Carotid Artery Disease
Conditions
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
Interventions
DRUGSimvastatin
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.
Sponsors
Children's Hospital of Philadelphia
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Grade 3 or Greater Muscle Toxicity | Up 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 Toxicity | Up 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. |
Countries
United States
Participant flow
Recruitment details
recruitment occurred in the late effects clinic
Participants by arm
| Arm | Count |
|---|---|
| Simvastatin Escalating dose of simvastatin
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. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Simvastatin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Change in Carotid Intima-media Thickness Test (CIMT)
A change in CIMT measurements ( measured in millimeters (mm)) will be performed.
Time frame: Up to 26 Weeks
Population: The study terminated in 2009 due to poor enrollment. The principal investigator (PI) and study team are no longer at the institution and the PI has confirmed that the data no longer exists. There are no data to report.
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.
Time frame: Up to 26 weeks
Population: The study terminated in 2009 due to poor enrollment. The principal investigator (PI) and study team are no longer at the institution and the PI has confirmed that the data no longer exists. There are no data to report.
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.
Time frame: Up to 26 Weeks
Population: The study terminated in 2009 due to poor enrollment. The principal investigator (PI) and study team are no longer at the institution and the PI has confirmed that the data no longer exists. There are no data to report.