Post Exercise Irisin Levels in PWS Patients
Primary Purpose
Prader Willi Syndrome
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
exercise and blood tests
Sponsored by
About this trial
This is an interventional diagnostic trial for Prader Willi Syndrome
Eligibility Criteria
Inclusion Criteria:
- Adult with Prader Willi syndrome
Exclusion Criteria:
- Inability to safely complete exercise regiment, heart disease or lungs disease
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Prader Willi syndrome
Obese controls
Arm Description
16 (8 males) PWS adolescents and young adults
16 - sex, age, and BMI-matched controls
Outcomes
Primary Outcome Measures
Number of Participants With Abnormal hormonal response
Secondary Outcome Measures
Full Information
NCT ID
NCT02728544
First Posted
February 17, 2016
Last Updated
April 4, 2016
Sponsor
Shaare Zedek Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT02728544
Brief Title
Post Exercise Irisin Levels in PWS Patients
Official Title
Post Exercise Irisin Levels in PWS Patients
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Unknown status
Study Start Date
April 2016 (undefined)
Primary Completion Date
September 2016 (Anticipated)
Study Completion Date
March 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shaare Zedek Medical Center
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prader Willi Syndrome
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Prader Willi syndrome
Arm Type
Experimental
Arm Description
16 (8 males) PWS adolescents and young adults
Arm Title
Obese controls
Arm Type
Active Comparator
Arm Description
16 - sex, age, and BMI-matched controls
Intervention Type
Other
Intervention Name(s)
exercise and blood tests
Intervention Description
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
Primary Outcome Measure Information:
Title
Number of Participants With Abnormal hormonal response
Time Frame
30 minutes
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Adult with Prader Willi syndrome
Exclusion Criteria:
Inability to safely complete exercise regiment, heart disease or lungs disease
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gross Tsur Varda, Prof.
Phone
972-2-6666239
Email
gros@szmc.org.il
First Name & Middle Initial & Last Name or Official Title & Degree
Badichi Nava, Research assistant
Phone
972-2-6666239
Email
navabad@szmc.org.il
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gross Tsur Varda, Prof.
Organizational Affiliation
Shaare Zedek Medical Center
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
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Post Exercise Irisin Levels in PWS Patients
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