Aliskiren Effect on Aortic Plaque Progression "ALPINE"

Terminated

Phase 2/3 Results

Update History

12 May '17
The Summary of Purpose was updated.
New
This study is being done to assess the effectiveness of short term (~9 months) Aliskiren/Placebo therapy to slow down the progression of atherosclerotic disease in thoracic and abdominal aorta. This will be checked by comparing before and after therapy magnetic resonance imaging (MRI) pictures of the aortic wall. Aliskiren is an FDA approved drug for hypertension but in this study is used for a new indication. Recent studies with animals have shown that Aliskiren therapy reduces the atherosclerotic plaque. Therefore, in this study, the investigators would like to evaluate whether the investigational drug Aliskiren, which is not FDA approved for this indication has the same beneficial effects in people with atherosclerotic disease.
Old
This study is being done to assess the effectiveness of short term (~9 months) Aliskiren/Placebo therapy to slow down the progression of atherosclerotic disease in thoracic and abdominal aorta. This will be checked by comparing before and after therapy magnetic resonance imaging (MRI) pictures of the aortic wall. Aliskiren is an FDA approved drug for hypertension but in this study is used for a new indication. Recent studies with animals have shown that Aliskiren therapy reduces the atherosclerotic plaque. Therefore, in this study, the investigators would like to evaluate whether the investigational drug Aliskiren, which is not FDA approved for this indication has the same beneficial effects in people with atherosclerotic disease.
The gender criteria for eligibility was updated to "All."
1 Jan '13
Trial name was updated.
New
Aliskiren Effect on Aortic Plaque Progression
The Summary of Purpose was updated.
New
This study is being done to assess the effectiveness of short term (~9 months) Aliskiren/Placebo therapy to slow down the progression of atherosclerotic disease in thoracic and abdominal aorta. This will be checked by comparing before and after therapy magnetic resonance imaging (MRI) pictures of the aortic wall. Aliskiren is an FDA approved drug for hypertension but in this study is used for a new indication. Recent studies with animals have shown that Aliskiren therapy reduces the atherosclerotic plaque. Therefore, in this study, the investigators would like to evaluate whether the investigational drug Aliskiren, which is not FDA approved for this indication has the same beneficial effects in people with atherosclerotic disease.
Old
This study is being done to assess the effectiveness of short term (~9 months) Aliskiren/Placebo therapy to slow down the progression of atherosclerotic disease (hardening of the arteries) in thoracic aorta (this is a large vessel coming out of your heart). This will be checked by comparing before and after therapy magnetic resonance imaging (MRI) pictures of your aortic wall. Aliskiren is an FDA approved drug for hypertension but in this study is used for a new indication. Recent studies with animals have shown that Alikiren therapy reduces the atherosclerotic plaque. Therefore, in this study, the investigators would like to evaluate whether the investigational drug Aliskiren, which is not FDA approved for this indication has the same beneficial effects in people with atherosclerotic disease.
The description was updated.
New
Treatments and Clinic Visits: The 36-week double-blind, randomized treatment phase of the trial is preceded by 2-week single-blind placebo period to assess eligibility into the active treatment period, compliance, and to confirm the baseline blood pressure values of the enrolled subjects. If at the end of the single-blind phase, inclusion criteria will not be met, the participants will not be allowed to continue on to the trial. If they are eligible they will undergo baseline MRI studies after being randomized to either placebo or Aliskiren 150 mg, with an escalation to 300 mg at 2 weeks into treatment. This dose will be maintained for the duration of the trial. After randomization and dose escalation visits (at 2 weeks), patients will return for scheduled clinic visits at weeks 12 and 36. Assessment of routine safety measures including serum creatinine and potassium will be performed at pre-designated visits (randomization, drug escalation and end-of trial). At each study visit, after having the patient in a sitting position for 5 minutes, SBP/diastolic blood pressure will be measured 3 times in accordance with the AHA Committee Report on blood pressure determination. The patient will be then asked to stand for 2 minutes, and a single blood pressure measurement will be measured in the standing position. Evidence of left ventricular hypertrophy (LVH) will be determined using the Romhilt-Estes scoring system at baseline. Specialized measurements of plasma including insulin, glucose measures, adipokines (leptin and adiponectin) and high- sensitivity C-reactive protein (hsCRP) will be performed at randomization and 12 weeks into the trial. Central aortic blood pressure assessment will be performed at randomization and end of trial/exit visits (SphygmoCor CP, AtCor Medical, Itaska, Illinois, USA). Plasma direct renin measurements will be obtained at baseline and 12 weeks in part to assess compliance of patients with their therapy (Diasource, Belgium).
