Post Exercise Irisin Levels in PWS Patients
1 other identifier
interventional
32
0 countries
N/A
Brief Summary
Post exercise irisin levels in PWS patients Obesity, short stature, hypogonadism, hypotonia and impaired cognition are the major clinical features of Prader-Willi syndrome (PWS), a complex neurogenetic disorder due to lack of expression of paternal genes in the chromosomal region 15q11-13. Abnormal body composition with decreased muscle mass and increased fat mass contributes to low resting energy expenditure in PWS. Severe caloric restriction in the range of 800 kcal per day along with daily exercise regimens are needed to prevent weight gain and complications of obesity in this population. Brown adipose tissue (BAT) once thought to be present only in infants, but now known to be present in adults as well, differs from the more abundant white adipose tissue (WAT) by dissipating energy through thermogenesis as a result of increased activity of the mitochondrial uncoupling protein (UCP-1). Recently evidence shows that exercise activates mitochondrial UCP-1 in subcutaneous WAT cells resulting in conversion of WAT to BAT-like adipocytes (Beige or BRITE adipose tissue). Various factors including natriuretic peptides, interleukin-6 and myokines (irisin, fibroblast growth factor 21, and ß-aminoisobutyric acid) appear to mediate the effects of exercising muscle on subcutaneous adipocytes. Decreased amount and/or activity of BAT might contribute to the lower energy expenditure and extreme difficulty in weight-control in PWS. Lower levels or decreased myokine production could result in failure to convert subcutaneous WAT to Beige or BAT-like adipocytes, and therefore minimize or negate the otherwise beneficial metabolic effects of exercise. Direct measurement of peak oxygen uptake in PWS adults show that this population has markedly lower VO2 values compared with normal BMI-matched controls. BAT activity in vivo can be accurately measured only by performing PET/CT scans which include administrating radioactive tracers. For ethical reasons, direct assessment of BAT is not possible for purposes of clinical research in PWS individuals. The investigators propose to study humoral responses to exercise in 16 (8 males) PWS adolescents and young adults and compare results with responses in a similar number of sex, age, and BMI-matched controls. At an initial one-hour meeting study participants will learn to perform aerobic (treadmill) exercise and resistance training under the supervision of an experienced exercise physiologist. Exercise intensity will be assessed by direct measurement of VO2 max. On a different day, a blood sample will be drawn before and immediately at the conclusion of the same exercise regimen. Blood samples will be assayed for irisin, interleukin-6, atrial natriuretic peptide, FGF-21, in addition to glucose, growth hormone, cortisol, norepinephrine, and lactate. The investigators hypothesize that PWS participants will show weaker humoral responses to similar exercise regimens compared to normal control subjects. Data showing lower levels of myokines, such as irisin, following exercise in PWS might suggest that inadequate conversion of WAT to BAT-like adipocytes in subcutaneous adipose tissue results in decreased thermogenesis and abnormally low energy expenditure in this population. Potentially, development of pharmacologic agents which mimic irisin or other myokines by activating UCP-1 and converting WAT to BAT-like adipocytes could offer a new approach to weight-control in PWS individuals.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Apr 2016
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 17, 2016
CompletedStudy Start
First participant enrolled
April 1, 2016
CompletedFirst Posted
Study publicly available on registry
April 5, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2017
CompletedApril 5, 2016
March 1, 2016
5 months
February 17, 2016
April 4, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants With Abnormal hormonal response
30 minutes
Study Arms (2)
Prader Willi syndrome
EXPERIMENTAL16 (8 males) PWS adolescents and young adults
Obese controls
ACTIVE COMPARATOR16 - sex, age, and BMI-matched controls
Interventions
At an initial one-hour meeting study participants will learn to perform aerobic (treadmill) exercise and resistance training under the supervision of an experienced exercise physiologist. Exercise intensity will be assessed by direct measurement of VO2 m
Eligibility Criteria
You may qualify if:
- Adult with Prader Willi syndrome
You may not qualify if:
- Inability to safely complete exercise regiment, heart disease or lungs disease
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Gross Tsur Varda, Prof.
Shaare Zedek Medical Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- DIAGNOSTIC
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- neuropediateic
Study Record Dates
First Submitted
February 17, 2016
First Posted
April 5, 2016
Study Start
April 1, 2016
Primary Completion
September 1, 2016
Study Completion
March 1, 2017
Last Updated
April 5, 2016
Record last verified: 2016-03
Data Sharing
- IPD Sharing
- Will not share