Effects of Aliskiren and Amlodipine on the Renin-Angiotensin System (RAS) and Lipid/Carbohydrate Metabolism in Obese Patients With Hypertension

Browse trials for

• Hypertension 6,834
• Obesity, Abdominal 283

Keywords

• Aliskiren
• Renin-Angiotensin System (RAS)
• Hypertension
• Abdominal obesity

Hypertension

6,834 studies on the registry are indexed under Hypertension; 971 are open to participants now.

This study's enrollment of 46 is below the median of 90 across 5,095 interventional studies indexed under Hypertension.

Lead sponsor

Novartis is the lead sponsor of 714 studies on the registry; none are open to participants now.

Study arms

• Experimental
  Aliskiren

  Part 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase (period 1) consisting of treatment with one tablet of placebo to aliskiren once daily (o.d.). This was followed by a 4 week treatment phase (period 2) consisting of treatment with 300 mg aliskiren o.d.. Part 2: Eligible randomized patients in this arm received aliskiren 300 mg tablet o.d. and amlodipine placebo capsule o.d. for 12 weeks.

  Drug: Aliskiren · Drug: Placebo of Aliskiren · Drug: Placebo of amlodipine

• Active comparator
  Amlodipine

  Part 1: After aliskiren treatment (period 2), each patient was entered into a second washout period (4 weeks) during which blood pressure was required to be ≤ 140/90 mmHg. If blood pressure exceeded 140/90 mmHg on two consecutive days (home monitoring) and was confirmed at the study center, the patient was entered into the amlodipine treatment period (period 3). In period 3, all patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks. Part 2: Eligible patients randomized to part 2 received amlodipine 5 mg o.d. and aliskiren placebo for 12 weeks

  Drug: Amlodipine · Drug: Placebo of Aliskiren

Interventions

• DrugAliskiren

  300 mg tablet once daily

  Also known as: SPP100

• DrugAmlodipine

  5 mg capsule once daily

• DrugPlacebo of Aliskiren

  Matching placebo of aliskiren 300 mg tablet

• DrugPlacebo of amlodipine

  Matching placebo of amlodipine 5 mg capsule

Primary outcomes

1. Part 1: Aliskiren Concentrations From Interstitial Fluid (Microdialysis)at the End of Aliskiren Treatment Period

   Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method. Interstitial fluid was collected for measurements of drug concentrations on the last day of the aliskiren treatment periods (Day 42).

   Time frame: Day 42

2. Part 1: Amlodipine Concentrations From Interstitial Fluid (Microdialysis) at the End of Amlodipine Treatment Period

   Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method. Interstitial fluid was collected for measurements of drug concentration on the last day of the amlodipine treatment periods (Day 98).

   Time frame: Day 98

3. Part 1: Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Aliskiren Treatment Period

   Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.

   Time frame: Day 42

4. Part 1: Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Amlodipine Treatment Period

   Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.

   Time frame: Day 98

5. Part 1: Aliskiren Concentrations From Tissue at the End of Aliskiren Treatment Period

   Biopsies were taken from abdominal adipose and skeletal muscle tissue to determine aliskiren concentration. Tissue biopsy samples for drug concentrations analyses were taken on the last day of the aliskiren treatment periods (Day 42).

   Time frame: Day 42

6. Part 1: Angiotensin II Levels From Tissue During Aliskiren Treatment Period

   Biopsies were taken from abdominal adipose and skeletal muscle tissue to determine Ang II concentration.

   Time frame: Day 42

7. Part 1: Renin Activity and Concentrations From Adipose and Skeletal Tissues During Aliskiren Treatment Period

   Time frame: Day 42

8. Part 1: Aliskiren Concentrations From Plasma at the End of Aliskiren Treatment Period

   Plasma samples were obtained for measurement of aliskiren or amlodipine concentrations. All blood samples were taken by an indwelling cannula inserted in a forearm vein or direct venipuncture. The plasma samples for drug concentrations analyses were taken on the last day of the aliskiren treatment periods (Day 42).

