Desmopressin Stimulation Test Performance in ACTH-Dependent Cushing Syndrome

Desmopressin stimulation test performance in ACTH-Dependent Cushing Syndrome

ClinicalTrials.gov ID: NCT06635629
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by: National Institutes of Health Clinical Center (CC) (National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)) (Responsible Party)
Last Update Posted: 2024-11-18

Brief Summary
Background: Cushing syndrome (CS) is a set of diseases that develop when the body produces too much adrenocorticotropic hormone (ACTH). ACTH stimulates the production of a hormone called cortisol. Excess cortisol can cause serious issues, such as diabetes, high blood pressure, weight gain, and mood changes. Diagnosing CS early can be difficult. One test used to diagnose CS, the desmopressin (Desmo) stimulation test (DesmoST), has not been studied in enough people to know how accurate it is.

Objective: To find ways to improve the DesmoST. Researchers especially want to learn more about how well the DesmoST identifies people with specific ACTH CSs: Cushing disease (CD) and ectopic ACTH syndrome (EAS).

Eligibility: People aged 18 to 70 years who have or may have CS, especially CD or EAS. Healthy volunteers are also needed.

Design:
Participants with CS will have 3 DesmoSTs at least 48 hours apart. The procedure for each is as follows:

They will limit their fluid intake the day before each test. They will have nothing to eat or drink for 12 hours before the test.

For 1 of the tests, they will take a pill that contains a hormone (dexamethasone). They will take it around 11 pm the day before the test.

Desmo is given through a tube attached to a needle inserted into a vein.

Blood will be drawn a total of 6 times before and after the desmo is given.

Healthy volunteers will have 4 DesmoSTs. These will be 2 to 14 days apart.

All participants will have follow-up visits 3 to 5 days after each test. These visits may be by phone.

Detailed Description
Study Description: The goal of this study is to improve the diagnostic accuracy of the Desmopressin stimulation test (DesmoST) for three indications: to identify the etiology of ACTH-dependent Cushing syndrome (CS) as either Cushing Disease (CD) or Ectopic ACTH Syndrome (EAS), to discriminate between non-CS subjects (healthy controls and patients with pseudo-CS) and CD, and to identify CD in patients with cyclic hypercortisolism or recurrence. Test conditions include ad libitum water intake vs fluid restriction; increased glucocorticoid negative feedback (1 mg dexamethasone); and variable doses of desmopressin (4 mcg vs 10 mcg). We hypothesize that fluid restriction (via increased endogenous vasopressin levels), increased glucocorticoid negative feedback, and a lower dose of desmopressin improve specificity.

Objectives:
-Primary Objective:
To evaluate the hormonal response to desmopressin in subjects with ACTHdependent Cushing syndrome (CD and EAS) and non-CS subjects (healthy controls, pseudo-CS) under different conditions.

-Secondary Objective:
To evaluate the DesmoST performance (sensitivity, specificity, diagnostic accuracy) in identifying CD and distinguishing it from EAS and non-CS under different conditions.

-Exploratory Objectives:
To evaluate the ability of the DesmoST to identify CD in patients with cyclic hypercortisolism or postoperative recurrence; to evaluate whether Factor VIII is a biomarker for desmopressin action; and to explore the relationship between fluid status and response to desmopressin

Endpoints:
-Primary Endpoints:
Percentage change of peak ACTH and cortisol from baseline levels during the DesmoST under different conditions.

-Secondary Endpoints:
Cut-off points of relative ACTH and cortisol increase during the DesmoST that produce optimal diagnostic accuracy, once diagnostic information from other tests/imaging has been used to categorize subjects with suspected CS as having CD, EAS, or pseudo-CS.

-Exploratory Endpoints:
Percent change of peak ACTH and cortisol from baseline during the DesmoST in patients categorized as having cyclic hypercortisolism, postoperative recurrence, and fluid replete or restricted; the change in factor VIII levels after desmopressin administration.

Intervention / Treatment: 
- Drug: Desmopressin
- Drug: Dexamethasone

View full details