Study of Brain and Spinal Cord Tumor Growth and Cyst Development in Patients With Von Hippel Lindau Disease

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Brief Title

Study of Brain and Spinal Cord Tumor Growth and Cyst Development in Patients With Von Hippel Lindau Disease

Official Title

A Prospective Natural History Study of VHL Patients With CNS Hemangioblastomas

Brief Summary

      The purpose of this study is to learn more about the growth of brain and spinal cord tumors
      and cysts that develop in association with them in patients with von Hippel-Lindau disease.
      It will examine how fast the tumors grow and try to determine what factors (for example,
      puberty , pregnancy, menopause, blood proteins, etc.) affect their growth.

      Patients between the ages of 8 and 75 years who are enrolled in NIH s study of von
      Hippel-Lindau disease may be eligible for this 5-year study. Participants will have magnetic
      resonance imaging (MRI) of the brain and spinal cord and a thorough neurological history and
      examination at the start of the study. A blood sample will be taken for analysis of factors
      (hormones or other proteins) that may predict tumor growth. Follow-up clinic visits every 6
      months will include a physical and neurological examination, blood tests, and MRI scans of
      the brain and spine. If symptoms or tumor growth requires more frequent follow-up, scans will
      be done at 3-month intervals.

      Surgical removal of brain and spinal cord tumors is currently the treatment of choice when
      these lesions cause neurological problems. A better understanding of which tumors are likely
      to grow and which will remain stable may help guide physicians in treatment decisions and
      avoid unnecessary procedures.

Detailed Description

      Hemangioblastomas of the cerebellum, brainstem and spinal cord are frequent tumors in
      patients with von Hippel-Lindau (VHL) disease. Rarely, these lesions also affect the
      cerebrum. Patients often have multiple lesions, many of which are associated with cysts or
      syrinx. The current treatment for symptomatic lesions is surgical resection. Focused
      radiation is also being used in selected cases in an attempt to provide tumor control. The
      natural history of central nervous system (CNS) lesions in patients with VHL has not been
      addressed in a prospective study. It is not clear at which point these lesions will begin to
      grow, or develop cysts in the cerebellum or syrinx in the spinal cord, and systemic factors
      that influence tumor growth have not been identified. By identifying factors that predict or
      influence tumor progression or cyst development, we can more accurately recommend surgical or
      medical intervention at appropriate times and avoid unnecessary treatment for stable lesions.
      This study will collect prospective radiological and clinical data on growth of the central
      nervous system (CNS) hemangioblastomas and associated cysts. We will also prospectively
      collect information on systemic processes that may influence tumor progression, such as
      puberty, menopause, pregnancy, effects of hormone therapy, tumor load, serum erythropoeitin
      level and hemoglobin/hematocrit levels.

      This natural history study has resulted in significant improvement in our understanding of
      the pathophysiology of VHL disease. Data from this study have resulted in a better
      understanding of the origin and growth patterns of hemangioblastomas, and endolymphatic sac
      tumors in patients with VHL disease. New therapies targeting hemangioblastomas in VHL disease
      are being devised based on information gathered from this study. We expect this natural
      history disease to continue to inspire new hypothesis driven studies while improving the
      understanding and management of hemangioblastomas in VHL disease.

Study Type


Primary Outcome

Determine the course of clinical and radiographic progression of VHL

Secondary Outcome

 Determine the course of tumor and cyst growth after surgical and/or radiation intervention.



Study Arms / Comparison Groups

Description:  250 subjects with von Hippel-Lindau (VHL) disease.


* 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


Start Date

February 15, 2001

Eligibility Criteria


               1. Ages 8-75.

               2. Confirmed diagnosis of von Hippel-Lindau disease.

               3. Presence of one or more cerebral, cerebellar or spinal cord hemangioblastomas on
                  screening MRI.

               4. Able to give informed consent (or assent), or have a parent able to provide
                  informed consent if a child.

               5. Karnofsky Performance Scale Score greater than or equal to 60.

               6. Have the capacity to undergo serial MRI scanning of the CNS without IV sedation.


          1. Clinically unstable condition.

          2. Being treated by any chemotherapy, immunotherapy, or steroids.

          3. Allergy to CT or MRI contrast agents.

          4. Contraindication to MRI scanning such as surgery that involves metal clips or wires
             which might be expected to cause tissue damage or produce image artifacts.




8 Years - 75 Years

Accepts Healthy Volunteers



Prashant Chittiboina, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Study Sponsor

Prashant Chittiboina, M.D., Principal Investigator, National Institute of Neurological Disorders and Stroke (NINDS)

Verification Date

May 18, 2022