Characteristics of Prader-Willi Syndrome and Early-onset Morbid Obesity

Prader-Willi Syndrome and Early-onset Morbid Obesity Natural History Clinical Protocol

Prader-Willi syndrome (PWS) is a rare genetic disorder that affects about 1 in 14,000 people in the United States. As the most commonly identified genetic cause of obesity, PWS is often confused with Early-onset Morbid Obesity (EMO). Individuals with EMO show some signs of PWS, but clinically do not have PWS. The purpose of this study is to evaluate the clinical features and genetic basis of PWS and EMO, and to determine how these conditions affect a person throughout a lifetime.

Study Overview

• Status: Completed
• Conditions: Obesity; Prader-Willi Syndrome
• Intervention / Treatment: Other: Group 1; Other: Group 2

Detailed Description

PWS is a complex neurobehavioral syndrome. Clinical features include obesity, increased appetite, low muscle tone, cognitive impairment, distinct behavioral features, hypogonadism, and neonatal failure-to-thrive. It is the most commonly recognized genetic cause of obesity; however, many obese children do not in fact have PWS. These individuals are therefore diagnosed with EMO, a condition that shares features with PWS. The development of new advances and strategies for treating PWS and EMO requires a thorough understanding of the conditions at both the clinical and molecular levels. One goal of this study is to collect long-term data on individuals with PWS and EMO in order to gain a better understanding of the natural progression of the conditions, from the neonatal period well into adulthood. Specific to PWS, this study will establish a genotype-phenotype correlation among the different sub-types and will evaluate the effects of growth hormone treatment on disease progression. Lastly, the study will compare PWS with EMO in terms of clinical features and genetic basis.

Participation in this natural history study will entail an initial evaluation, followed by yearly study visits until the age of 3 and then every 2 years thereafter. Each study visit will last between 3 and 4 hours, and will include a physical exam (including a DEXA scan to determine body composition), psychological testing, an interview with the study physician, and an evaluation of the participant's diet history. In addition, blood tests will be completed for genetic testing and photos will be taken to evaluate disease progression. Cognitive and behavioral assessments will also be conducted and will last between 10 and 30 minutes.

• Study Type: Observational
• Enrollment (Actual): 392

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • University of California at Irvine
  • Florida
    • Gainesville, Florida, United States, 32610-0296
      • University of Florida
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37201
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Individuals with Prader-Willi syndrome and Early-onset Morbid Obesity

Description

Inclusion Criteria:

• Individuals enrolling in the Prader-Willi syndrome group will have a confirmed diagnosis of Prader-Willi syndrome, as confirmed by molecular and cytogenetic testing
• Individuals enrolling in the Early-onset Morbid Obesity group will have a documented medical history of their weight exceeding 150% of the ideal body weight or a body mass index greater than 97% before the age of 4 years; they will also be under the age of 30 years.

Exclusion Criteria:

• Known genetic, chromosomal, or hormonal cause of cognitive impairment other than Prader-Willi syndrome

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; Individuals with Prader-Willi syndrome.	Other: Group 1; Individuals with Prader-Willi syndrome. Monitoring every 6 months.; Other Names: Prader-Willi syndrome; PWS
Group 2; Individuals with Early-onset Morbid Obesity	Other: Group 2; Individuals with Early-onset Morbid Obesity.; Other Names: PWS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phenotypic assessments of participants	phenotypic assessments will include cognitive level, behavioral analysis, physical features including body measurements and composition, co-morbidities (skin picking, psychiatric history, seizures, autistic behavior) medications required, and further comparison with the underlying molecular diagnosis.	until end of study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
longitudinal pattern of progression	assessment of cognition, behavior and body composition. In addition the age that growth hormone treatment began in the PWS participants will be correlated with physical features, body composition, cognition, behavior, developmental milestones, pubertal issues, and the onset of nutritional phases.	until end of study

