WAGR SyndromeNCT00758108
Characterization of WAGR Syndrome and Other Chromosome 11 Gene Deletions
An observational study of WAGR Syndrome and Wilm's Tumor, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
This study will explore conditions caused by the absence of certain genes on chromosome 11. These conditions include WAGR syndrome, which is characterized by a kidney tumor called Wilm s tumor, aniridia (absence of the iris of the eye), genital and urinary abnormalities, mental retardation, and possibly other… Read more about this study
- Who is it for?
- Ages 2 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- WAGR Syndrome, Wilm's Tumor, Aniridia
- How many people
- 197 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Sep 2008to 29 Apr 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 99 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- For WAGR/11p deletion subjects:
- Diagnosis of WAGR/11p deletion confirmed by prior genetic testing or clinical history consistent with WAGR syndrome (Wilms Tumor and/or genitourinary anomalies plus aniridia). Genetic diagnosis will be confirmed at the NIH, if not done previously
- Age greater than or equal to 2 years old (Subjects age 2-6y will only have an outpatient evaluation, one 60 mL (or 5 mL/kg if weight <12 kg) blood draw, eye examination, and cognitive, behavioral, and psychiatric assessment performed; subjects age 6y and older will participate in full protocol)
- Medically stable (so that the patient can safely undergo planned testing); if history of Wilms tumor, must be >6 months since completion of chemotherapy and must be considered in remission by primary oncologist caring for the patient
- For parents of WAGR/11p deletion subjects:
- a)Biological parent of child with WAGR/11p deletion able to give consent for self participation
Show all 14Show fewer
- For healthy control subjects:
- Age greater than or eqaul to 2 years old (Subjects age 2-6y will only have an outpatient evaluation, one 60 mL (or 5 mL/kg if weight <12 kg) blood draw, and cognitive, behavioral, and psychiatric assessment performed; subjects age 6y and older will participate in full protocol)
- No chronic medications. Use of as-needed and over-the-counter medications will be reviewed on a case-by-case basis by the Principal Investigator
- No chronic medical or psychiatric conditions anticipated to affect results or impede study participation
- For aniridia subjects:
- Diagnosis of aniridia confirmed by ophthalmologist
- Age greater than or eqaul to 2 years old (Subjects age 2-6y will only have an outpatient evaluation, one 60 mL (or 5 mL/kg if weight <12 kg) blood draw, eye examination, and cognitive, behavioral, and psychiatric assessment performed; subjects age 6y and older will participate in full protocol)
- Medically stable, with no chronic medical or psychiatric conditions anticipated to affect results or impede study participation
Who cannot join
- For WAGR/11p deletion subjects:
- Anorexiant use in preceding 6 months
- Greater than 2% body weight loss in preceding 6 months
- Pregnancy
- Individuals who have, or whose parent or guardians have, current substance abuse or a psychiatric disorder or other condition which, in the opinion of the investigators, would impede competence or compliance or possibly hinder completion of the study
- For parents of WAGR/11p deletion subjects:
Show all 17Show fewer
- No exclusions other than lack of ability to give consent for participation
- For healthy control subjects:
- Anorexiant use in preceding 6 months
- Greater than 2% body weight loss in preceding 6 months
- Pregnancy
- Individuals who have, or whose parent or guardians have, current substance abuse or a psychiatric disorder or other condition which, in the opinion of the investigators, would impede competence or compliance or possibly hinder completion of the study
- For aniridia subjects:
- Anorexiant use in preceding 6 months
- Greater than 2% body weight loss in preceding 6 months
- Pregnancy
- Individuals who have, or whose parent or guardians have, current substance abuse or a psychiatric disorder or other condition which, in the opinion of the investigators, would impede competence or compliance or possibly hinder completion of the study
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: WAGR Syndrome and Other 11p Contiguous Gene Deletions: Clinical Characterization and Correlation With Genotype
This study will explore conditions caused by the absence of certain genes on chromosome 11. These conditions include WAGR syndrome, which is characterized by a kidney tumor called Wilm s tumor, aniridia (absence of the iris of the eye), genital and urinary abnormalities, mental retardation, and possibly other symptoms. This study will examine how the genes on chromosome 11 affect people and whether the absence of specific genes is associated with specific symptoms.
Healthy normal volunteers, people with isolated aniridia, and people with WAGR or another chromosome 11 gene deletion may be eligible for this study. Participants must be at least 6 years old. Parents of patients may also participate for genetic studies.
