Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05762549 |
| Other study ID # |
05L101 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 26, 2022 |
| Est. completion date |
May 31, 2024 |
Study information
| Verified date |
March 2023 |
| Source |
Istituto Auxologico Italiano |
| Contact |
Elisa Cairoli, MD |
| Phone |
390261911 |
| Email |
e.cairoli[@]auxologico.it |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The goals of this observational study are the following:
i) to assess the prevalence of hidden hypercortisolism (HidHyCo) in a sample of osteoporotic
patients; ii) to compare the clinical characteristics between osteoporotic/osteopenic
patients with HidHyCo and those without HidHyCo in order to determine the clinical
characteristics more frequently associated with the HidHyCo presence in the osteoporotic
population and to identify those osteoporotic patients worthy of HidHyCo screening.
In all patients who have been included in the study and who have given the informed consent
to participate in the study we will perform 1 mg overnight dexamethasone suppression test
(F-1mgDST).
In all subjects with F-1mgDST >1.8 mcg/dL, cortisol levels after two-day low dose (2 mg/day)
dexamethasone suppression test (F-2mgx2dDST) will be measured.
Patients with F-2mgx2dDST above >1.8 mcg/dL will be considered affected with HidHyCo and will
be managed following the available guidelines for hypercortisolism.
The HidHyCo could be present in a not negligible percentage of osteopenic/osteoporotic
patients. In these patients, osteoporosis and, if present, other comorbidities (i.e.
hypertension and/or diabetes) can improve by the surgical resection of the adrenal or
pituitary adenoma if feasible, or by the use of drugs able to modulate cortisol secretion or
glucocorticoid sensitivity.
Description:
Clinically overt hypercortisolism (i.e. Cushing's syndrome) leads to hypertension, central
obesity, diabetes and osteoporosis.
More recently, even the condition of mild and asymptomatic hypercortisolism has been
associated with increased prevalence of chronic complications of cortisol excess and
mortality. In patients with osteoporosis this form of hypercortisolism may remain occult
(hidden hypercortisolism, HidHyCo), until its presence is suspected on the basis of
particular characteristics of the underlying disease.
By definition, HidHyCo is a condition of cortisol excess in the absence of its classical
signs and symptoms. Although asymptomatic, however, this subtle cortisol excess is associated
with an increased risk of osteoporosis and fragility fractures.
Moreover, HidHyCo prevalence seems to be increased in osteoporotic patients. In particular,
the prevalence of HidHyCo in patients with low bone mineral density and with fragility
fracture has been reported to be 1.7-9.9% and 1.9-17.6%, respectively.
The HidHyCo case finding is of utmost importance since these patients experience an
impressive reduction of the fracture risk after the normalization of cortisol levels.
However, given the high prevalence of bone fragility and the relatively low diagnostic
accuracy of the currently available tests for the HidHyCo detection, a mass screening for
HidHyCo is considered unthinkable. Therefore, the issue of which osteoporotic patient has to
be screened for HidHyCo has recently become a widely debated topic, but as now, no guidelines
are available for addressing the HidHyCo screening in osteoporosis.
Therefore, the aims of the present study protocol are the following: i) to assess the HidHyCo
prevalence in a sample of osteoporotic patients; ii) to compare the clinical characteristics
between osteoporotic/osteopenic patients with HidHyCo and those without HidHyCo in order to
determine the clinical characteristics more frequently associated with the HidHyCo presence
in the osteoporotic population and to identify those osteoporotic patients worthy of HidHyCo
screening.
In all patients who have been included in the study and who have given the informed consent
to participate in the study the following vital and anthropometric parameters will be
recorded: blood pressure, heart rate, weight, height, body mass index (BMI), abdominal
circumference and waist-to-hip ratio. Moreover, the following variables will be collected:
familiar history of fragility fracture, smoking habit, main comorbidities, history of falls,
previous clinical fragility fractures, ongoing pharmacological treatment (in particular type
and number of antihypertensive, lipid lowering, anti-diabetic and anti-osteoporotic drugs),
previous anti-osteoporotic treatments, in females regularity of menses or age of menopause
and in males testosterone levels. Questionnaires for assessing daily calcium intake and
physical activity will be administered to all patients.
At the time of enrolment, the results of first tier investigations according to national
guidelines (i.e. serum erythrocyte sedimentation rate, complete blood count, serum protein
electrophoresis, serum calcium levels, serum phosphate levels, total alkaline phosphatase,
serum creatinine, 24-h urinary calcium) will be also registered. Moreover, other
calcium-phosphate metabolism parameters (i.e. serum ionized calcium, serum parathyroid
hormone, serum 25-OH-vitamin D, serum ß-CrossLaps, bone alkaline phosphatase) and routine
determinations (i.e. fasting glucose, insulin, glycated haemoglobin, total cholesterol, low
density lipoprotein, high density lipoprotein, triglycerides, transaminases) will be
recorded, if available.
According to the good clinical practice, in all patients bone mineral density will be
assessed by dual-energy X-ray Absorptiometry (Hologic or Lunar bone densitometers) and the
presence of asymptomatic vertebral fractures will be checked by conventional spinal
radiographs using the semi-quantitative visual assessment described by Genant et al., defined
as a reduction of >20% in anterior, middle, or posterior vertebral height.
Finally, iIn all patients who have been included in the study and who have given the informed
consent to participate in the study we will perform 1 mg overnight dexamethasone suppression
test (F-1mgDST). In all subjects with F-1mgDST >1.8 mcg/dL, cortisol levels after two-day low
dose (2 mg/day) dexamethasone suppression test (F-2mgx2dDST) will be measured.
Patients with F-2mgx2dDST above >1.8 mcg/dL will be considered affected with HidHyCo and will
be managed following the available guidelines for hypercortisolism.
The HidHyCo prevalence in osteopenic/osteoporotic patients and its 95% interval confidence
will be calculated.Then, we will compare the clinical and biochemical characteristics of
osteoporotic/osteopenic patients with HidHyCo and those without HidHyCo.
The sample size has been calculated in order to have an adequate number of HidHyCo cases to
determine the characteristics of osteoporotic patients suggestive for the presence of
HidHyCo. Since HidHyCo may be estimated to have at least a 3% prevalence in osteoporotic
patients, a sample of 1500 osteoporotic patients should be adequate to find no less than 45
HidHyCo cases.
Indeed, based on preliminary data, it is possible to assume that HidHyCo is present in a not
negligible percentage of osteopenic/osteoporotic patients.
The presence of osteoporosis associated with a poorly controlled hypertension and/or diabetes
or with a history of cardiovascular events (osteopenia with comorbidities) or the presence of
fragility fractures in the presence of not osteoporotic bone density, in an eugonadal state
and/or on osteoporotic treatment with bone-active drugs may be the variables potentially
associated with an increased probability of having HidHyCo.
By testing our sample of osteoporotic patients for HidHyCo, we aim at obtaining information
regarding the pre-test probability of a single individual of having a subtle cortisol excess
and, if feasible, at developing a clinical model for the identification in outpatient
osteoporosis clinics of subjects worthy of HidHyCo testing, thus avoiding a mass screening.
In HidHyCo patients, osteoporosis and, if present, other comorbidities (i.e. hypertension
and/or diabetes) can improve by the surgical resection of the adrenal or pituitary adenoma if
feasible, or by the use of drugs able to modulate cortisol secretion or glucocorticoid
sensitivity.
