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Feasibility Study of Simvastatin in Hodgkin's Lymphoma Survivors

Not Applicable
Terminated
Conditions
Carotid Artery Disease
Interventions
Registration Number
NCT00746603
Lead Sponsor
Columbia University
Brief Summary

Lay abstract: Study Purpose With contemporary combined modality therapy the expected longterm survival of children and adolescents with Hodgkin's disease (HD) is exceedingly high. Thus, the emphasis for future therapeutic interventions must include attention to the late effects of therapy. The development of cardiovascular disease as a late effect of radiation therapy has been well described and documented. Our recent pilot study of child and young adult HD survivors revealed significant subclinical atherosclerosis as evidenced by increased Carotid Artery Intima Media Thickness (CIMT) compared to controls. The higher CIMT values were positively associated with increasing age, total cholesterol, LDLcholesterol and diastolic BP. This finding was present in children and young adults who had received no or low dose radiation suggesting that chemotherapy or the disease process itself contributes to the development of atherosclerosis and risk for cardiovascular disease. Numerous studies have shown HMG CoA reductase inhibitors ("statins") to be effective in reducing the progression of atherosclerosis in adults. These agents have been studied in children and young adults for over a decade.

The primary aim of this study is:

To obtain pilot safety data on the use of simvastatin in young adults treated for HD.

The secondary aims of this study are:

To obtain pilot data on the effect of simvastatin on subclinical carotid artery atherosclerosis as measured by Carotid Artery IMT in young adults treated for HD.

To obtain pilot data on the effect of simvastatin on markers of inflammation measured in the serum of young adults treated for HD.

To obtain pilot data to serve as the basis for the development of a multicenter randomized study for the use of simvastatin in survivors of HD.

Detailed Description

With contemporary combined modality therapy the expected longterm survival of children and adolescents with Hodgkin's disease (HD) is exceedingly high. Thus, the emphasis for future therapeutic interventions must include attention to the late effects of therapy. The development of cardiovascular disease as a late effect of radiation therapy has been well described and documented. Our recent pilot study of child and young adult HD survivors revealed significant subclinical atherosclerosis as evidenced by increased Carotid Artery Intima Media Thickness (CIMT) compared to controls. The higher CIMT values were positively associated with increasing age, total cholesterol, LDLcholesterol and diastolic BP. This finding was present in children and young adults who had received no or low dose radiation suggesting that chemotherapy or the disease process itself contributes to the development of atherosclerosis and risk for cardiovascular disease. Numerous studies have shown HMG CoA reductase inhibitors ("statins") to be effective in reducing the progression of atherosclerosis in adults. These agents have been studied in children and young adults for over a decade.

The primary aim of this study is:

To obtain pilot safety data on the use of simvastatin in young adults treated for HD.

The secondary aims of this study are:

To obtain pilot data on the effect of simvastatin on subclinical carotid artery atherosclerosis as measured by Carotid Artery IMT in young adults treated for HD.

To obtain pilot data on the effect of simvastatin on markers of inflammation measured in the serum of young adults treated for HD.

To obtain pilot data to serve as the basis for the development of a multicenter randomized study for the use of simvastatin in survivors of HD.

We will do this by enrolling patients diagnosed with HD and evaluating the safety of simvastatin as evidenced by laboratory measures

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
3
Inclusion Criteria
  • At least three years from completion of treatment for Hodgkin's Disease
  • Age 18- 35
  • Ability to complete self report questionnaires in either English or Spanish
  • Willingness of patient, or parent/guardian if patient less than 18 years of age to sign consent to participate in study
  • Willingness of patient to sign assent if greater than 7 years of age and less than 18 years
Exclusion Criteria
  • Pregnant or breast feeding
  • Tanner Stage 1
  • Currently taking cyclosporine, niacin, antiretrovirals, macrolide antibiotic, azole antifungal
  • Liver enzymes greater than 1.5 times the upper level of normal
  • Creatine Kinase greater than 2 times the upper level of normal
  • Use of estrogen containing contraceptive

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
A Intervention ArmSimvastatinEscalating dose of simvastatin in subjects who are survivors of Hodgkin Lymphoma
Primary Outcome Measures
NameTimeMethod
Number of Participants Experiencing Grade 3 or Greater Muscle ToxicityUp to 26 weeks

Number of participants experiencing grade 3 or greater muscle toxicity as evaluated by creatinine kinase laboratory tests.

Number of Participants Experiencing Grade 3 or Higher Liver ToxicityUp to 26 Weeks

Number of participants experiencing grade 3 or higher liver toxicity as determined by liver function laboratory tests.

Change in Carotid Intima-media Thickness Test (CIMT)Up to 26 Weeks

A change in CIMT measurements ( measured in millimeters (mm)) will be performed.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Columbia Univeristy Medical Center

🇺🇸

New York, New York, United States

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