   Time frame: Day 42

9. Part 1: Amlodipine Concentrations From Plasma at the End of Amlodipine Treatment Period

   Plasma samples were obtained for measurement of aliskiren or amlodipine concentrations. All blood samples were taken by an indwelling cannula inserted in a forearm vein or direct venipuncture. The plasma samples for drug concentrations analyses were taken on the last day of the amlodipine treatment periods (Day 98).

   Time frame: Day 98

10. Part 1: Angiotensin II Levels in Plasma During Aliskiren Treatment Period

    Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.

    Time frame: Day 42

11. Part 1: Angiotensin II Levels in Plasma During Amlodipine Treatment Period

    Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.

    Time frame: Day 98

12. Part 1: Renin Concentrations From Plasma During Aliskiren Treatment Period

    Renin concentrations from plasma were measured as: plasma renin concentration (PRC), prorenin concentration and total renin concentration (renin + prorenin concentration).

    Time frame: Day 42

13. Part 1: Renin Concentrations From Plasma During Amlodipine Treatment Period

    Renin concentrations from plasma were measured as plasma renin concentration (PRC), prorenin concentration and total renin concentration (renin + prorenin concentration).

    Time frame: Day 98

14. Part 1: Renin Activity From Plasma During Aliskiren Treatment Period

    Plasma Renin activity (PRC) was measured by a trapping PRA (tPRA) assay.

    Time frame: Day 42

15. Part 1: Renin Activity From Plasma During Amlodipine Treatment Period

    Plasma renin activity (PRC) was measured by a trapping PRA (tPRA) assay.

    Time frame: Day 98

16. Part 2: Change From Baseline in Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Double Blind Treatment Period

    Interstitial fluid was obtained from subcutaneous adipose and skeletal muscle tissues by microdialysis using the zero-flow method to determine Ang II concentration.

    Time frame: Placebo Baseline (Day 14), Active Treatment (Day 98)

17. Part 2: Change From Baseline in Plasma Angiotensin II Levels During Double Blind Treatment Period

    Plasma Ang II was measured prior to and 1 hour after the Insulin modified-frequently sampled intravenous glucose tolerance test (IM-FSIGT) during placebo treatment (Days 14) and active treatment(Day 98).

    Time frame: Placebo Baseline (Day 14), Active Treatment (Day 98)

18. Part 2: Plasma Renin Activity (PRA) Concentration During Double Blind Treatment Period

    Time frame: Day 98

19. Part 2: Plasma Renin Concentration (PRC) Levels During Double Blind Treatment Period

    Time frame: Day 98

Secondary outcomes

1. Part 2: Microdialysis Metabolic Analytes in Response to Insulin Modified Frequently Sampled Intravenous Glucose Test [IM-FSIGT]for Each Tissue (Adipose or Skeletal Muscle)

   Time frame: Day 14 and Day 98

2. Part 2: Change From Baseline in Official Blood Pressure

   Time frame: Placebo Baseline (Day 14), Active Treatment (Day 98)

3. Part 2: Renin Activity and Concentration of Aliskiren and Amlodipine in Fat and Skeletal Muscle Interstitial Fluid

   Time frame: Placebo Baseline (Day 14), Active Treatment (Day 98)

4. Part 2: Change From Baseline in Peripheral Insulin Sensitivity in Response to Insulin Modified Frequently Sampled Intravenous Glucose Test [IM-FSIGT]for Each Tissue (Adipose or Skeletal Muscle)

   Time frame: Placebo Baseline (Day 14), Active Treatment (Day 98)

5. Part 2: Change From Baseline in Mitochondrial Mass in Subcutaneous Fat and Skeletal Muscle (Tissue Biopsies)

   Time frame: Placebo Baseline (Day 14), Active Treatment (Day 98)

6. Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death

   Time frame: 98 days

Baseline characteristics