Old
None.
The eligibility criteria were updated.
New
Inclusion Criteria: Patients, both males and females, were eligible if they were ≥ 45 years of age, with previously documented cardiovascular disease, defined as at least one of the following: myocardial infarction (MI), cerebrovascular accident (CVA), coronary bypass surgery and/or percutaneous intervention, peripheral arterial disease (PAD), defined as ankle brachial index (ABI) <0.9 and/or prior peripheral intervention/surgery. Subjects on angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blockers (ARB) therapy were eligible to participate, provided no dose adjustments were made during the course of the study. Exclusion Criteria: Contraindications to the MRI exam (pacemakers, metallic implants, severe claustrophobia); diagnosis of Type II Diabetes or use of hypoglycemic drugs; uncontrolled hypertension (>145/90 mm Hg); low density lipoprotein (LDL) of ≥ 130mg/dL; renal insufficiency defined as glomerular filtration rate (GFR) ≤ 40 ml/minute (derived by the Modified Diet in Renal Disease (MDRD) equation); initiation of new therapy with statins, ACEI/ARBs, anti-oxidants, calcium channel blockers, diuretics, β blockers; transient ischemic cerebral attack during the prior 6 months; history of allergy to renin inhibitors; unstable cardiac syndromes; symptomatic arrhythmias; history of malignancy including leukemia and lymphoma (but not basal cell skin cancer, cured squamous cell cancer and localized prostate cancer) and history of allergy to renin inhibitors.
Old
Inclusion Criteria: - Subjects 45 years and older. - Male or female subjects are eligible. Female subjects must be either post-menopausal for one year, surgically sterile, or using effective contraceptive forms such as barrier method with spermicide or an intra-uterine device. Oral contraceptive use is disallowed. - Subjects with established heart or vascular disease defined as: - Subjects with previous documented MI or CVA AND/OR - Subjects with PAD (defined as prior evidence of abnormal ABI (<0.9) and/or prior peripheral intervention/surgery) - Subjects with bypass surgery and/or stent placement treatment - LDL cholesterol <130 mg/dL. - Blood pressures >145/90 mm Hg at visit 2 - Subjects who are eligible and able to participate in the study who consent to do so after the purpose and nature of the investigation has been clearly explained to them (written informed consent). - Subjects who agree to be available for every clinic visit. All study visits will occur in the morning. - Subjects on ACE and or ARB therapy will be allowed in the trial provided no dose adjustments are made during the course of the study. Exclusion Criteria: - Uncontrolled hypertension defined as SBP>150mm Hg and/or DBP>95 mmHg at visit 1 and SBP > 145 mm Hg in visit 2. - Creatinine >1.5. - Initiation of new therapy with statins, ACE/ARB, anti-oxidants, calcium channel blockers, diuretics, β blockers. - Contraindications to MRI (pacemakers, metallic implants, severe claustrophobia). - Transient ischemic cerebral attack during the last 6 months. - Evidence of a secondary form of hypertension, such as coarctation of the aorta, hyperaldosteronism, unilateral renal disease, or pheochromocytoma. - Dyslipidemia secondary to other causes. This includes, but is not restricted to alcoholism, auto-immune disease, nephrotic syndrome, any viral or non viral hepatitis clinically active within 12 months prior to study entry, obstructive hepatic or biliary disease, dys- or macroglobulinemia, multiple myeloma, glycogen storage disease, uncontrolled hypothyroidism or hyperthyroidism, insulin dependent or non insulin-dependent diabetes mellitus, chronic pancreatitis and porphyria. - Insulin dependent or non-insulin dependent diabetes mellitus (diabetic subjects may be enrolled if controlled only with diet). - Known contraindication, including history of allergy to renin inhibitors. - Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by the evidence of any of the following: - History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection. - Current active or recurrent irritable bowel syndrome (IBS) or history of inflammatory bowel syndrome. Subjects with a past history of IBS without symptoms for at least 6 months prior to the study start, will be allowed to enter the trial. - Current active gastritis, ulcers or gastrointestinal or rectal bleeding. - Subjects that are on any renal replacement therapy ( hemodialysis, peritoneal dialysis, hemofiltration, renal transplantation) - Impaired renal function is indicated by serum creatinine levels greater than 1.5 x ULN at Visit 1. If creatinine is between 1.5 and 2 x ULN, one retest will be allowed provided all other criteria are fulfilled. Serum creatinine levels must be < 1.5 x ULN at the retest for the subject to be eligible for further study participation. If serum creatinine is greater than 2 x ULN at any timepoint between Week-2 and 0, the subject will be excluded from further study participation. - Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia. - Sodium depletion. - History of malignancy including leukemia and lymphoma (but not basal cell skin cancer, cured squamous cell cancer and localized Prostate cancer). - History of any severe, life-threatening disease. - Any surgical or medical conditions which, at the discretion of the investigator, place the subject at higher risk derived from his/her participation into the study, or are likely to prevent the subject from complying with the requirements of the study or completing the trial period. - History of drug abuse within the last 2 years. - History of noncompliance to medical regimens, or those subjects unwilling to comply with the study protocol. - Participation in any investigational drug trial within one month prior to Visit 1. - Unwillingness or inability to give informed consent. - Persons directly involved in the execution of this protocol.
