Trial Information

Tuberous Sclerosis Complex Natural History Study: Renal Manifestations

Objectives.

Our objective is to test the hypothesis that serial MR and CT imaging will allow objective,
reproducible quantification of angiomyolipoma growth by volumetric analysis, and analysis of
lesions characteristics will identify angiomyolipomata with rapid growth potential that
would require intervention.

The specific aim of this proposal is to collect clinically obtained serial abdominal imaging
from the Tuberous Sclerosis Natural History Consortium Centers and analyze the volume and
adiposity of the individual angiomyolipomata. The growth rate is hypothesized to have an
inverse relationship to adiposity. The prognostic value of identifying lesions with
aggressive growth characteristics is very large, and intervention can be instituted early in
order to reduce the renal damage.

Study Population.

1. The target population for this study will be patients with tuberous sclerosis who
attend a tuberous sclerosis clinic that is part of the consortium. The data collected
will include routine imaging data, age, gender, and if know, the genotype.
Approximately 855 patients throughout the United States will be asked to participate in
this natural history study and 450 of those are anticipated to consent and have
complete data on 3 years of CT and MR Imaging Scans to measure angiomyolipoma growth
and adiposity.

2. Patients attending the tuberous sclerosis clinics that are members of the consortium
will be asked if they would be involved in the study.

3. Imaging will be obtained as part of the standard of care at the Consortium Centers.
Imaging done on pregnant patients will not be excluded. MRI has been used now
extensively for pregnant patients.

Protocol Design.

This is a natural history study involving the imaging characteristics of angiomyolipomata
found in patients with tuberous sclerosis complex. This study offers the potential benefit
that the lesion characteristics and growth rate will be monitored. Patel et al. posit that
growth rates of greater than 0.5 cm/year for solid tumors are worrisome for malignancy.
Patients harboring lesions that exhibit faster growth rates will be identified so that they
can be more carefully monitored. During the course of the study, should we detect
concerning features, the Consortium Center TS Clinic Director will be alerted. Imaging
modalities that may be used include CT scans. The patient data being collected will be done
so for clinical reasons, and every effort will be made to use the least possible radiation
exposure. There are several ways to reduce the exposure, and these limiting techniques will
be employed for each scan. The scans will be performed both pre and post contrast using an
agent such as Optiray® so that vascularity can be assessed. Patients may also be imaged
with a 1.5 Tesla magnet in a supine position using a phased array torso coil or body coil,
depending on patient size. When compatible, respiratory compensation will be used to
diminish respiratory artifact. Overall imaging time for the following sequences will be
approximately 45 minutes.

a. Recruitment process: Patients will be recruited from patients seen at the Tuberous
Sclerosis Natural History Consortium Centers, including Cincinnati Children's Hospital, Loma
Linda University, University of Pennsylvania Medical Center, Connecticut Children's Medical
Center, Vanderbilt University, Columbus Children's, Texas Scottish Rite Hospital,
Massachusetts General Hospital, Miami Children's Hospital, Minnesota Epilepsy Group,
Dartmouth University, Washington Children's Hospital, New York University School of
Medicine, University of Texas, Houston, Children's Hospital, Boston, and Children's
Hospital, Pittsburgh.