Read more
Participants undergo some or all of the following procedures, depending on whether they are a child, adult, healthy volunteer or parent of a patient:
- Medical history and physical examination, eye examination, blood, urine and saliva tests, electrocardiogram (EKG) and electroencephalogram (EEG)
- X-rays, scans and other tests to measure body composition (fat, muscle and bone development and thickness) and MRI to examine the eyes and the brain and to measure abdominal fat
- Ultrasound studies of the kidneys, ovaries and uterus (in females) and testes (in males)
- Meal tests, food diaries and food preference tests
- Questionnaires about eating and sleep habits, personality and character traits and responses to pain and injury
- Neuropsychological tests
- Tests of resting metabolic rate, energy expenditure and glucose (sugar) tolerance
- Hot and cold sensitivity tests, vibration sensitivity test, cold tolerance test and smell identification test
- Eye and hearing tests
- Nerve conduction studies and study of sensory information conduction from peripheral nerves to the spinal cord and brain
- Computer photography
- Evaluation by sub-specialists (e.g., endocrinologist, ophthalmologist, physiatrist, neurologist or others) as indicated by the patient s medical history and test results
Read the detailed description
WAGR syndrome is a rare genetic disorder characterized by Wilms tumor, aniridia, genitourinary anomalies and mental retardation. The syndrome is caused by heterozygous contiguous gene deletions of variable size on chromosome 11, involving a region that encompasses more than 100 genes, many of which have unknown function in humans. In our preliminary studies, we have observed that approximately two-thirds of patients with WAGR syndrome have deletion of the gene which encodes brain-derived neurotrophic factor (BDNF), and that BDNF haploinsufficiency is associated with obesity and with parent reports of hyperphagia and impaired nociception, suggesting that BDNF may play an important role in human energy balance as well as pain sensation. We now propose to conduct a comprehensive clinical phenotype-genotype study on patients with WAGR syndrome and other 11p deletions. We plan to enroll 75 subjects with WAGR syndrome/11p deletions who will undergo evaluations of the following systems: metabolic/endocrine, sensation/nociception, ophthalmologic, audiologic, neurocognitive, renal/genitourinary, oncologic, dental/craniofacial, cardiac, and orthopedic. Genetic testing will be performed on the parents of subjects with WAGR syndrome/11p deletion who choose to participate in order to determine if parental origin of the deletion influences phenotype. We also plan to enroll 75 healthy subjects as body-size matched controls for metabolic studies and 75 patients with isolated aniridia as visually impaired controls for neurocognitive studies. We hypothesize that a more complete understanding of the correlation between phenotype and genotype could lead to improved medical care of these patients through genotype-specific management as well as yield further insight into the physiological role of genes in the 11p region.
- Keywords
- Genotype/Phenotype Correlation, Energy Homeostasis, Nociception, Obesity, Behavior and Neurocognition, WAGR Syndrome, Wilm's Tumor, Aniridia, Mental Retardation, Urogenital Abnormalities, Healthy Volunteer
- Medical subject headings
- WAGR Syndrome, Wilms Tumor, Aniridia, Urogenital Abnormalities, Intellectual Disability, Obesity, Behavior
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2008 (estimated)
- Study start11 Sep 2008
- Study completion29 Apr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for WAGR SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Other
- Enrolment
- 197 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jack A Yanovski, M.D., Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00758108
- Sponsor's protocol ID
- 080213
- Other IDs
- 08-CH-0213
- Status last verified
- 29 Apr 2015
- First submitted
- 20 Sep 2008
- Last updated
- 12 Dec 2019
- Results posted
- No
Publications
Breslow NE, Norris R, Norkool PA, Kang T, Beckwith JB, Perlman EJ, Ritchey ML, Green DM, Nichols KE; National Wilms Tumor Study Group. Characteristics and outcomes of children with the Wilms tumor-Aniridia syndrome: a report from the National Wilms Tumor Study Group. J Clin Oncol. 2003 Dec 15;21(24):4579-85. doi: 10.1200/JCO.2003.06.096.
PubMed 14673045Fischbach BV, Trout KL, Lewis J, Luis CA, Sika M. WAGR syndrome: a clinical review of 54 cases. Pediatrics. 2005 Oct;116(4):984-8. doi: 10.1542/peds.2004-0467.
