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Trial record 4 of 6 for:    PIK3CA Related Overgrowth Spectrum

Study of Proteus Syndrome and Related Congenital Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00001403
Recruitment Status : Recruiting
First Posted : November 4, 1999
Last Update Posted : July 30, 2020
Sponsor:
Collaborators:
Children's National Research Institute
Uniformed Services University of the Health Sciences
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )

Tracking Information
First Submitted Date November 3, 1999
First Posted Date November 4, 1999
Last Update Posted Date July 30, 2020
Actual Study Start Date April 27, 1994
Primary Completion Date Not Provided
Current Primary Outcome Measures
 (submitted: August 10, 2018)
  • Molecular delineation of disorders under study [ Time Frame: ongoing ]
    Determine causative genotypes of overgrowth disorders
  • Determination of natural history of disorders under study [ Time Frame: ongoing ]
    Determine natural history of a variety of overgrowth disorders
Original Primary Outcome Measures Not Provided
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Study of Proteus Syndrome and Related Congenital Disorders
Official Title The Phenotype and Etiology of Proteus Syndrome and Related Overgrowth Disorders
Brief Summary

This study will examine rare congenital disorders that involve malformations and abnormal growth. It will focus on patients with Proteus syndrome, whose physical features are characterized by overgrowth, benign tumors of fatty tissue or blood vessels, asymmetric arms or legs, and large feet with very thick soles. The study will explore the genetic and biochemical cause and course of the disease, the changes in symptoms over time, and the effects of the disease on patients.

Patients with Proteus syndrome and their parents may be eligible for this study. Parents will be studied, when possible, for comparison of molecular findings. Study candidates will have a medical history and physical examination, including X-rays and possibly other imaging tests, such as computerized tomography (CT), magnetic resonance imaging (MRI) and ultrasound. Other tests and examinations may be done if needed.

Those enrolled in the study will have will be interviewed or complete questionnaires, or both, about how their disease affects them. (Parents will be asked about their feelings about having a child with a rare disorder.) Patients will provide a small blood sample for research and may be asked to undergo biopsies from a normal area of skin and from a tumor.

Detailed Description The purpose of this project is to specifically delineate the phenotype and natural history and to better understand the genetic etiology of Proteus syndrome (PS) and other overgrowth disorders hypothesized to be in the AKT/PI3K pathway. As we have recently determined the molecular cause of PS and the related disorder of fibroadipose overgrowth, our main objectives moving forward include genotype-phenotype correlations, identifying quantifiable phenotypic characteristics in patients and measuring changes in these characteristics over time, developing potential biomarkers for future therapeutic research, and using our new molecular insights to expand our understanding of both PS and related overgrowth disorders. The natural history and specific phenotypic characteristics of patients with PS and selected other overgrowth disorders will be determined by clinical assessment and longitudinal followup of a cohort of patients. Subjects will be screened for eligibility using published diagnostic criteria for PS; screening for AKT1 and other pathway gene mutations may be used in patients with overlapping phenotypes. As well, we hope to identify and thoroughly phenotype a cohort of patients with molecularly-confirmed AKT1 mutations who may be candidates for future therapeutic intervention studies. The discovery of the AKT1 activating mutation in patients with this disease provides us with a very attractive pathway toward treatment for this devastating disorder. We also propose to expand our clinical ascertainment to determine the full range of PS/AKT1 activating mutation phenotypes and to study other overlapping conditions. The etiology of these disorders will be studied using candidate gene analysis (primarily based on the PI3K/AKT pathway) and possibly exome and whole genome sequencing (done under protocol 10-HG-0065).
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Patients with overgrowth syndromes and, occasionally, unaffected family members for control and genetic studies.@@@
Condition
  • Proteus Syndrome
  • PIK3CA Related Overgrowth Spectrum
Intervention Not Provided
Study Groups/Cohorts Proteus Syndrome
Patients with Proteus syndrome (PS) and other overgrowth disorders hypothesized to be in the AKT/PI3K pathway
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: June 23, 2005)
1500
Original Enrollment Same as current
Study Completion Date Not Provided
Primary Completion Date Not Provided
Eligibility Criteria
  • INCLUSION CRITERIA:

All patients who meet clinical diagnostic criteria for PS, or who have demonstrated AKT1 p.Glu17Lys mutations as well as their biological parents, are considered eligible for this protocol. As well, we will generally offer an in-person evaluation at the NIHCC to patients with PS whenever possible.

Patients with overgrowth that is not definitively PS (i.e., who do not appear to meet clinical diagnostic criteria) and their biological parents may also be eligible to participate in this study. Decisions to invite patients in this group to the NIHCC for an in-person evaluation are made on a case-by-case basis where the patient s phenotype, health, proximity to the NIH, and fit with our current research aims will all be taken into account. In general, we will consider subjects who have one or more of the manifestations from the PS clinical criteria as eligible.

There are no exclusions for race, age, or gender for participants.

EXCLUSION CRITERIA:

Patients with cancer but who do not have overgrowth or other non-tumor manifestations of PS or non-PS overgrowth, whose tumors may harbor AKT1, PIK3CA, or other mutations, are not eligible for this study. In general, patients who clearly meet diagnostic criteria for a well-characterized overgrowth syndrome that is NOT PS are not eligible for this study. Bannayan-Riley-Ruvalcaba syndrome and PHACES syndrome are examples of such entities. We have no plans to enroll prisoners, fetuses, pregnant women, healthy volunteers, or lab personnel. Some persons with PS and other overgrowth conditions are intellectually disabled (ID) or developmentally delayed (probably ~10%). The consent issues are no different for children with ID than developmentally appropriate children except that assent will be judged by developmental level instead of age. Probands who are adults and decisionally-impaired are eligible only if they have a legal guardian who has authority to sign a consent form on their behalf. Patients who are medically fragile or unable to tolerate travel to the NIHCC will not routinely be eligible for participation.

Since we enroll people of all ages, some of the women we enroll may become pregnant during the course of the study. No imaging studies will be done on women if they are known to be pregnant. No surgical procedures will be undertaken on pregnant women, and we will screen all women of reproductive age with a pregnancy test prior to surgery, as per standard surgical practice.

We will request permission to retain some information about prospective participants who may not be immediately enrolled. As these participants will not immediately be signing a consent form and joining the study, we propose to NOT count these participants in our Inclusion Enrollment Reports until they have formally enrolled in the study (that is, they have signed consent forms).

Sex/Gender
Sexes Eligible for Study: All
Ages up to 100 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Julie Sapp (301) 435-2832 sappj@mail.nih.gov
Contact: Leslie G Biesecker, M.D. (301) 402-2041 lesb@mail.nih.gov
Listed Location Countries United States
Removed Location Countries Germany
 
Administrative Information
NCT Number NCT00001403
Other Study ID Numbers 940132
94-HG-0132
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
Study Sponsor National Human Genome Research Institute (NHGRI)
Collaborators
  • Children's National Research Institute
  • Uniformed Services University of the Health Sciences
Investigators
Principal Investigator: Leslie G Biesecker, M.D. National Human Genome Research Institute (NHGRI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date July 20, 2020