A location was updated in Columbus.
New
The overall status was removed for Ohio State University.
6 Oct '11
The eligibility criteria were updated.
New
Inclusion Criteria: - Subjects 45 years and older. - Male or female subjects are eligible. Female subjects must be either post-menopausal for one year, surgically sterile, or using effective contraceptive forms such as barrier method with spermicide or an intra-uterine device. Oral contraceptive use is disallowed. - Subjects with established heart or vascular disease defined as: - Subjects with previous documented MI or CVA AND/OR - Subjects with PAD (defined as prior evidence of abnormal ABI (<0.9) and/or prior peripheral intervention/surgery) - Subjects with bypass surgery and/or stent placement treatment - LDL cholesterol <130 mg/dL. - Blood pressures >145/90 mm Hg at visit 2 - Subjects who are eligible and able to participate in the study who consent to do so after the purpose and nature of the investigation has been clearly explained to them (written informed consent). - Subjects who agree to be available for every clinic visit. All study visits will occur in the morning. - Subjects on ACE and or ARB therapy will be allowed in the trial provided no dose adjustments are made during the course of the study. Exclusion Criteria: - Uncontrolled hypertension defined as SBP>150mm Hg and/or DBP>95 mmHg at visit 1 and SBP > 145 mm Hg in visit 2. - Creatinine >1.5. - Initiation of new therapy with statins, ACE/ARB, anti-oxidants, calcium channel blockers, diuretics, β blockers. - Contraindications to MRI (pacemakers, metallic implants, severe claustrophobia). - Transient ischemic cerebral attack during the last 6 months. - Evidence of a secondary form of hypertension, such as coarctation of the aorta, hyperaldosteronism, unilateral renal disease, or pheochromocytoma. - Dyslipidemia secondary to other causes. This includes, but is not restricted to alcoholism, auto-immune disease, nephrotic syndrome, any viral or non viral hepatitis clinically active within 12 months prior to study entry, obstructive hepatic or biliary disease, dys- or macroglobulinemia, multiple myeloma, glycogen storage disease, uncontrolled hypothyroidism or hyperthyroidism, insulin dependent or non insulin-dependent diabetes mellitus, chronic pancreatitis and porphyria. - Insulin dependent or non-insulin dependent diabetes mellitus (diabetic subjects may be enrolled if controlled only with diet). - Known contraindication, including history of allergy to renin inhibitors. - Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by the evidence of any of the following: - History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection. - Current active or recurrent irritable bowel syndrome (IBS) or history of inflammatory bowel syndrome. Subjects with a past history of IBS without symptoms for at least 6 months prior to the study start, will be allowed to enter the trial. - Current active gastritis, ulcers or gastrointestinal or rectal bleeding. - Subjects that are on any renal replacement therapy ( hemodialysis, peritoneal dialysis, hemofiltration, renal transplantation) - Impaired renal function is indicated by serum creatinine levels greater than 1.5 x ULN at Visit 1. If creatinine is between 1.5 and 2 x ULN, one retest will be allowed provided all other criteria are fulfilled. Serum creatinine levels must be < 1.5 x ULN at the retest for the subject to be eligible for further study participation. If serum creatinine is greater than 2 x ULN at any timepoint between Week-2 and 0, the subject will be excluded from further study participation. - Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia. - Sodium depletion. - History of malignancy including leukemia and lymphoma (but not basal cell skin cancer, cured squamous cell cancer and localized Prostate cancer). - History of any severe, life-threatening disease. - Any surgical or medical conditions which, at the discretion of the investigator, place the subject at higher risk derived from his/her participation into the study, or are likely to prevent the subject from complying with the requirements of the study or completing the trial period. - History of drug abuse within the last 2 years. - History of noncompliance to medical regimens, or those subjects unwilling to comply with the study protocol. - Participation in any investigational drug trial within one month prior to Visit 1. - Unwillingness or inability to give informed consent. - Persons directly involved in the execution of this protocol.
