Feasibility Study of Simvastatin in Hodgkin's Lymphoma Survivors

Study Overview
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Brief Summary
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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
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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

Official Title
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A Feasibility Study to Evaluate the Safety of Simvastatin in Young Adults Treated for Hodgkin's Disease

Conditions
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Carotid Artery Disease

Intervention / Treatment
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* Drug: Simvastatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A Intervention Arm<br>Escalating dose of simvastatin in subjects who are survivors of Hodgkin Lymphoma | Drug: Simvastatin<br>* All patients will start at 10mg of simvastatin, and then, based on results of interim evaluation escalated to 20mg and then 40. Patients will stay on maximally tolerated dose of drug until the end of the study at 26 weeks.<br>* Other names: Zocor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Grade 3 or Greater Muscle Toxicity | Number of participants experiencing grade 3 or greater muscle toxicity as evaluated by creatinine kinase laboratory tests. | Up to 26 weeks | 
| Number of Participants Experiencing Grade 3 or Higher Liver Toxicity | Number of participants experiencing grade 3 or higher liver toxicity as determined by liver function laboratory tests. | Up to 26 Weeks | 
| Change in Carotid Intima-media Thickness Test (CIMT) | A change in CIMT measurements ( measured in millimeters (mm)) will be performed. | Up to 26 Weeks |