Statin Therapy in Young Adult Survivors of Childhood Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Minnesota - Clinical and Translational Science Institute
Sponsor:
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01733953
First received: November 20, 2012
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Cardiovascular Disease
Childhood ALL
Childhood NHL
Drug: Atorvastatin
Drug: Sugar Pill (Placebo)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot Study of Statin Therapy in Young Adult Survivors of Childhood Cancer

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Change From Baseline in Brachial Artery Flow-Mediated Dilation at 6-months [ Time Frame: Baseline and 6-Months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline in Carotid Artery Compliance at 6-Months [ Time Frame: Baseline and 6-Months ] [ Designated as safety issue: No ]
  • Change from Baseline in Carotid Artery Distensibility at 6-Months [ Time Frame: Baseline and 6-Months ] [ Designated as safety issue: No ]
  • Change from Baseline in Pulse Wave Velocity at 6-Months [ Time Frame: Baseline and 6-Months ] [ Designated as safety issue: No ]
  • Change from Baseline in Augmentation Index at 6-Months [ Time Frame: Baseline and 6-Months ] [ Designated as safety issue: No ]
  • Change from Baseline in Carotid Intima-Media Thickness at 6-Months [ Time Frame: Baseline and 6-Months ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: November 2012
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atorvastatin
6-Months Atorvastatin Therapy; 40mg oral, once daily
Drug: Atorvastatin
6-Months of Atorvastatin (Lipitor); 40mg, oral, once daily.
Other Name: Lipitor
Placebo Comparator: Sugar Pill (Placebo)
6-Months Placebo (sugar pill); oral, once daily
Drug: Sugar Pill (Placebo)
6-Months of placebo (sugar) pill; oral, once daily
Other Name: Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 39 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01733953

Contacts
Contact: Cameron E Naughton, MPA 612-625-3623 naug0009@umn.edu

Locations
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Cameron E Naughton, M.P.A.    612-625-3623    naug0009@umn.edu   
Principal Investigator: Aaron S Kelly, Ph.D.         
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Investigators
Principal Investigator: Aaron S Kelly, Ph.D. University of Minnesota - Clinical and Translational Science Institute
  More Information

No publications provided

Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01733953     History of Changes
Other Study ID Numbers: 1207M17202
Study First Received: November 20, 2012
Last Updated: January 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
Cardiovascular Disease
Childhood ALL
Childhood NHL

Additional relevant MeSH terms:
Cardiovascular Diseases
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma
Atorvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014