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

Beth Israel Lahey Health

Status: Completed

Conditions: Diabetes Type 2

Treatments: Drug: Placebo; Drug: Aliskiren

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01165983

2009P000233

Details and patient eligibility

About

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.

Enrollment: 124 patients

Sex: All

Ages: 21 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

124 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

Aliskiren

Experimental group

Treatment:

Drug: Aliskiren