Statin Therapy in Young Adult Survivors of Childhood Cancer
Condition: Cardiovascular Disease; Childhood ALL; Childhood NHL
MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma; Cardiovascular Diseases
Study type: Interventional
Phase: Phase 2

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 description: 
      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 problems in these individuals (treatment-induced
      vascular toxicity) differ from traditional atherosclerosis. Therefore, the objective of the
      current study is to assess the ability of statin therapy to improve endothelial function,
      arterial stiffness, and arterial thickening in young adult survivors of childhood cancer. The
      focus of the study will be on survivors of hematologic malignancies, acute lymphoblastic
      leukemia (ALL) and non-Hodgkin's lymphoma (NHL), since the former has been shown to be
      associated with endothelial impairments and both cancers share common treatment exposures
      (chemotherapy and radiation), which is likely the primary factor responsible for endothelial
      dysfunction in these individuals.

      Twenty-four young adult (age 18-39 years old) survivors of childhood acute lymphoblastic
      leukemia (ALL) and 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. Following baseline testing, subjects will be randomly assigned
      (1:1) to either atorvastatin or placebo. Participants will return at 1-month and 3-months for
      assessment of safety (blood draw and adverse event assessment) and medication compliance and
      at 6-months for assessment of safety, medication compliance, and reassessment of baseline
      variables.
    

Intervention name(s): Atorvastatin; Sugar Pill (Placebo)
Intervention type(s): Drug; Drug
Intervention description(s): 6-Months of Atorvastatin (Lipitor); 40mg, oral, once daily.; 6-Months of placebo (sugar) pill; oral, once daily
Other intervention name(s): Lipitor; Placebo
Intervention MeSH terms: Atorvastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Cardiovascular Disease; Childhood ALL; Childhood NHL