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Post Exercise Irisin Levels in PWS Patients

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ClinicalTrials.gov Identifier: NCT02728544
Recruitment Status : Unknown
Verified March 2016 by Prof. V. Gross, Shaare Zedek Medical Center.
Recruitment status was:  Not yet recruiting
First Posted : April 5, 2016
Last Update Posted : April 5, 2016
Sponsor:
Information provided by (Responsible Party):
Prof. V. Gross, Shaare Zedek Medical Center

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.


Condition or disease Intervention/treatment Phase
Prader Willi Syndrome Other: exercise and blood tests Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Post Exercise Irisin Levels in PWS Patients
Study Start Date : April 2016
Estimated Primary Completion Date : September 2016
Estimated Study Completion Date : March 2017


Arm Intervention/treatment
Experimental: Prader Willi syndrome
16 (8 males) PWS adolescents and young adults
Other: exercise and blood tests
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

Active Comparator: Obese controls
16 - sex, age, and BMI-matched controls
Other: exercise and blood tests
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 Measures :
  1. Number of Participants With Abnormal hormonal response [ Time Frame: 30 minutes ]


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adult with Prader Willi syndrome

Exclusion Criteria:

  • Inability to safely complete exercise regiment, heart disease or lungs disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02728544


Contacts
Contact: Gross Tsur Varda, Prof. 972-2-6666239 gros@szmc.org.il
Contact: Badichi Nava, Research assistant 972-2-6666239 navabad@szmc.org.il

Sponsors and Collaborators
Shaare Zedek Medical Center
Investigators
Principal Investigator: Gross Tsur Varda, Prof. Shaare Zedek Medical Center

Responsible Party: Prof. V. Gross, neuropediateic, Shaare Zedek Medical Center
ClinicalTrials.gov Identifier: NCT02728544     History of Changes
Other Study ID Numbers: shaaraZMC
First Posted: April 5, 2016    Key Record Dates
Last Update Posted: April 5, 2016
Last Verified: March 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Prader-Willi Syndrome
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Obesity
Overnutrition
Nutrition Disorders