Cushing's Syndrome Before and After Treatment (CORRECT)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to prospectively study patients with Cushing's syndrome before and after treatment, with a special emphasis on physical function, quality of life, and circadian rhythms. The hypotheses are: Cushing's syndrome negatively impacts health-related quality of life (HRQoL) and physical functioning Cushing's syndrome is associated with altered circadian rhythms at the whole body level and in peripheral target tissues. These complications partially reverse following disease control.

Official Title
-----------------
Effects of CORtisol Excess and REmission in Cushing's Syndrome Over Time (CORRECT): A Prospective Non-interventional Cohort Study

Conditions
-----------------
Cushing Syndrome

Intervention / Treatment
-----------------
* Other: no intervention, as this is an observational study


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: New (≤ 2 months) diagnosis of Cushing's syndrome (CS) of endogenous etiology: ACTH-dependent CS ACTH-independent CS Age >18 years Written informed consent Exclusion Criteria: Active cancer Iatrogenic or malignant cause of CS such as adrenocortical carcinoma Chronic heart failure (New York Heart Association class IV) Chronic kidney disease Chronic Kidney Disease stage ≥3 (eGFR >30 ml/min) Liver disease in the form of cirrhosis Deemed unable to complete the study safely by investigator

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: no intervention, as this is an observational study|no intervention|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CushingQoL-score | Questionnaire filled out by patients | Baseline, 3 months after and 1 year after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood pressure | Blood pressure, both standard office readings and as AOBP (Automated Office Blood Pressure) | Baseline, 3 months after and 1 year | 
| Change in arterial stiffness and endothelial function. | Arterial stiffness is assessed as Carotid-femoral PWV (cfPWV), measured using the SphygmoCor device (version 9; AtCor Medical | Baseline, 3 months after and 1 year | 
| Change in endothelial function. | Endothelial function will be assessed by the EndoPAT® device (Itamar Medical) | Baseline, 3 months after and 1 year | 
| Change in Insulin resistance | Assessed through fasting blood levels of insulin and glucose (Homeostasis Model Assessment, HOMA) | Baseline, 3 months after and 1 year | 
| Change in Hba1C | Assessed as glycated hemoglobin A1C levels measured at three time points | Baseline, 3 months after and 1 year | 
| Change in Messenger RNA expression of core clock genes in blood leukocytes and biopsies of skeletal muscle and adipose tissue. | Messenger RNA expression of core clock genes such as BMAL1, CLOCK, PER1-3, CRY1-2, REV-ERBα -β and -γ, RORA-C will be determined. For comparison, housekeeping genes such as Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), β2 microglobulin (B2M) and β-actin (ACTB) will be used. All will be expressed as -fold change from baseline expression levels | Baseline, 3 months after and 1 year | 
| Change in body composition | Dual X-ray absorptiometry (DXA), is used to measure whole body lean body mass, and fat mass in gram | Baseline, 3 months after and 1 year | 
| Change in Bone Mineral Density | Dual X-ray absorptiometry (DXA), bone mineral density (BMD) of the lumbar spine and femoral neck. | Baseline, 3 months after and 1 year | 
| Change in Vertebral Fracture Assessment | Dual X-ray absorptiometry (DXA), is used to assess vertebral fractures (VFA). | Baseline, 3 months after and 1 year | 
| Change in weight | Change in weight in kilograms | Baseline, 3 months after and 1 year | 
| Change in BMI | Height and weight are combined to express body mass index (BMI, kg/m2) | Baseline, 3 months after and 1 year | 
| Change in waist circumference | waist circumference is recorded with measuring tape. | Baseline, 3 months after and 1 year | 
| Change in hip circumference | Hip circumference is recorded with measuring tape. | Baseline, 3 months after and 1 year | 
| Change in Timed up and go (TUG)-test | The TUG Test combines measures of physical performance and coordination. The TUG test measures the time to stand up, walk 3 m in a straight line, and immediately return to the chair. The result is expressed as the fastest time in seconds | Baseline, 3 months after and 1 year | 
| Change in Short Physical Performance Battery (SPPB) and chair rising test - score | The short physical performance battery (SPPB) is a group of bed-side measures that combines the results of walking speed, chair stand and balance tests. The result is expressed as a collective score from 0-12 | Baseline, 3 months after and 1 year | 
| Change in Handgrip strength | Handgrip strength is measured using a hand dynamometer with the participant seated | Baseline, 3 months after and 1 year | 
| Change in total physical activity | Measured with an Actigraph tri-axial accelerometer on the non-dominant wrist. Expressed as Counts/day | Baseline, 3 months after and 1 year | 
| Change in Sedentary time | Measured with an Actigraph tri-axial accelerometer on the non-dominant wrist. Expressed as hours/day | Baseline, 3 months after and 1 year | 
| Change in total sleep time | Measured with an Actigraph tri-axial accelerometer on the non-dominant wrist. Expressed as hours/day | Baseline, 3 months after and 1 year | 
| Change in IPAQ-S7S | The questionnaire records types and intensity of physical activity and consists of seven open items | Baseline, 3 months after and 1 year | 
| FACS of blood leukocytes | Flow assisted cell sorting (FACS) will be performed on blood leukocytes followed by real time quantitative polymerase chain reaction on distinct cells or in single cell suspension from relevant tissue. | Baseline, 3 months after and 1 year | 
| Change in 24 hour urinary free cortisol | free cortisol | Baseline, 3 months after and 1 year | 
| Change in 24 hour urinary steroid metabolome | Steroid metabolome | Baseline, 3 months after and 1 year | 
| Change in 24 hour urinary adreneric metabolites | Adrenergic metabolites | Baseline, 3 months after and 1 year | 
| Change in Hospital Anxiety and Depression Scale (HADS) score | Questionnaire filled out by patients | Baseline, 3 months after and 1 year after treatment | 
| Change in Single item Sleep Quality Scale (SQS) score | Questionnaire filled out by patients | Baseline, 3 months after and 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Circadian Rhythm, Quality of Life