PubMed 16199712Pruunsild P, Kazantseva A, Aid T, Palm K, Timmusk T. Dissecting the human BDNF locus: bidirectional transcription, complex splicing, and multiple promoters. Genomics. 2007 Sep;90(3):397-406. doi: 10.1016/j.ygeno.2007.05.004. Epub 2007 Jul 12.
PubMed 17629449Sapio MR, Iadarola MJ, LaPaglia DM, Lehky T, Thurm AE, Danley KM, Fuhr SR, Lee MD, Huey AE, Sharp SJ, Tsao JW, Yanovski JA, Mannes AJ, Han JC. Haploinsufficiency of the brain-derived neurotrophic factor gene is associated with reduced pain sensitivity. Pain. 2019 May;160(5):1070-1081. doi: 10.1097/j.pain.0000000000001485.
PubMed 30855519Han JC, Reyes-Capo DP, Liu CY, Reynolds JC, Turkbey E, Turkbey IB, Bryant J, Marshall JD, Naggert JK, Gahl WA, Yanovski JA, Gunay-Aygun M. Comprehensive Endocrine-Metabolic Evaluation of Patients With Alstrom Syndrome Compared With BMI-Matched Controls. J Clin Endocrinol Metab. 2018 Jul 1;103(7):2707-2719. doi: 10.1210/jc.2018-00496.
PubMed 29718281
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- WAGR Syndrome and Other 11p Contiguous Gene Deletions: Clinical Characterization and Correlation With Genotype
- ClinicalTrials.gov ID
- NCT00758108
- Acronym / sponsor ID
- 080213
- Keywords
- Genotype/Phenotype Correlation, Energy Homeostasis, Nociception, Obesity, Behavior and Neurocognition, WAGR Syndrome, Wilm's Tumor, Aniridia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 197 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 11 Sep 2008
- Study completion
- 29 Apr 2015
- First posted
- 23 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will explore conditions caused by the absence of certain genes on chromosome 11. These conditions include WAGR syndrome, which is characterized by a kidney tumor called Wilm s tumor, aniridia (absence of the iris of the eye), genital and urinary abnormalities, mental retardation, and possibly other symptoms. This study will examine how the genes on chromosome 11 affect people and whether the absence of specific genes is associated with specific symptoms.
Healthy normal volunteers, people with isolated aniridia, and people with WAGR or another chromosome 11 gene deletion may be eligible for this study. Participants must be at least 6 years old. Parents of patients may also participate for genetic studies.
Participants undergo some or all of the following procedures, depending on whether they are a child, adult, healthy volunteer or parent of a patient:
- Medical history and physical examination, eye examination, blood, urine and saliva tests, electrocardiogram (EKG) and electroencephalogram (EEG)
- X-rays, scans and other tests to measure body composition (fat, muscle and bone development and thickness) and MRI to examine the eyes and the brain and to measure abdominal fat
- Ultrasound studies of the kidneys, ovaries and uterus (in females) and testes (in males)
- Meal tests, food diaries and food preference tests
- Questionnaires about eating and sleep habits, personality and character traits and responses to pain and injury
- Neuropsychological tests
- Tests of resting metabolic rate, energy expenditure and glucose (sugar) tolerance
- Hot and cold sensitivity tests, vibration sensitivity test, cold tolerance test and smell identification test
- Eye and hearing tests
- Nerve conduction studies and study of sensory information conduction from peripheral nerves to the spinal cord and brain
- Computer photography
- Evaluation by sub-specialists (e.g., endocrinologist, ophthalmologist, physiatrist, neurologist or others) as indicated by the patient s medical history and test results
Detailed description
WAGR syndrome is a rare genetic disorder characterized by Wilms tumor, aniridia, genitourinary anomalies and mental retardation. The syndrome is caused by heterozygous contiguous gene deletions of variable size on chromosome 11, involving a region that encompasses more than 100 genes, many of which have unknown function in humans. In our preliminary studies, we have observed that approximately two-thirds of patients with WAGR syndrome have deletion of the gene which encodes brain-derived neurotrophic factor (BDNF), and that BDNF haploinsufficiency is associated with obesity and with parent reports of hyperphagia and impaired nociception, suggesting that BDNF may play an important role in human energy balance as well as pain sensation. We now propose to conduct a comprehensive clinical phenotype-genotype study on patients with WAGR syndrome and other 11p deletions. We plan to enroll 75 subjects with WAGR syndrome/11p deletions who will undergo evaluations of the following systems: metabolic/endocrine, sensation/nociception, ophthalmologic, audiologic, neurocognitive, renal/genitourinary, oncologic, dental/craniofacial, cardiac, and orthopedic. Genetic testing will be performed on the parents of subjects with WAGR syndrome/11p deletion who choose to participate in order to determine if parental origin of the deletion influences phenotype. We also plan to enroll 75 healthy subjects as body-size matched controls for metabolic studies and 75 patients with isolated aniridia as visually impaired controls for neurocognitive studies. We hypothesize that a more complete understanding of the correlation between phenotype and genotype could lead to improved medical care of these patients through genotype-specific management as well as yield further insight into the physiological role of genes in the 11p region.
