Clinical trial NCT00498433: Effects of Aliskiren and Amlodipine on the Renin-Angiotensin System (RAS) and Lipid/Carbohydrate Metabolism in Obese Patients With Hypertension
Official title: Part 1: An Open Label Pilot Study to Determine Interstitial and Tissue Concentrations of Aliskiren and Effects on the Renin- Angiotensin System (RAS) in Fat and Skeletal Muscle of Hypertensive Patients With Abdominal Obesity. Part 2: A Randomized, Double Blind, 12-weeks Parallel Group Study to Compare Effects of Aliskiren 300 mg and Amlodipine 5 mg on the RAS and Lipid/Carbohydrate Metabolism in Fat and Skeletal Muscle of Hypertensive Patients With Abdominal Obesity
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hypertension
Abdominal Obesity
Keywords: Aliskiren
Renin-Angiotensin System (RAS)
Hypertension
Abdominal obesity
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-07-10
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Part 1 determined: aliskiren, amlodipine and angiotensin II concentrations in interstitial fluid of fat and skeletal muscle; aliskiren and angiotensin II concentrations, and renin activity and concentration in fat and skeletal muscle tissues (biopsies); aliskiren, amlodipine and angiotensin II concentrations, and renin activity and concentration in plasma.

Part 2 investigated the potential for aliskiren to modulate renin-angiotensin-aldosterone system (RAAS) activity, and lipid/carbohydrate metabolism in adipose and skeletal muscle tissue in obese patients with hypertension in comparison to amlodipine.


Eligibility criteria: Inclusion criteria:

PART 1:

* Male and female patients 20 to 65 years of age with a diagnosis of hypertension and with abdominal obesity (waist circumference ≥ 102 cm in men and ≥ 88 cm in women)
* For patients with a history of treated hypertension, mean sitting systolic blood pressure (msSBP)/ mean sitting diastolic blood pressure (msDBP) had to be ≥ 120/80 mmHg and ≤ 160/100 mm Hg. For patients with newly diagnosed, untreated hypertension msSBP/msDBP had to be ≥ 135/85 mmHg and ≤ 160/100 mm Hg
* Pulse rate 40 - 90 bpm

PART 2:

* Male and female patients 18 to 65 years of age , with a diagnosis of hypertension and with abdominal obesity (waist circumference ≥ 102 cm in men and ≥ 88 cm in women)
* Systolic and diastolic blood pressure and pulse rate were assessed after the patient had rested for at least five (5) minutes. Vital signs had to be within the following ranges:

  1. Patients with history of treated hypertension: msSBP/msDBP ≥ 135/85 mmHg and \< 160/100 mmHg at baseline
  2. Patients with newly diagnosed, untreated hypertension: msSBP/msDBP ≥ 135/85 mmHg and \< 160/100 mmHg at screening and baseline.

Exclusion criteria:

PART 1

* Hypertension Grade 2 (msSBP ≥ 160 mmHg) or Grade 3 (msDBP ≥ 110 mmHg and/or msSBP ≥ 180 mmHg) WHO classification
* Current treatment with three or more antihypertensive drugs.

PART 2

* Hypertension Grade 2 (msSBP ≥ 160 and/or msDBP ≥ 100 mmHg).
* Current treatment with three or more antihypertensive drugs.

Other protocol-defined inclusion/exclusion criteria applied

Primary outcomes:
measure: Part 1: Aliskiren Concentrations From Interstitial Fluid (Microdialysis)at the End of Aliskiren Treatment Period
timeFrame: Day 42
measure: Part 1: Amlodipine Concentrations From Interstitial Fluid (Microdialysis) at the End of Amlodipine Treatment Period
timeFrame: Day 98
measure: Part 1: Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Aliskiren Treatment Period
timeFrame: Day 42
measure: Part 1: Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Amlodipine Treatment Period
timeFrame: Day 98
measure: Part 1: Aliskiren Concentrations From Tissue at the End of Aliskiren Treatment Period
timeFrame: Day 42
measure: Part 1: Angiotensin II Levels From Tissue During Aliskiren Treatment Period
timeFrame: Day 42
measure: Part 1: Renin Activity and Concentrations From Adipose and Skeletal Tissues During Aliskiren Treatment Period
timeFrame: Day 42
measure: Part 1: Aliskiren Concentrations From Plasma at the End of Aliskiren Treatment Period
timeFrame: Day 42
measure: Part 1: Amlodipine Concentrations From Plasma at the End of Amlodipine Treatment Period
timeFrame: Day 98
measure: Part 1: Angiotensin II Levels in Plasma During Aliskiren Treatment Period
timeFrame: Day 42
measure: Part 1: Angiotensin II Levels in Plasma During Amlodipine Treatment Period
timeFrame: Day 98
measure: Part 1: Renin Concentrations From Plasma During Aliskiren Treatment Period
timeFrame: Day 42
measure: Part 1: Renin Concentrations From Plasma During Amlodipine Treatment Period
timeFrame: Day 98
measure: Part 1: Renin Activity From Plasma During Aliskiren Treatment Period
timeFrame: Day 42
measure: Part 1: Renin Activity From Plasma During Amlodipine Treatment Period
timeFrame: Day 98
measure: Part 2: Change From Baseline in Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Double Blind Treatment Period
timeFrame: Placebo Baseline (Day 14), Active Treatment (Day 98)
measure: Part 2: Change From Baseline in Plasma Angiotensin II Levels During Double Blind Treatment Period
timeFrame: Placebo Baseline (Day 14), Active Treatment (Day 98)
measure: Part 2: Plasma Renin Activity (PRA) Concentration During Double Blind Treatment Period
timeFrame: Day 98
measure: Part 2: Plasma Renin Concentration (PRC) Levels During Double Blind Treatment Period
timeFrame: Day 98
Secondary outcomes:
measure: Part 2: Microdialysis Metabolic Analytes in Response to Insulin Modified Frequently Sampled Intravenous Glucose Test [IM-FSIGT]for Each Tissue (Adipose or Skeletal Muscle)
timeFrame: Day 14 and Day 98
measure: Part 2: Change From Baseline in Official Blood Pressure
timeFrame: Placebo Baseline (Day 14), Active Treatment (Day 98)
measure: Part 2: Renin Activity and Concentration of Aliskiren and Amlodipine in Fat and Skeletal Muscle Interstitial Fluid
timeFrame: Placebo Baseline (Day 14), Active Treatment (Day 98)
measure: 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)
timeFrame: Placebo Baseline (Day 14), Active Treatment (Day 98)
measure: Part 2: Change From Baseline in Mitochondrial Mass in Subcutaneous Fat and Skeletal Muscle (Tissue Biopsies)
timeFrame: Placebo Baseline (Day 14), Active Treatment (Day 98)
measure: Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death
timeFrame: 98 days
Other outcomes:
Locations:
city: Berlin-Buch
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Investigative site
name: Novartis
role: PRINCIPAL_INVESTIGATOR
References: