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

Diabetes Type 2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01165983
• Other study ID #: 2009P-000233
• Status: Completed
• Phase: N/A
• First received: December 15, 2009
• Last updated: January 26, 2015
• Start date: November 2009

Study information

• Verified date: January 2015
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. primary completion date: January 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 80 Years

Eligibility

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

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

5. 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

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

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

8. Any Other Serious Chronic Disease Requiring Active Treatment

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

10. Pregnancy

11. 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

12. 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

13. 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

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

5. 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

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

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

8. Any Other Serious Chronic Disease Requiring Active Treatment

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

10. Pregnancy

11. 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

12. 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

13. 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

14. Severe proliferative retinopathy that renders the subject legally blinded

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

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

17. 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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Diabetes Type 2

Intervention

Drug:
• Placebo
0mg tablet, taken orally for 12 weeks daily
• Aliskiren
150mg tablet, taken orally for 12 weeks daily

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center, Joslin Foot Center & Microcirculation Laboratory	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center	Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Flow Mediated Vasodilation	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.	Baseline	No
Primary	Flow Mediated Vasodilation	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.	12 Weeks post-randomization	No
Primary	Nitroglycerin Induced Dilation	Using ultrasound, images are taken pre- and post-vasodilation of the brachial artery induced with a 0.4mg tablet of NTG.	Baseline	No
Primary	Nitroglycerine Induced Vasodilation	Using ultrasound, images are taken pre- and post-vasodilation of the brachial artery induced with a 0.4mg tablet of NTG.	12 Weeks post-randomization	No
Primary	Skin Blood Flow Before and After Iontophoresis With Acetylcholine and Sodium Nitroprusside	Laser doppler imaging is used to measure microcirculatory changes pre- and post-iontophoresis of acetylcholine and sodium nitroprusside.	Baseline	No
Primary	Skin Blood Flow Before and After Iontophoresis With Acetylcholine and Sodium Nitroprusside	Laser doppler imaging is used to measure microcirculatory changes pre- and post-iontophoresis of acetylcholine (Ach) and sodium nitroprusside (NaNP).	12 Weeks post-randomization	No
Secondary	Absolute Change in Biochemical Markers of Endothelial Function, sICAM-1, ng/mL		12 Weeks post-randomization	No
Secondary	Absolute Change in Biochemical Markers of Endothelial Function, sVCAM-1, ng/mL		12 Weeks post-randomization	No
Secondary	Absolute Change in Biochemical Markers of Endothelial Function, t-PAI, pg/mL		12 Weeks post-randomization	No
Secondary	Absolute Change in Biochemical Markers of Endothelial Function, C-reactive Protein, µg/mL		12 Weeks post-randomization	No
Secondary	Absolute Change in Biochemical Markers of Endothelial Function, E-Selectin, ng/mL		12 Weeks post-randomization	No
Secondary	Absolute Change in Inflammatory Cytokines and Growth Factors, Osteoprotegerin, pg/mL		12 Weeks post-randomization	No
Secondary	Absolute Change in Inflammatory Cytokines and Growth Factors, Osteopontin, ng/mL		12 Weeks post-randomization	No
Secondary	Absolute Change in Inflammatory Cytokines and Growth Factors, G-CSF, pg/mL		12 Weeks post-randomization	No
Secondary	Absolute Change in Inflammatory Cytokines and Growth Factors, GM-CSF pg/mL		12 Weeks post-randomization	No
Secondary	Absolute Change in Inflammatory Cytokines and Growth Factors, IL-8, pg/mL		12 Weeks post-randomization	No
Secondary	Absolute Change in Inflammatory Cytokines and Growth Factors, MCP-1 pg/mL		12 Weeks post-randomization	No
Secondary	Absolute Change in Inflammatory Cytokines and Growth Factors, MDC ng/mL		12 Weeks post-randomization	No
Secondary	Absolute Change in Inflammatory Cytokines and Growth Factors, sCD-40L ng/mL		12 Weeks post-randomization	No
Secondary	Absolute Change in Inflammatory Cytokines and Growth Factors, TNFa, pg/mL		12 Weeks post-randomization	No