Veves, Rongxiang Xu, MD Professor of Surgery in the Field of Regenerative Therapeutics, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT01165983
• Other Study ID Numbers: 2009P000233
• First Posted: Jul 20, 2010
• Last Update Posted: Mar 28, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Prediabetic State; Diabetes Mellitus, Type 2

Study Results

Participant Flow

Pre-assignment Detail	A total of 124 subjects signed the ICF, but after screening procedures, 24 were found ineligible so only 100 were randomized to placebo or Aliskiren.

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Period Title: Overall Study
STARTED	51	49
COMPLETED	46	42
NOT COMPLETED	5	7

Baseline Characteristics

Arm/Group Title	Placebo	Aliskiren	Total
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily	Total of all reporting groups
Overall Participants	51	49	100
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54 (11)	54 (11)	54 (11)
Sex: Female, Male (Count of Participants)
Female	20 39.2%	30 61.2%	50 50%
Male	31 60.8%	19 38.8%	50 50%
Region of Enrollment (participants) [Number]
United States	51 100%	49 100%	100 100%

Outcome Measures

1. Primary Outcome

Title	Flow Mediated Vasodilation
Description	Using ultrasound, percent change in brachial artery diameter is measured in response to an increase in shear stress from a tightened blood pressure cuff, which causes endothelium-dependent dilatation.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects at Risk of DMII	T2DM Patients
Arm/Group Description
Measure Participants	48	52
Mean (Standard Deviation) [percentage change over baseline]	4.8 (0.7)	4.4 (2.6)

2. Primary Outcome

Title	Flow Mediated Vasodilation
Description	Using ultrasound, percent change in brachial artery diameter is measured in response to an increase in shear stress from a tightened blood pressure cuff, which causes endothelium-dependent dilatation.
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

Number of subjects that completed the study

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	0.3	0.8
Diabetic Patients, Placebo n=25, Aliskiren n=22	0.4	0.9

3. Primary Outcome

Title	Nitroglycerin Induced Dilation
Description	Using ultrasound, images are taken pre- and post-vasodilation of the brachial artery induced with a 0.4mg tablet of NTG.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects at Risk of DMII	T2DM Patients
Arm/Group Description
Measure Participants	48	52
Mean (Standard Deviation) [percent change]	16.5 (4.8)	15.2 (5.0)

4. Primary Outcome

Title	Nitroglycerine Induced Vasodilation
Description	Using ultrasound, images are taken pre- and post-vasodilation of the brachial artery induced with a 0.4mg tablet of NTG.
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	0.4	-0.8
Diabetic Patients, Placebo n=25, Aliskiren n=22	-1.4	-0.3

5. Primary Outcome

Title	Skin Blood Flow Before and After Iontophoresis With Acetylcholine and Sodium Nitroprusside
Description	Laser doppler imaging is used to measure microcirculatory changes pre- and post-iontophoresis of acetylcholine and sodium nitroprusside.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects at Risk of DMII	T2DM Patients
Arm/Group Description
Measure Participants	48	52
Acetylcholine induced skin vasodilation	45	38
Sodium nitroprusside skin induced vasodilation	38	36

6. Primary Outcome

Title	Skin Blood Flow Before and After Iontophoresis With Acetylcholine and Sodium Nitroprusside
Description	Laser doppler imaging is used to measure microcirculatory changes pre- and post-iontophoresis of acetylcholine (Ach) and sodium nitroprusside (NaNP).
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Ach, Placebo n=21, Aliskiren n=20	6	-1
At risk of T2DM, NaNP, Placebo n=21 Aliskiren n=20	-1	13
Diabetic Patient, Ach, Placebo n=25 Aliskiren n=22	-5	3
Diabetic Patient, NaNP, Placebo n=25 Ali. n=22	-9	8

7. Secondary Outcome

Title	Absolute Change in Biochemical Markers of Endothelial Function, sICAM-1, ng/mL
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	21	30
Diabetic Patients, Placebo n=25, Aliskiren n=22	13	14

8. Secondary Outcome

Title	Absolute Change in Biochemical Markers of Endothelial Function, sVCAM-1, ng/mL
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	335	236
Diabetic Patients, Placebo n=25, Aliskiren n=22	185	106

9. Secondary Outcome

Title	Absolute Change in Biochemical Markers of Endothelial Function, t-PAI, pg/mL
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	45	30
Diabetic Patients, Placebo n=25, Aliskiren n=22	54	26

10. Secondary Outcome

Title	Absolute Change in Biochemical Markers of Endothelial Function, C-reactive Protein, μg/mL
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	-1.0	-0.6
Diabetic Patients, Placebo n=25, Aliskiren n=22	-1.7	-2.0

