Tuberous Sclerosis Complex Natural History Study: Renal Manifestations
| Status: | Completed |
|---|---|
| Conditions: | Neurology |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | 7 - 65 |
| Updated: | 4/2/2016 |
| Start Date: | February 2008 |
| End Date: | December 2012 |
| Contact: | John Bissler, M.D. |
| Email: | john.bissler@cchmc.org |
| Phone: | 513-636-1201 |
Eighty percent of patients with tuberous sclerosis complex (TSC) have renal
angiomyolipomata. These lesions grow and can lead to significant morbidity by hemorrhage or
renal failure. Understanding the natural history of these lesions and understanding which
lesions may be more prone to grow quickly or develop aneurysms that predispose to hemorrhage
will greatly assist clinical care of patients with TSC. The 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. Yearly renal MR or CT imaging will be performed of
patients with TSC. The images will be coded at the site of acquisition, and transferred via
VPN to a secure server at Cincinnati Children's Hospital Medical Center. Using innovative
imaging processing software (Cincinnati Children's Hospital Image Processing Software
(CCHIPS), the image data will be segmented to reveal various tissue components based on
signal intensities. Different signal intensities can differentiate normal renal parenchyma,
and renal angiomyolipomata. Using the imaging data and the novel software, the volume of an
individual angiomyolipoma, as well as the adiposity will be determined. Imaging at
enrollment (year 1) will serve as baseline. At years two and three, the lesions will undergo
repeat analysis. Angiomyolipoma growth rates and adiposity over three years will be analyzed
to test the hypothesis above.
angiomyolipomata. These lesions grow and can lead to significant morbidity by hemorrhage or
renal failure. Understanding the natural history of these lesions and understanding which
lesions may be more prone to grow quickly or develop aneurysms that predispose to hemorrhage
will greatly assist clinical care of patients with TSC. The 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. Yearly renal MR or CT imaging will be performed of
patients with TSC. The images will be coded at the site of acquisition, and transferred via
VPN to a secure server at Cincinnati Children's Hospital Medical Center. Using innovative
imaging processing software (Cincinnati Children's Hospital Image Processing Software
(CCHIPS), the image data will be segmented to reveal various tissue components based on
signal intensities. Different signal intensities can differentiate normal renal parenchyma,
and renal angiomyolipomata. Using the imaging data and the novel software, the volume of an
individual angiomyolipoma, as well as the adiposity will be determined. Imaging at
enrollment (year 1) will serve as baseline. At years two and three, the lesions will undergo
repeat analysis. Angiomyolipoma growth rates and adiposity over three years will be analyzed
to test the hypothesis above.
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.
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.
Inclusion Criteria:
- Patients who receive yearly follow-up at their respective tuberous sclerosis clinic.
Such clinics have a director who is knows their patients well.
- Patients known to have an angiomyolipoma between the ages of 7-
- 65 years
- Pregnant women to be included if tested with MR
Exclusion Criteria:
- Patients who are not seen annually and therefore do not have yearly imaging.
- Patients who do not have an angiomyolipoma.
- Patients who are not likely to follow-up as recommended.
- Use of an investigational drug, including rapamycin, within the last 30 days.
- Pregnant women to be excluded if they cannot be tested with MR
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