- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00001403
Study of Proteus Syndrome and Related Congenital Disorders
The Phenotype and Etiology of Proteus Syndrome
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.
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Study Overview
Status
Detailed Description
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Julie Sapp
- Phone Number: (301) 435-2832
- Email: sappj@mail.nih.gov
Study Contact Backup
- Name: Leslie G Biesecker, M.D.
- Phone Number: (301) 402-2041
- Email: lesb@mail.nih.gov
Study Locations
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Maryland
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Bethesda, Maryland, United States, 20892
- Recruiting
- National Institutes of Health Clinical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
- INCLUSION CRITERIA:
All patients who meet clinical diagnostic criteria for PS, or who have demonstrated AKT1 p.Glu17Lys mutations 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.
As these disorders are usually apparent at or soon after birth, and appear to evolve at least into the third decade of life, early assessment and long-term follow-up are necessary. We have already learned that PS has a high pediatric mortality rate. PS and other overgrowth disorders are progressive and for some individuals, may warrant more frequent observation during youth and adolescence. Therefore, it would not be practicable or ethical to exclude children from enrollment.
Patients with overgrowth that is not definitively PS (i.e., who do not appear to meet clinical diagnostic criteria) 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.
Enrollment of adults with impaired decision-making capacity is scientifically justified because PS is an ultra-rare disorder where 10-15% of patients have significant cognitive impairment and gaining a better understanding of this aspect of the phenotype (as well as the other concerns adult patients may present with) is critical to advancing our knowledge of this disorder. Progression of overgrowth, particularly the fibroadipose overgrowth in CLOVES syndrome, is a significant issue in many adults with this condition and understanding the trajectory of overgrowth throughout the lifespan is an important goal of this study.
This protocol enrolls participants of all ages which includes women of child-bearing age. We recognize that women may become pregnant during the course of this study. While we have not documented a case of a female with Proteus syndrome becoming pregnant it is important to gather clinical data if such a case occurs in order to better understand the natural history of Proteus syndrome and related disorders.
Since we enroll people of all ages, some of the women we enroll may become pregnant during the course of the study. No radiation imaging studies will be done on women if they are known to be pregnant. We will screen all women of reproductive age with a pregnancy test prior to surgery, as per standard surgical practice.
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 will not enroll prisoners, 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. Patients 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.
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).
We will not enroll neonates (newborns less than one month old).
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
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Proteus Syndrome
Patients with Proteus syndrome (PS) and other overgrowth disorders hypothesized to be in the AKT/PI3K pathway
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Molecular delineation of disorders under study
Time Frame: ongoing
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Determine causative genotypes of overgrowth disorders
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ongoing
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Determination of natural history of disorders under study
Time Frame: ongoing
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Determine natural history of a variety of overgrowth disorders
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ongoing
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Leslie G Biesecker, M.D., National Human Genome Research Institute (NHGRI)
Publications and helpful links
General Publications
- Keppler-Noreuil KM, Burton-Akright J, Kleiner DE, Sapp JC, Lindhurst MJ, Han CG, Biesecker LG, Gochuico BR. Phenotypic Features of Cystic Lung Disease in Proteus Syndrome: A Clinical Trial. Ann Am Thorac Soc. 2022 Nov;19(11):1871-1880. doi: 10.1513/AnnalsATS.202111-1214OC.
- Ours CA, Sapp JC, Hodges MB, de Moya AJ, Biesecker LG. Case report: five-year experience of AKT inhibition with miransertib (MK-7075) in an individual with Proteus syndrome. Cold Spring Harb Mol Case Stud. 2021 Dec 9;7(6):a006134. doi: 10.1101/mcs.a006134. Print 2021 Dec.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion
Study Completion
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Infections
- Neoplasms
- Disease
- Congenital Abnormalities
- Musculoskeletal Diseases
- Gram-Negative Bacterial Infections
- Bacterial Infections
- Bacterial Infections and Mycoses
- Bone Diseases
- Musculoskeletal Abnormalities
- Abnormalities, Multiple
- Enterobacteriaceae Infections
- Bone Diseases, Developmental
- Limb Deformities, Congenital
- Hamartoma Syndrome, Multiple
- Hamartoma
- Neoplasms, Multiple Primary
- Syndrome
- Proteus Infections
- Proteus Syndrome
Other Study ID Numbers
- 940132
- 94-HG-0132
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Proteus Syndrome
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Merck Sharp & Dohme LLCActive, not recruitingPIK3CA-Related Overgrowth Spectrum (PROS)/Proteus Syndrome (PS)United States, Australia, Brazil, Italy, United Kingdom
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ArQule, Inc. (a wholly owned subsidiary of Merck...Worldwide Clinical TrialsTerminatedPIK3CA-Related Overgrowth Spectrum (PROS)/Proteus SyndromeUnited States, Australia, Italy, Spain
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National Human Genome Research Institute (NHGRI)CompletedProteus SyndromeUnited States
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National Human Genome Research Institute (NHGRI)Recruiting
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Hamad Medical CorporationCompletedEscherichia Coli Bacteremia | Klebsiella Bacteraemia | Enterobacter Bacteraemia | Serratia Bacteraemia | Citrobacter Bacteraemia | Proteus BacteraemiaQatar, Turkey, Bahrain, Kuwait
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National Human Genome Research Institute (NHGRI)CompletedCoronary Artery Disease | Proteus Syndrome | Familial Isolated Hyperparathyroidism | Coffin - Sins Syndrome | Dubouitz SyndromeUnited States
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ArQule, Inc. (a wholly owned subsidiary of Merck...No longer availableGrowth Disorders | Proteus Syndrome | PIK3CA-Related Overgrowth Spectrum (PROS)
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University of PittsburghCompletedInfection | Proteus Infections | Klebsiella Infections | E Coli InfectionsUnited States
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Neumedicines Inc.Department of Health and Human ServicesCompletedHematopoietic Syndrome Due to Acute Radiation SyndromeUnited States
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Ministry of Public Health, Democratic Republic...National Institutes of Health (NIH); Oregon Health and Science University; National... and other collaboratorsCompletedNeurotoxicity Syndrome, Cassava | Neurotoxicity Syndrome, Cyanate | Neurotoxicity Syndrome, Cyanide | Neurotoxicity Syndrome, ThiocyanateCongo, The Democratic Republic of the