Tuberous Sclerosis Complex Natural History Study: Renal Manifestations

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Brief Title

Tuberous Sclerosis Complex Natural History Study: Renal Manifestations

Official Title

Tuberous Sclerosis Complex Natural History Study: Renal Manifestations

Brief Summary

      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.
    

Detailed Description

      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.
    


Study Type

Observational




Condition

Tuberous Sclerosis Complex



Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

450

Start Date

February 2008

Completion Date

September 2013

Primary Completion Date

September 2013

Eligibility Criteria

        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
      

Gender

All

Ages

7 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

John J Bissler, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00598455

Organization ID

TS0500008

Secondary IDs

W81XWH-06-1-0538

Responsible Party

Sponsor

Study Sponsor

Children's Hospital Medical Center, Cincinnati

Collaborators

 Loma Linda University

Study Sponsor

John J Bissler, M.D., Principal Investigator, Children's Hospital Medical Center, Cincinnati


Verification Date

May 2017