Desmopressin Stimulation Test Performance in ACTH-Dependent Cushing Syndrome

NCT06635629 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10001822001822-DK
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

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.

Conditions

Cushing Syndrome

Keywords

desmopressin, Cushing syndrome, diagnosis

Outcome Measures

Primary Outcomes (1)

• ACTH and cortisol responses

  Percent change from mean baseline values (-5, 0 minutes) at all combinations of dose dose timepoints

  -5, 0, 15, 30, 45 and 60 minutes

Secondary Outcomes (1)

• Diagnostic accuracy, specificity, sensitivity of cortisol and ACTH measurements in response to desmopressin

  -5, 0, 15, 30, 45 and 60 minutes

Study Arms (4)

Desmopressin 10 mcg Ad-lib fluid

OTHER

Desmopressin 10 mcg Ad-lib fluidHealthy volunteers only

Drug: Desmopressin

Desmopressin 10 mcg NPO

ACTIVE COMPARATOR

Desmopressin 10 mcg

Drug: Desmopressin

Desmopressin NPO 4 mcg

ACTIVE COMPARATOR

Desmopressin 4 mcg

Drug: Desmopressin

Dexmopressin 10 mcg NPO + Dexamethasone

ACTIVE COMPARATOR

Desmopressin 10 mcgDexamethasone 1 mg pretreatment

Drug: Desmopressin; Drug: Dexamethasone

Interventions

Desmopressin DRUG

Stimulates ACTH release in Cushing disease

Desmopressin 10 mcg Ad-lib fluid; Desmopressin 10 mcg NPO; Desmopressin NPO 4 mcg; Dexmopressin 10 mcg NPO + Dexamethasone

Dexamethasone DRUG

Inhibits ACTH release in Cushing disease and healthy volunteers

Dexmopressin 10 mcg NPO + Dexamethasone

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in this study, an individual must meet all of the following criteria:
• Aged 18-70 years
• Agreement to adhere to Lifestyle Considerations throughout the study.
• Evidence of acceptable laboratory testing results within four weeks of the first test day, as shown by medical record review:
• Hematocrit at entry \>=33 %
• Plasma sodium 136-145 mmol/L (unless taking a drug that can cause hyponatremia, see below) eGFR \>=60 ml/min/1.73 sq.m, calculated based on serum creatinine
• For subjects taking any drug that could worsen hyponatremia, a normal plasma sodium (136-145 mmol/L) must have been obtained within seven days of the first test day.
• In addition, an individual must meet all the criteria listed for their diagnostic group below, based on medical record review:
• A. Patients with possible ACTH-dependent Cushing Syndrome (where the results of further work up will classify the patient as having CD, EAS or pseudo-CS):
• A. Hypercortisolemia as evidenced by physician note or laboratory report: at least one screening modality (1 mg dexamethasone suppression test, 24-hour urinary free cortisol (UFC), bedtime or late night (2200h - 2359h) salivary or serum cortisol) within 4 weeks of screening. In patients suspected to have cyclic CS any previous abnormal result will suffice.
• A. Normal or increased plasma ACTH (\>20 pg/mL) as evidenced by physician note or laboratory report.
• B. Patients with recurrent ACTH-dependent Cushing Syndrome (previous CD or EAS):
• B. Evidence of previous remission of CD or EAS after resection of a causative pituitary or ectopic tumor, evidence of current ACTH-dependent hypercortisolism, and willingness to undergo repeat surgery.
• C. Healthy volunteers:
• C1. In good general health as evidenced by medical history and physical examination; and in a stable state of health without ongoing acute/temporary illness per the clinical judgement of the investigator.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study, based on medical record review (possible Cushing syndrome patients) or a screening visit (healthy volunteers).
• Inability to comply with all study procedures and visits
• Inability of subject to understand or to sign a written informed consent document.
• Known allergy/hypersensitivity to desmopressin.
• Pregnancy or lactation, due to alterations in measured serum cortisol and lack of data on desmopressin safety.
• A history of angina, significant coronary artery disease, congestive heart failure, or syndrome of inappropriate antidiuretic hormone secretion (SIADH), due to risk of fluid overload and/or hyponatremia.
• Uncontrolled hypertension (blood pressure \>150/95 mmHg) at screening and before desmopressin administration, due to risk of further increase if fluid overload occurs
• Any condition that in the opinion of the Investigator would jeopardize the participant s appropriate participation in this study.
• Current daily use of any of the following medications:
• Drug used for the stimulation tests: Desmopressin.
• Drugs that can suppress ACTH and cortisol test responses: Systemic glucocorticoids, including inhaled or topical formulations.
• Vasopressors: phenylephrine, dopamine and vasopressin.
• Drugs that interfere with desmopressin duration of action or potency: carbamazepine, lamotrigine, tolvaptan
• Strong inducers of CYP3A4 (e.g. barbiturates, phenytoin, rifampin, rifabutin, rifapentine, carbamazepine, eslicarbazepine, primidone, cenobamate, Modafinil). Use of St John's wort or nafcillin within 14 days.
• Initiation or dose increase within the past 14 days of drugs that can worsen hyponatremia: non-steroidal anti-inflammatory drugs (NSAIDs), loop diuretics (bumetanide, ethacrynic acid, furosemide, torsemide), chlorpromazine, chlorpropamide, cisplatin, monoamine oxidase inhibitors (MAOI), opiate agonists, oxybutynin, selective serotonin reuptake inhibitors (SSRI), vincristine, tricyclic antidepressants (TCAs)

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Cushing Syndrome; Disease

Interventions

Deamino Arginine Vasopressin; Dexamethasone

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Arginine Vasopressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Lynnette K Nieman, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Raven N McGlotten, R.N.

CONTACT

(301) 827-0190; mcglottenr@mail.nih.gov

Lynnette K Nieman, M.D.

CONTACT

(301) 496-8935; niemanl@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2024
• First Posted: October 10, 2024
• Study Start: December 12, 2024
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: May 4, 2026

Record last verified: 2026-04-29

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: Beginning 6 months after publication
• Access Criteria: The PI will review requests for data sharing. Data will shared for scientific analysis

Locations

US (1)