Statin Therapy in Young Adult Survivors of Childhood Cancer
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Peripheral Vascular Disease, Lymphoma |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Oncology |
| Healthy: | No |
| Age Range: | 18 - 39 |
| Updated: | 4/21/2016 |
| Start Date: | November 2012 |
| End Date: | March 2016 |
Pilot Study of Statin Therapy in Young Adult Survivors of Childhood Cancer
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.
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.
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.
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.
Inclusion Criteria:
- Survivor of childhood acute lymphoblastic leukemia (ALL) or non-Hodgkins's lymphoma
(NHL) (treated for ALL or NHL before the age of 21 years old and ≥5 years
post-treatment)
- 18-39 years old
Exclusion Criteria:
- Type 1 or 2 diabetes mellitus
- Prior treatment with hematopoietic stem cell transplant
- Low-density lipoprotein (LDL) -cholesterol ≥130 mg/dL (individuals with elevated
LDL-cholesterol will be referred for clinical management of dyslipidemia)
- Alanine transaminase (ALT), Aspartate transaminase (AST), or Creatine kinase (CK)
greater than 2 times the upper limit of normal
- Current or recent (within 6-months) use of lipid-lowering medication
- Recent initiation (within 6-months) of anti-hypertensive medication (individuals on
stable therapy may be enrolled)
- Current or recent (within 6-months) use of fibric acid derivatives, lipid-modifying
doses of niacin, cyclosporine or strong CYP3A4 inhibitors (i.e. clarithromycin, HIV
protease inhibitors, and itraconazole)
- Pregnant, lactating or planning to become pregnant
- Liver/renal dysfunction
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