Clinical trial NCT00660309: A Clinical Study to Evaluate Renal Hemodynamic Responses to Aliskiren in Patients With Type 2 Diabetes Mellitus
Official title: An Open-label, Randomized, Parallel-group Study to Evaluate the Acute and Steady-state Renal Hemodynamic Responses to Aliskiren in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 diabetes mellitus
renal disease
hypertension
renal blood flow
retinal blood flow
aliskiren
irbesartan
captopril
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-04-17
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: The study objective was to assess the effect of single and multiple doses of aliskiren on renal plasma flow, glomerular filtration rate and to compare the effects of single and multiple doses of aliskiren versus captopril or irbesartan on renal blood flow, glomerular filtration rate, and retinal blood flow in patients with type 2 diabetes mellitus.


Eligibility criteria: Inclusion Criteria:

* Hypertensive, male and females of non-child bearing potential patients, with type 2 diabetes mellitus (T2DM) (diagnosed at least 8 weeks before Screening), with or without renal impairment; estimated glomerular filtration rate (eGFR) ≥ 40 mL/min/1.73 m\^2, documented at least 3 months before the study start, aged 18-75 years with a minimum body weight of 50 kg and having an appropriate intravenous access as determined by the study staff, able to communicate well were enrolled in the study.
* Patients must be on a stable dose of hypoglycemic medications for at least 8 weeks prior to the study.
* Patients must be medically able to discontinue anti- hypertensive medications for the duration of the study.

Exclusion Criteria:

* Patients with type 1 diabetes mellitus or uncontrolled T2DM (HbA1C\> 11%), eGFR \<40 mL/min/1.73 m\^2 (calculated by the Modification of Diet in Renal Disease (MDRD) formula), renal disease not caused by diabetes or hypertension, serum potassium \< 3.5 or \> 5.1 mEq/L, heart failure (New York Heart Association (NYHA) Class II-IV) or history of acute/decompensated heart failure within the 6 months prior to dosing, history of myocardial infarction, unstable angina pectoris, coronary bypass surgery, or any percutaneous coronary intervention (PCI) during the 6 months prior to the baseline visit, history of malignancy including leukemia and lymphoma within past five years, hypertensive encephalopathy any time in the past or cerebrovascular accident within the 6 months prior to the baseline visit, or with history of drug or alcohol abuse within the 12 months prior to dosing were excluded from the study.
* Patients with glaucoma, or prior ocular surgery.
* Patients with renal disease not caused by diabetes or hypertension.
* Patients with history of clinically significant drug or atopic allergy, acute or chronic respiratory disease, history of malignancy, or history of myocardial infarction, unstable angina pectoris, coronary bypass surgery, or any coronary intervention (percutaneous coronary intervention; PCI) during the 6 months prior to the study.
* Patients who had used any prescription drugs which may affect the renin-angiotensin-aldosterone system or with known effect on renal hemodynamics within 2 weeks prior to dosing and during the study, over-the-counter (OTC) medication within two (2) weeks prior to dosing,
* Any surgical or medical condition which may jeopardize the patient in case of participation in the study.
* Participation in any clinical investigation within 4 weeks prior to the study.
* Donation or loss of 400 mL or more of blood within 8 weeks prior to the study.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Aliskiren or Irbesartan
timeFrame: Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.
measure: Change From Baseline to Steady State Trough in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan
timeFrame: Day 2 and Day 15 at Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) .
measure: Change From Baseline to Steady State Peak in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan
timeFrame: Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and Day 15: 1, 2, 3, 4 and 5 hours post-dose.
measure: Change From Single Dose Peak to Steady State Peak in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan
timeFrame: Day 2 and Day 15: 1, 2, 3, 4 and 5 hours post-dose.
Secondary outcomes:
measure: Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Captopril
timeFrame: Day 1: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.
measure: Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Captopril
timeFrame: Day 1: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.
measure: Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Aliskiren or Irbesartan
timeFrame: Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.
measure: Change From Baseline to Steady State Trough in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan
timeFrame: Day 2 and Day 15 at Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) .
measure: Change From Baseline to Steady State Peak in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan
timeFrame: Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and Day 15: 1, 2, 3, 4 and 5 hours post-dose.
measure: Change From Single Dose Peak to Steady State Peak in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan
timeFrame: Day 2 and Day 15: 1, 2, 3, 4 and 5 hours post-dose.
measure: Change in Plasma Renin Concentration (PRC) After Captopril, Aliskiren or Irbesartan
timeFrame: Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.
measure: Change in Plasma Pro-renin Concentration After Captopril, Aliskiren or Irbesartan
timeFrame: Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.
measure: Change in Plasma Renin Activity (PRA) After Captopril, Aliskiren or Irbesartan
timeFrame: Predose and 5 hours post dose on Days 1, 2 and 15.
measure: Change in Plasma Angiotensin I After Captopril, Aliskiren or Irbesartan
timeFrame: Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.
measure: Change in Plasma Angiotensin II After Captopril, Aliskiren or Irbesartan
timeFrame: Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.
measure: Change in Serum Aldosterone After Captopril, Aliskiren or Irbesartan
timeFrame: Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.
measure: Change From Baseline in Retinal Blood Flow After Aliskiren or Irbesartan
timeFrame: Baseline (Day 1), Day 2 and Day 15.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Novartis Investigator Site
state: Massachusetts
Study officials:
affiliation: Novartis investigator site
name: Novartis
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hollenberg NK, Fisher ND, Nussberger J, Moukarbel GV, Barkoudah E, Danser AH. Renal responses to three types of renin-angiotensin system blockers in patients with diabetes mellitus on a high-salt diet: a need for higher doses in diabetic patients? J Hypertens. 2011 Dec;29(12):2454-61. doi: 10.1097/HJH.0b013e32834c627a.