Old
Inclusion Criteria: - Subjects 45 years and older. - Male or female subjects are eligible. Female subjects must be either post-menopausal for one year, surgically sterile, or using effective contraceptive forms such as barrier method with spermicide or an intra-uterine device. Oral contraceptive use is disallowed. - Subjects with established heart or vascular disease defined as: - Subjects with previous documented MI or CVA AND/OR - Subjects with PAD (defined as prior evidence of abnormal ABI (<0.9) and/or prior peripheral intervention/surgery) - Subjects with bypass surgery and/or stent placement treatment - LDL cholesterol <130 mg/dL. - Blood pressures >145/90 mm Hg at visit 2 - Subjects who are eligible and able to participate in the study who consent to do so after the purpose and nature of the investigation has been clearly explained to them (written informed consent). - Subjects who agree to be available for every clinic visit. All study visits will occur in the morning. - Subjects on ACE and or ARB therapy will be allowed in the trial provided no dose adjustments are made during the course of the study. Exclusion Criteria: - Uncontrolled hypertension defined as SBP>150mm Hg and/or DBP>95 mmHg at visit 1 and SBP > 145 mm Hg in visit 2. - Creatinine >1.5. - Initiation of new therapy with statins, ACE/ARB, anti-oxidants, calcium channel blockers, diuretics, ? blockers. - Contraindications to MRI (pacemakers, metallic implants, severe claustrophobia). - Transient ischemic cerebral attack during the last 6 months. - Evidence of a secondary form of hypertension, such as coarctation of the aorta, hyperaldosteronism, unilateral renal disease, or pheochromocytoma. - Dyslipidemia secondary to other causes. This includes, but is not restricted to alcoholism, auto-immune disease, nephrotic syndrome, any viral or non viral hepatitis clinically active within 12 months prior to study entry, obstructive hepatic or biliary disease, dys- or macroglobulinemia, multiple myeloma, glycogen storage disease, uncontrolled hypothyroidism or hyperthyroidism, insulin dependent or non insulin-dependent diabetes mellitus, chronic pancreatitis and porphyria. - Insulin dependent or non-insulin dependent diabetes mellitus (diabetic subjects may be enrolled if controlled only with diet). - Known contraindication, including history of allergy to renin inhibitors. - Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by the evidence of any of the following: - History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection. - Current active or recurrent irritable bowel syndrome (IBS) or history of inflammatory bowel syndrome. Subjects with a past history of IBS without symptoms for at least 6 months prior to the study start, will be allowed to enter the trial. - Current active gastritis, ulcers or gastrointestinal or rectal bleeding. - Subjects that are on any renal replacement therapy ( hemodialysis, peritoneal dialysis, hemofiltration, renal transplantation) - Impaired renal function is indicated by serum creatinine levels greater than 1.5 x ULN at Visit 1. If creatinine is between 1.5 and 2 x ULN, one retest will be allowed provided all other criteria are fulfilled. Serum creatinine levels must be < 1.5 x ULN at the retest for the subject to be eligible for further study participation. If serum creatinine is greater than 2 x ULN at any timepoint between Week-2 and 0, the subject will be excluded from further study participation. - Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia. - Sodium depletion. - History of malignancy including leukemia and lymphoma (but not basal cell skin cancer, cured squamous cell cancer and localized Prostate cancer). - History of any severe, life-threatening disease. - Any surgical or medical conditions which, at the discretion of the investigator, place the subject at higher risk derived from his/her participation into the study, or are likely to prevent the subject from complying with the requirements of the study or completing the trial period. - History of drug abuse within the last 2 years. - History of noncompliance to medical regimens, or those subjects unwilling to comply with the study protocol. - Participation in any investigational drug trial within one month prior to Visit 1. - Unwillingness or inability to give informed consent. - Persons directly involved in the execution of this protocol.