The Effect of Tekturna on Endothelial Function and Endothelial Progenitor Cells in Patients With Early Atherosclerosis

NCT01067326 | Terminated Phase 3 Results

• 3 other identifiers: 09-007617R01AG031750R01HL092954
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

We will study the hypothesis that long-term Tekturna treatment will improve endothelial function and the production and function of endothelial progenitor cells (EPCs) in patients with early atherosclerosis. Specifically, long-term Tekturna treatment will increase the Reactive Hyperemia Peripheral Arterial Tonometry indexes and increase the numbers and the function of circulating endothelial progenitor cells, compared to placebo, in association with a reduction in inflammation and oxidative stress.

Conditions

Endothelial Dysfunction

Keywords

Endothelial Dysfunction; Endothelial Function; Tekturna; Endothelial Peripheral Arterial Tomography (EndoPAT); Progenitor Cells; renin inhibition; endothelial progenitor cells; early atherosclerosis

Outcome Measures

Primary Outcomes (2)

• Endothelial Progenitor Cells (EPC)

  Peripheral blood mononuclear cells were stained for EPC markers (cell-surface antigens CD34/CD133/KDR) and counted by flow-cytometry.

  Baseline, 4 Months

• Reactive Hyperemia Index (RHI)

  RHI was measured by the noninvasive endothelial peripheral arterial tomography (EndoPat) test. EndoPAT results are reported as the "Endoscore" (range 0-3); a score of 1.67 and lower indicates the need for immediate medical attention; a score between 1.68 and 2 indicates a need to reduce risk factors; a score above 2.1 indicates a healthy heart.

  Baseline, 4 Months

Secondary Outcomes (2)

• Systolic Blood Pressure

  Baseline, 4 Months

• Diastolic Blood Pressure

  Baseline, 4 Months

Study Arms (2)

Aliskiren

ACTIVE COMPARATOR

150 mg Aliskiren once daily for a period of 4 months.

Drug: Aliskiren

Placebo

PLACEBO COMPARATOR

1 pill per day by mouth for 4 months.

Drug: Placebo

Interventions

Aliskiren DRUG

150 mg Aliskiren once daily for a period of 4 months

Also known as: Tekturna, Rasilez

Aliskiren

Placebo DRUG

1 pill per day by mouth for 4 months

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years old
• More than two of the following cardiovascular risk factors (determined by prescreen phone call): family history of cardiovascular disease, physical inactivity/sedentary lifestyle, obesity or overweight, family history of diabetes mellitus or hypertension, total cholesterol \> 200 mg/dL, LDL \> 130 mg/dL, HDL \< 50 mg/dL, smoking, stress, or Triglycerides \> 150 mg/dL
• Demonstrated endothelial dysfunction (reactive hyperemia - EndoPAT score \< 2.0) at time of screening

You may not qualify if:

• Serum potassium \> 5.0 mmol/L documented at any time prior to the study
• History of any cardiovascular event (stroke, transient ischemic attack (TIA), myocardial infarction (MI), unstable angina, coronary artery bypass grafting (CABG), percutaneous coronary intervention, hospitalization due to heart failure) during the 3 months prior to the study
• Hypertension or hypotension (at Randomization): any patient with Mean Seated Systolic Blood Pressure (msSBP) ≥ 170 mmHg, msSBP \< 100 mmHg or Mean Seated Diastolic Blood Pressure (msDBP) ≥ 110 mmHg
• Congestive heart failure New York Heart Association (NYHA) class III and IV
• Concomitant treatment with two (2) or more renin-angiotensin-aldosterone system blocking agents, e.g. Angiotensin Converting Enzyme Inhibitor (ACEI), Angiotensin II receptor blockers (ARB) or aldosterone-antagonist
• Unstable serum creatinine
• Second (II) or third (III) degree heart block without a pacemaker
• Concurrent potentially life threatening arrhythmia or other uncontrolled arrhythmia
• Clinically significant valvular heart disease
• Known renal artery stenosis
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of the study drugs including, but not limited to, any of the following:
• History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
• Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase
• Evidence of hepatic disease as determined by a history of hepatic encephalopathy, a history of cirrhosis, esophageal varices, or a history of portocaval shunt
• History of malignancy other than basal cell skin cancer within the past five years

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute on Aging (NIA): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Novartis: collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Flammer AJ, Gossl M, Li J, Reriani M, Shonyo S, Loeffler D, Herrmann J, Lerman LO, Lerman A. Renin inhibition with aliskiren lowers circulating endothelial progenitor cells in patients with early atherosclerosis. J Hypertens. 2013 Mar;31(3):632-5. doi: 10.1097/HJH.0b013e32835c6d2d. No abstract available.

  PMID: 23615219 DERIVED

MeSH Terms

Conditions

Atherosclerosis

Interventions

aliskiren

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Limitations and Caveats

The study was terminated early due to safety concerns from the ALTITUDE trial; there was an unexpected increase in adverse events (non-fatal stroke, renal complications, hyperkalemia and hypotension). Novartis ended all studies regarding Aliskiren.

Results Point of Contact

• Title: Dr. Amir Lerman
• Organization: Mayo Clinic

lerman.amir@mayo.edu

507-255-4152

Study Officials

• Amir Lerman, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 8, 2010
• First Posted: February 11, 2010
• Study Start: February 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: February 13, 2013
• Results First Posted: February 13, 2013

Record last verified: 2013-01

Locations

US (1)