Cushing's Syndrome Before and After Treatment (CORRECT) (CORRECT)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cushing Syndrome
• Intervention / Treatment: Other: no intervention, as this is an observational study

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Simon Bøggild Hansen, MD; Phone Number: +45 41111574; Email: simhan@clin.au.dk
• Study Contact Backup: Name: Jens Otto Lunde Jørgensen, Professor; Email: joj@clin.au.dk

Study Locations

• Denmark
  • State
    • Aarhus, State, Denmark, 8200
      • Recruiting
      • Department of Endocrinology and Internal Medicine
      • Contact: Simon B Hansen, MD; Phone Number: 41111574; Email: simhan@clin.au.dk
      • Principal Investigator: Simon B Hansen, MD
      • Sub-Investigator: Jelena Stankovic, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with newly diagnosed Cushing's Syndrome

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

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 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 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
Change in Hba1C	Assessed as glycated hemoglobin A1C levels measured at three time points	Baseline, 3 months after and 1 year
Change in weight	Change in weight in kilograms	Baseline, 3 months after and 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in coagulation and inflammation markers in blood	Such as ADAM17 (Tumor necrosis factor-α-converting enzyme - TACE) Soluble CD16 (Human Low affinity immunoglobulin gamma Fc region receptor III-A) Fibrinogen vWF D-dimer Plasminogen, plasminogen activator inhibitor 1 Plasmin inhibitor	Baseline, 3 months after and 1 year
Change in metabolic and cardiovascular markers in blood	Such as plasma levels of Adiponectin, Leptin, Free fatty acids, cholesterol	Baseline, 3 months after and 1 year
Change in cytokines levels in blood	Such as Interleukin 6 Interleukin 10 Tumor necrosis factor alfa Transforming growth factor alfa Measured with cytokine luminex	Baseline, 3 months after and 1 year
Participant records: Number of infections, prescriptions for antibiotics	Assessed via electronic patient records	Baseline, 3 months after and 1 year

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital
• Investigators: Study Director: Jens Otto Lunde Jørgensen, Professor, AARHUS UNIVERSITY HOSPITAL, Medical Research Laboratory

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): November 1, 2032

Study Registration Dates

• First Submitted: August 16, 2022
• First Submitted That Met QC Criteria: August 26, 2022
• First Posted (Actual): August 30, 2022

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Quality of Life; Circadian Rhythm
• Additional Relevant MeSH Terms: Pathologic Processes; Endocrine System Diseases; Disease; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Syndrome; Cushing Syndrome
• Other Study ID Numbers: 1-10-72-41-22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No