Feasibility Study of Simvastatin in Hodgkin's Lymphoma Survivors

Carotid Artery Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00746603
• Other study ID #: AAAB4447
• Status: Terminated
• Phase: N/A
• Start date: January 2008
• Est. completion date: July 2009

Study information

• Verified date: February 2021
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Carotid Artery Disease
• Carotid Artery Diseases

Intervention

Drug:
• Simvastatin
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.

Locations

Country	Name	City	State
United States	Columbia Univeristy Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	Children's Hospital of Philadelphia

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Change in Carotid Intima-media Thickness Test (CIMT)	A change in CIMT measurements ( measured in millimeters (mm)) will be performed.	Up to 26 Weeks