Study design
- Time perspective
- Other
Who may qualify
- Ages
- 2 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Diagnosis of WAGR/11p deletion confirmed by prior genetic testing or clinical history consistent with WAGR syndrome (Wilms Tumor and/or genitourinary anomalies plus aniridia). Genetic diagnosis will be confirmed at the NIH, if not done previously
- Age greater than or equal to 2 years old (Subjects age 2-6y will only have an outpatient evaluation, one 60 mL (or 5 mL/kg if weight <12 kg) blood draw, eye examination, and cognitive, behavioral, and psychiatric assessment performed; subjects age 6y and older will participate in full protocol)
- Medically stable (so that the patient can safely undergo planned testing); if history of Wilms tumor, must be >6 months since completion of chemotherapy and must be considered in remission by primary oncologist caring for the patient
- a)Biological parent of child with WAGR/11p deletion able to give consent for self participation
- Age greater than or eqaul to 2 years old (Subjects age 2-6y will only have an outpatient evaluation, one 60 mL (or 5 mL/kg if weight <12 kg) blood draw, and cognitive, behavioral, and psychiatric assessment performed; subjects age 6y and older will participate in full protocol)
Key exclusion criteria (17 listed)
- Anorexiant use in preceding 6 months
- Greater than 2% body weight loss in preceding 6 months
- Pregnancy
- Individuals who have, or whose parent or guardians have, current substance abuse or a psychiatric disorder or other condition which, in the opinion of the investigators, would impede competence or compliance or possibly hinder completion of the study
- No exclusions other than lack of ability to give consent for participation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2019.
- Background: PubMed 14673045Breslow NE, Norris R, Norkool PA, Kang T, Beckwith JB, Perlman EJ, Ritchey ML, Green DM, Nichols KE; National Wilms Tumor Study Group. Characteristics and outcomes of children with the Wilms tumor-Aniridia syndrome: a report from the National Wilms Tumor Study Group. J Clin Oncol. 2003 Dec 15;21(24):4579-85. doi: 10.1200/JCO.2003.06.096.
- Background: PubMed 16199712Fischbach BV, Trout KL, Lewis J, Luis CA, Sika M. WAGR syndrome: a clinical review of 54 cases. Pediatrics. 2005 Oct;116(4):984-8. doi: 10.1542/peds.2004-0467.
- Background: PubMed 17629449Pruunsild P, Kazantseva A, Aid T, Palm K, Timmusk T. Dissecting the human BDNF locus: bidirectional transcription, complex splicing, and multiple promoters. Genomics. 2007 Sep;90(3):397-406. doi: 10.1016/j.ygeno.2007.05.004. Epub 2007 Jul 12.
- Derived from this study: PubMed 30855519Sapio MR, Iadarola MJ, LaPaglia DM, Lehky T, Thurm AE, Danley KM, Fuhr SR, Lee MD, Huey AE, Sharp SJ, Tsao JW, Yanovski JA, Mannes AJ, Han JC. Haploinsufficiency of the brain-derived neurotrophic factor gene is associated with reduced pain sensitivity. Pain. 2019 May;160(5):1070-1081. doi: 10.1097/j.pain.0000000000001485.
- Derived from this study: PubMed 29718281Han JC, Reyes-Capo DP, Liu CY, Reynolds JC, Turkbey E, Turkbey IB, Bryant J, Marshall JD, Naggert JK, Gahl WA, Yanovski JA, Gunay-Aygun M. Comprehensive Endocrine-Metabolic Evaluation of Patients With Alstrom Syndrome Compared With BMI-Matched Controls. J Clin Endocrinol Metab. 2018 Jul 1;103(7):2707-2719. doi: 10.1210/jc.2018-00496.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jack A Yanovski, M.D. principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of WAGR Syndrome and Wilm's Tumor, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00758108, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2019.