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Rare Diseases Clinical Research Network; Office of Rare Diseases (ORD)
• Investigators: Study Chair: Arthur Beaudet, MD, Baylor College of Medicine

Publications and helpful links

General Publications

• Goldstone AP. Prader-Willi syndrome: advances in genetics, pathophysiology and treatment. Trends Endocrinol Metab. 2004 Jan-Feb;15(1):12-20. doi: 10.1016/j.tem.2003.11.003.
• Miller J, Kranzler J, Liu Y, Schmalfuss I, Theriaque DW, Shuster JJ, Hatfield A, Mueller OT, Goldstone AP, Sahoo T, Beaudet AL, Driscoll DJ. Neurocognitive findings in Prader-Willi syndrome and early-onset morbid obesity. J Pediatr. 2006 Aug;149(2):192-8. doi: 10.1016/j.jpeds.2006.04.013.
• Miller JL, Couch JA, Schmalfuss I, He G, Liu Y, Driscoll DJ. Intracranial abnormalities detected by three-dimensional magnetic resonance imaging in Prader-Willi syndrome. Am J Med Genet A. 2007 Mar 1;143A(5):476-83. doi: 10.1002/ajmg.a.31508.
• Butler MG. Management of obesity in Prader-Willi syndrome. Nat Clin Pract Endocrinol Metab. 2006 Nov;2(11):592-3. doi: 10.1038/ncpendmet0320. No abstract available.
• Butler MG, Bittel DC, Kibiryeva N, Talebizadeh Z, Thompson T. Behavioral differences among subjects with Prader-Willi syndrome and type I or type II deletion and maternal disomy. Pediatrics. 2004 Mar;113(3 Pt 1):565-73. doi: 10.1542/peds.113.3.565.
• Dykens E, Shah B. Psychiatric disorders in Prader-Willi syndrome: epidemiology and management. CNS Drugs. 2003;17(3):167-78. doi: 10.2165/00023210-200317030-00003.
• Miller J, Silverstein J, Shuster J, Driscoll DJ, Wagner M. Short-term effects of growth hormone on sleep abnormalities in Prader-Willi syndrome. J Clin Endocrinol Metab. 2006 Feb;91(2):413-7. doi: 10.1210/jc.2005-1279. Epub 2005 Nov 29.
• Shapira NA, Lessig MC, He AG, James GA, Driscoll DJ, Liu Y. Satiety dysfunction in Prader-Willi syndrome demonstrated by fMRI. J Neurol Neurosurg Psychiatry. 2005 Feb;76(2):260-2. doi: 10.1136/jnnp.2004.039024.
• Bittel DC, Butler MG. Prader-Willi syndrome: clinical genetics, cytogenetics and molecular biology. Expert Rev Mol Med. 2005 Jul 25;7(14):1-20. doi: 10.1017/S1462399405009531.
• Holsen LM, Zarcone JR, Brooks WM, Butler MG, Thompson TI, Ahluwalia JS, Nollen NL, Savage CR. Neural mechanisms underlying hyperphagia in Prader-Willi syndrome. Obesity (Silver Spring). 2006 Jun;14(6):1028-37. doi: 10.1038/oby.2006.118.
• Cassidy SB, Driscoll DJ. Prader-Willi syndrome. Eur J Hum Genet. 2009 Jan;17(1):3-13. doi: 10.1038/ejhg.2008.165. Epub 2008 Sep 10.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: September 11, 2006
• First Submitted That Met QC Criteria: September 11, 2006
• First Posted (Estimate): September 12, 2006

Study Record Updates

• Last Update Posted (Estimate): September 22, 2014
• Last Update Submitted That Met QC Criteria: September 18, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Early-onset Morbid Obesity
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Obesity; Obesity, Morbid; Prader-Willi Syndrome
• Other Study ID Numbers: RDCRN 5202; U54HD061222 (U.S. NIH Grant/Contract); ARP 5202 (Other Identifier: RDCRN)