Clinical trial NCT01165983: The Effect of Aliskiren on Endothelial Function in Pre-Diabetes and Diabetes
Official title: The Effect of Aliskiren on Endothelial Function in Pre-Diabetes and Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Type 2
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2010-07-20
Enrollment: 124
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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

Primary outcomes:
measure: Flow Mediated Vasodilation
timeFrame: Baseline
measure: Flow Mediated Vasodilation
timeFrame: 12 Weeks post-randomization
measure: Nitroglycerin Induced Dilation
timeFrame: Baseline
measure: Nitroglycerine Induced Vasodilation
timeFrame: 12 Weeks post-randomization
measure: Skin Blood Flow Before and After Iontophoresis With Acetylcholine and Sodium Nitroprusside
timeFrame: Baseline
measure: Skin Blood Flow Before and After Iontophoresis With Acetylcholine and Sodium Nitroprusside
timeFrame: 12 Weeks post-randomization
Secondary outcomes:
measure: Absolute Change in Biochemical Markers of Endothelial Function, sICAM-1, ng/mL
timeFrame: 12 Weeks post-randomization
measure: Absolute Change in Biochemical Markers of Endothelial Function, sVCAM-1, ng/mL
timeFrame: 12 Weeks post-randomization
measure: Absolute Change in Biochemical Markers of Endothelial Function, t-PAI, pg/mL
timeFrame: 12 Weeks post-randomization
measure: Absolute Change in Biochemical Markers of Endothelial Function, C-reactive Protein, μg/mL
timeFrame: 12 Weeks post-randomization
measure: Absolute Change in Biochemical Markers of Endothelial Function, E-Selectin, ng/mL
timeFrame: 12 Weeks post-randomization
measure: Absolute Change in Inflammatory Cytokines and Growth Factors, Osteoprotegerin, pg/mL
timeFrame: 12 Weeks post-randomization
measure: Absolute Change in Inflammatory Cytokines and Growth Factors, Osteopontin, ng/mL
timeFrame: 12 Weeks post-randomization
measure: Absolute Change in Inflammatory Cytokines and Growth Factors, G-CSF, pg/mL
timeFrame: 12 Weeks post-randomization
measure: Absolute Change in Inflammatory Cytokines and Growth Factors, GM-CSF pg/mL
timeFrame: 12 Weeks post-randomization
measure: Absolute Change in Inflammatory Cytokines and Growth Factors, IL-8, pg/mL
timeFrame: 12 Weeks post-randomization
measure: Absolute Change in Inflammatory Cytokines and Growth Factors, MCP-1 pg/mL
timeFrame: 12 Weeks post-randomization
measure: Absolute Change in Inflammatory Cytokines and Growth Factors, MDC ng/mL
timeFrame: 12 Weeks post-randomization
measure: Absolute Change in Inflammatory Cytokines and Growth Factors, sCD-40L ng/mL
timeFrame: 12 Weeks post-randomization
measure: Absolute Change in Inflammatory Cytokines and Growth Factors, TNFα, pg/mL
timeFrame: 12 Weeks post-randomization
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center, Joslin Foot Center & Microcirculation Laboratory
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Aristidis Veves, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dushay JR, Tecilazich F, Kafanas A, Magargee ML, Auster ME, Gnardellis C, Dinh T, Veves A. Aliskiren improves vascular smooth muscle function in the skin microcirculation of type 2 diabetic patients with normal renal function. J Renin Angiotensin Aldosterone Syst. 2015 Jun;16(2):344-52. doi: 10.1177/1470320313489060. Epub 2013 May 13.