Clinical Trial: Statin Therapy in Young Adult Survivors of Childhood Cancer

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Pilot Study of Statin Therapy in Young Adult Survivors of Childhood Cancer

Brief Summary:

Adult survivors of childhood cancer are at high risk of developing cardiovascular disease. Therapies used to treat many cancers, such as chemotherapy and radiation, likely cause damage to the surface of the artery wall called the endothelial layer, leading to the induction of atherosclerosis and eventual cardiovascular disease. HMG coenzyme A reductase inhibitors, or statins, improve endothelial function independent of cholesterol-lowering. In addition, statins have been shown to reduce arterial stiffness and slow arterial thickening. Despite strong evidence supporting the vascular benefits of statins in many different patient populations, these medications have never been studied in cancer survivors. Therefore, the overall objective of this study is to evaluate the effects of statin therapy on vascular health in young adult survivors of childhood cancer.

Twenty-four young adult (age 18-39 years old) survivors of childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) will be enrolled in a six-month randomized, double-blind (participants and investigators), placebo-controlled pilot clinical trial comparing the effects of atorvastatin versus placebo on endothelial function and other measures of vascular health.

Our primary objective is to evaluate the effects of 6-months of statin therapy on conduit artery endothelial function in young adult survivors of childhood cancer. The investigators hypothesize that, compared to placebo, atorvastatin will significantly increase brachial artery flow-mediated dilation in survivors of childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma.


Detailed Summary:

Adult survivors of childhood cancer are at seven times the risk of dying from cardiovascular disease compared to the general population. The increased risk is thought to be the result of the therapies used to treat the cancer such as chemotherapy and radiation. These therapies likely cause damage to the endothelial cells, which line the arterial wall and, when function properly, offer protection from atherosclerosis. Young adult survivors of childhood ALL have reduced endothelial function, or endothelial dysfunction, compared to healthy controls. Endothelial dysfunction is considered an early manifestation of atherosclerosis and therefore is an ideal target of therapy in order to reduce the risk of cardiovascular disease. Interventions that improve endothelial function in young adult survivors of childhood cancer may be beneficial in terms of mitigating the medium- and long-term risk of developing this chronic disease.

HMG coenzyme A reductase inhibitors, or statins, are widely used for cardiovascular disease risk reduction. These medications are primarily used to reduce levels of total- and low-density lipoprotein (LDL) -cholesterol. Meta-analyses have consistently demonstrated that statin therapy improves endothelial function in a wide array of patient populations. Beyond their well-described vascular benefits, statins are an attractive therapeutic option for cardiovascular disease risk reduction due to their strong safety profile.

Despite the clear potential for endothelial function improvement and cardiovascular risk reduction, statin therapy has never been evaluated in survivors of childhood cancer. Although statins have been well-studied in other patient populations at risk for cardiovascular disease, there is strong justification for evaluation in cancer survivors since the mechanisms responsible for the vascular pr
Sponsor: University of Minnesota - Clinical and Translational Science Institute

Current Primary Outcome: Change From Baseline in Brachial Artery Flow-Mediated Dilation at 6-months [ Time Frame: Baseline and 6-Months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change From Baseline in Carotid Artery Compliance at 6-Months [ Time Frame: Baseline and 6-Months ]
    Carotid Artery Compliance is a measure of arterial stiffness. Higher arterial stiffness places persons at higher risk for CVD.
  • Change From Baseline in Carotid Artery Distensibility at 6-Months [ Time Frame: Baseline and 6-Months ]
  • Change From Baseline in Pulse Wave Velocity at 6-Months [ Time Frame: Baseline and 6-Months ]
  • Change From Baseline in Augmentation Index at 6-Months [ Time Frame: Baseline and 6-Months ]
  • Change From Baseline in Carotid Intima-Media Thickness at 6-Months [ Time Frame: Baseline and 6-Months ]


Original Secondary Outcome:

  • Change From Baseline in Carotid Artery Compliance at 6-Months [ Time Frame: Baseline and 6-Months ]
  • Change From Baseline in Carotid Artery Distensibility at 6-Months [ Time Frame: Baseline and 6-Months ]
  • Change From Baseline in Pulse Wave Velocity at 6-Months [ Time Frame: Baseline and 6-Months ]
  • Change From Baseline in Augmentation Index at 6-Months [ Time Frame: Baseline and 6-Months ]
  • Change From Baseline in Carotid Intima-Media Thickness at 6-Months [ Time Frame: Baseline and 6-Months ]


Information By: University of Minnesota - Clinical and Translational Science Institute

Dates:
Date Received: November 20, 2012
Date Started: November 2012
Date Completion:
Last Updated: October 28, 2016
Last Verified: October 2016