11. Secondary Outcome

Title	Absolute Change in Biochemical Markers of Endothelial Function, E-Selectin, ng/mL
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	1.9	0.7
Diabetic Patients, Placebo n=25, Aliskiren n=22	0.6	-0.7

12. Secondary Outcome

Title	Absolute Change in Inflammatory Cytokines and Growth Factors, Osteoprotegerin, pg/mL
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	-36	97
Diabetic Patients, Placebo n=25, Aliskiren n=22	-24	48

13. Secondary Outcome

Title	Absolute Change in Inflammatory Cytokines and Growth Factors, Osteopontin, ng/mL
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	-0.3	2.2
Diabetic Patients, Placebo n=25, Aliskiren n=22	1.7	0.2

14. Secondary Outcome

Title	Absolute Change in Inflammatory Cytokines and Growth Factors, G-CSF, pg/mL
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	1.1	4.0
Diabetic Patients, Placebo n=25, Aliskiren n=22	1.9	4.4

15. Secondary Outcome

Title	Absolute Change in Inflammatory Cytokines and Growth Factors, GM-CSF pg/mL
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	0.4	-0.8
Diabetic Patients, Placebo n=25, Aliskiren n=22	-1.6	0.4

16. Secondary Outcome

Title	Absolute Change in Inflammatory Cytokines and Growth Factors, IL-8, pg/mL
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	-2.2	-2.0
Diabetic Patients, Placebo n=25, Aliskiren n=22	-2.4	0.6

17. Secondary Outcome

Title	Absolute Change in Inflammatory Cytokines and Growth Factors, MCP-1 pg/mL
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	-11	-7
Diabetic Patients, Placebo n=25, Aliskiren n=22	36	8

18. Secondary Outcome

Title	Absolute Change in Inflammatory Cytokines and Growth Factors, MDC ng/mL
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	-0.09	-0.07
Diabetic Patients, Placebo n=25, Aliskiren n=22	-0.07	0.04

19. Secondary Outcome

Title	Absolute Change in Inflammatory Cytokines and Growth Factors, sCD-40L ng/mL
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	-0.8	-3.2
Diabetic Patients, Placebo n=25, Aliskiren n=22	3.3	-3.6

20. Secondary Outcome

Title	Absolute Change in Inflammatory Cytokines and Growth Factors, TNFα, pg/mL
Time Frame	12 Weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily	Aliskiren: 150mg tablet, taken orally for 12 weeks daily
Measure Participants	46	42
At risk of T2DM, Placebo n=21, Aliskiren n=20	-0.15	-0.21
Diabetic Patients, Placebo n=25, Aliskiren n=22	0.30	-0.09

Adverse Events

Adverse Event Reporting Description	Number for "at risk" of Diabetic Ketoacidosis reduced to reflect number of subjects enrolled who were diagnosed with T2DM. Diabetic ketoacidosis is primarily a concern in patients with T1DM, however the patient who experienced ketoacidosis was later shown to have undiagnosed T1DM, improperly diagnosed as T2DM.
Arm/Group Title	Placebo		Aliskiren
Arm/Group Description	Placebo: 0mg tablet, taken orally for 12 weeks daily		Aliskiren: 150mg tablet, taken orally for 12 weeks daily
All Cause Mortality
	Placebo		Aliskiren
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Aliskiren
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/46 (0%)		4/42 (9.5%)
Cardiac disorders
Cardiac event	0/46 (0%)		2/42 (4.8%)
Endocrine disorders
Diabetic Ketoacidosis	0/27 (0%)		1/21 (4.8%)
Skin and subcutaneous tissue disorders
Cellulitis	0/46 (0%)		1/42 (2.4%)
Other (Not Including Serious) Adverse Events
	Placebo		Aliskiren
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/46 (13%)		7/42 (16.7%)
Blood and lymphatic system disorders
Decreased hematocrit	1/46 (2.2%)		0/42 (0%)
Increase in eosinophil levels	0/46 (0%)		1/42 (2.4%)
Ear and labyrinth disorders
Tinnitus	0/46 (0%)		1/42 (2.4%)
Endocrine disorders
Decrease in Blood Glucose	1/46 (2.2%)		0/42 (0%)
Gastrointestinal disorders
Constipation	1/46 (2.2%)		0/42 (0%)
GI virus	1/46 (2.2%)		0/42 (0%)
Bloating and gas	0/46 (0%)		1/42 (2.4%)
General disorders
Mild increase in Serum Calcium Level	2/46 (4.3%)		1/42 (2.4%)
Increase in serum creatinine levels	0/46 (0%)		1/42 (2.4%)
Decrease in serum calcium	0/46 (0%)		1/42 (2.4%)
Musculoskeletal and connective tissue disorders
Numbness and cramping	1/46 (2.2%)		1/42 (2.4%)
Renal and urinary disorders
Increased urination	0/46 (0%)		1/42 (2.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.