This study is currently recruiting participants.
Number
001822-DK
Sponsoring Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: 70 Years
Referral Letter Required
No
Population Exclusion(s)
Adults who are or may become unable to consent;Children;Fetuses;Pregnant Women
Keywords
desmopressin, Cushing syndrome, diagnosis
Recruitment Keyword(s)
None
Condition(s)
Cushing Syndrome
Investigational Drug(s)
Desmopressin Acetate Dexamethasone
Investigational Device(s)
Intervention(s)
Drug: Desmopressin Drug: Dexamethasone
Supporting Site
National Institute of Diabetes and Digestive and Kidney Diseases
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.
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INCLUSION CRITERIA: 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: -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): --Evidence of hypercortisolemia based on 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. --Evidence of normal or increased plasma ACTH (>20 pg/mL) -Patients with recurrent ACTH-dependent Cushing Syndrome (previous CD or EAS): --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. -Healthy volunteers: --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. EXCLUSION CRITERIA: 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 -Daily use of strong inducers of CYP3A4 (e.g. barbiturates, phenytoin, rifampin, rifabutin, rifapentine, carbamazapine, 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) -Chronic enhanced hydration (estimated as >4 liters) to supplement mealtime fluid intake. -Any contraindication to intravenous catheter use. -Previous participation in this protocol. - History of hemophilia of any type. -Any hematology or chemistry screening laboratory value drawn at screening that the Investigator determines is clinically significant for exclusion. Condition-specific exclusions will also apply to each subject group as follows: -Patients with possible ACTH-dependent Cushing Syndrome: --Use of medications that block glucocorticoid production or action within the past two weeks-ketoconazole, levoketoconazole, metyrapone, osilodrostat or mifepristone. --Use of the adrenolytic mitotane at any point, due to its prolonged half-life. --Use of medications that block ACTH release within the past two weeks - cabergoline, octreotide (subcutaneous), pasireotide (subcutaneous), megestrol acetate, other synthetic glucocorticoids (except for topical or inhaled agents) -Use of intramuscular long-acting forms of octreotide or pasireotide within the past 4 months. --Treatment of diabetes insipidus. -Healthy volunteers: --Use of oral, injectable, or inhaled glucocorticoids (unless intermittent, for symptomatic asthma) within the last year. Use of topical non-hydrocortisone containing potent glucocorticoids on more than 36 square inches in the last six months. --Hemoglobin A1c >= 6.5% on screening labs.
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:
-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):
--Evidence of hypercortisolemia based on 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.
--Evidence of normal or increased plasma ACTH (>20 pg/mL)
-Patients with recurrent ACTH-dependent Cushing Syndrome (previous CD or EAS):
--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.
-Healthy volunteers:
--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.
EXCLUSION CRITERIA:
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
-Daily use of strong inducers of CYP3A4 (e.g. barbiturates, phenytoin, rifampin, rifabutin, rifapentine, carbamazapine, 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)
-Chronic enhanced hydration (estimated as >4 liters) to supplement mealtime fluid intake.
-Any contraindication to intravenous catheter use.
-Previous participation in this protocol.
- History of hemophilia of any type.
-Any hematology or chemistry screening laboratory value drawn at screening that the Investigator determines is clinically significant for exclusion.
Condition-specific exclusions will also apply to each subject group as follows:
-Patients with possible ACTH-dependent Cushing Syndrome:
--Use of medications that block glucocorticoid production or action within the past two weeks-ketoconazole, levoketoconazole, metyrapone, osilodrostat or mifepristone.
--Use of the adrenolytic mitotane at any point, due to its prolonged half-life.
--Use of medications that block ACTH release within the past two weeks - cabergoline, octreotide (subcutaneous), pasireotide (subcutaneous), megestrol acetate, other synthetic glucocorticoids (except for topical or inhaled agents)
-Use of intramuscular long-acting forms of octreotide or pasireotide within the past 4 months.
--Treatment of diabetes insipidus.
--Use of oral, injectable, or inhaled glucocorticoids (unless intermittent, for symptomatic asthma) within the last year. Use of topical non-hydrocortisone containing potent glucocorticoids on more than 36 square inches in the last six months.
--Hemoglobin A1c >= 6.5% on screening labs.
Principal Investigator
Referral Contact
For more information: