To identify some of the mechanisms in patients in remission of Cushing*s syndrome that contribute to the persistence of visceral obesity, systemic inflammation, insulin resistance, sarcopenia, a low muscle oxidative capacity and increased risk of…
ID
Source
Brief title
Condition
- Endocrine and glandular disorders NEC
- Musculoskeletal and connective tissue disorders NEC
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Physical fitness measured with an incremental cycling exercise test to
exhaustion (VO2max-test).
- Brachial %FMD levels as a marker of conduit artery endothelial function,
NO-mediated endothelium-(in)dependent vasodilation of the forearm resistance
arteries.
- Mitochondrial and capillary density, eNOS levels and eNOS phosphorylation,
NADPH oxidase activation, total JNK activity levels and expression of IKK* in
skeletal muscle cells.
- Amount of cytokines, adipokines and their mRNA and macrophage infiltration in
subcutaneous fat tissue.
Secondary outcome
-
Background summary
Cushing*s syndrome is the combination of signs and symptoms caused by
prolonged and inappropriately high exposure of tissue to glucocorticoids.
Chronic hypersecretion of cortisol causes central obesity, systemic
hypertension and glucose intolerance, sequentially leading to an increase in
cardiovascular morbidity and mortality in the active phase of the disease.
Patients in remission of CS remain to have a markedly impaired QOL and there
are multiple clear indications in literature that the increased cardiovascular
risk profile persists, even after long-term remission. However, all studies are
performed with small numbers of patients and results are contradictory.
Furthermore, the underlying mechanisms are poorly identified although there are
indications that persistence of visceral obesity, systemic inflammation,
insulin resistance, sarcopenia and a low muscle oxidative capacity play a role.
Study objective
To identify some of the mechanisms in patients in remission of Cushing*s
syndrome that contribute to the persistence of visceral obesity, systemic
inflammation, insulin resistance, sarcopenia, a low muscle oxidative capacity
and increased risk of cardiovascular disease in order to be able to target
future treatment strategies towards correction of these mechanisms.
Study design
This study is a cross-sectional matched case-control study.
Study burden and risks
Subjects will visit on three separate occasions. On the first visit an exercise
tolerance test will be performed. On the second visit a FMD-test and an
invasive vascular measurement will be performed. On the third visit muscle
biopsy and subcutaneous fat aspiration will be performed. The nature and extent
of burden and risks associated with the different tests are extensively
described in paragraph 10.3.
Eerste Oude Heselaan 118
6541PC
NL
Eerste Oude Heselaan 118
6541PC
NL
Listed location countries
Age
Inclusion criteria
- Subjects should be over 18 years old with the ability to read and comprehend the Dutch language
- Patients should be successfully cured for at least five years. Current remission should be confirmed by a recent 1mg dexamethasone suppression test
Exclusion criteria
- GH deficiency (This should be ruled out by an insulin tolerance test or an arginine/GHRH test) unless GH is properly supplemented (IGF-1 * 2)
- Serious co-morbidity (i.e. terminal malignancy, serious psychiatric pathology)
- Pregnancy
- Known diabetes mellitus
- Use of medication interfering with the cardiovascular system (ACE inhibitors, calcium antagonists, angiotensin II receptor antagonists) or adiponectins (thiazolidinediones)
- Severe cardiopulmonary disease as stated in the 2001 American heart association and 2002 American college of cardiology/American heart association guidelines
- Orthopedic and/or neurological diseases that impair exercise
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL39893.091.12 |