Desmopressin Test for Cushing Syndrome

Overseen by Lynnette K Nieman, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Must not be taking: Glucocorticoids, Vasopressors, CYP3A4 inducers, others

Disqualifiers: Pregnancy, Heart disease, Hypertension, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

Yes, you may need to stop certain medications. The trial excludes participants who are currently using specific drugs like desmopressin, systemic glucocorticoids, vasopressors, and certain other medications that affect hormone levels or interact with desmopressin. It's important to discuss your current medications with the trial team to see if any changes are needed.

What data supports the effectiveness of the drug Desmopressin in diagnosing Cushing's syndrome?

Research suggests that the desmopressin test can help in diagnosing Cushing's disease by distinguishing it from similar conditions and monitoring cyclical patterns in the disease. ^{1 2 3 4 5}

Is the desmopressin test safe for humans?

The research articles do not provide specific safety data for desmopressin (DDAVP) in humans, focusing instead on its diagnostic use in Cushing's syndrome. ^{1 2 3 4 6}

How does the drug desmopressin differ from other treatments for Cushing Syndrome?

Desmopressin is unique because it is a synthetic drug that targets vasopressin receptors, specifically used to help diagnose and manage Cushing's disease by stimulating ACTH (a hormone that stimulates cortisol production) release. Unlike other treatments, it is particularly useful in distinguishing between Cushing's disease and similar conditions, and it can be used when other diagnostic agents like corticotropic-releasing hormone are unavailable. ^{1 2 4 7 8}

Research Team

Lynnette K Nieman, MD

Principal Investigator

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

Eligibility Criteria

This trial is for adults aged 18 to 70 who may have Cushing syndrome (CS), particularly Cushing disease (CD) or ectopic ACTH syndrome (EAS). Healthy volunteers are also needed. Participants with CS will undergo three DesmoSTs, and healthy ones will have four tests spaced days apart.

Inclusion Criteria

Healthy volunteers: In good general health as evidenced by medical history and physical examination, In a stable state of health without ongoing acute/temporary illness per the clinical judgement of the investigator

I am between 18 and 70 years old.

Agreement to adhere to Lifestyle Considerations throughout the study

Exclusion Criteria

I have not used strong CYP3A4 inducers, St John's wort, or nafcillin in the last 14 days.

Inability to comply with all study procedures and visits

Known allergy/hypersensitivity to desmopressin

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Desmopressin Stimulation Tests

Participants with CS will undergo 3 DesmoSTs at least 48 hours apart, and healthy volunteers will have 4 DesmoSTs 2 to 14 days apart.

2-4 weeks

3-4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after each DesmoST, with follow-up visits 3 to 5 days after each test.

3-5 days after each test

3-4 visits (phone or in-person)

Treatment Details

Interventions

• Desmopressin (Hormone Therapy)
• Dexamethasone (Corticosteroid)

Trial Overview The study aims to improve the accuracy of the desmopressin stimulation test in diagnosing ACTH-dependent CS. It involves taking dexamethasone before one of the tests and measuring blood cortisol levels multiple times after administering desmopressin.

Participant Groups

Group I: Desmopressin 10 mcg Ad-lib fluid Experimental Treatment 1 Intervention

Desmopressin 10 mcg Ad-lib fluidHealthy volunteers only

Group II: Desmopressin 10 mcg NPO Active Control 1 Intervention

Desmopressin 10 mcg

Group III: Desmopressin NPO 4 mcg Active Control 1 Intervention

Desmopressin 4 mcg

Group IV: Dexmopressin 10 mcg NPO + Dexamethasone Active Control 2 Interventions

Desmopressin 10 mcgDexamethasone 1 mg pretreatment

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

2,513

Recruited

4,366,000+

Findings from Research

The desmopressin (DDAVP) stimulation test showed a high sensitivity of 87% for diagnosing ACTH-dependent Cushing's syndrome, while the high dose dexamethasone suppression test (HDDST) had a sensitivity of 79%.

Combining the DDAVP stimulation test and HDDST resulted in a 100% diagnostic accordance rate when both tests provided consistent results, indicating that using both tests together enhances diagnostic accuracy for Cushing's disease and ectopic ACTH syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Value of desmopressin stimulation test and high dose dexamethasone suppression testin the etiologic diagnosis of ACTH dependent Cushing's syndrome]. Zhang, W., Yu, Y., Tan, H., et al.[2018]

The desmopressin (DDAVP) test proved to be a valuable tool in diagnosing cyclical Cushing's disease (CCS), as it consistently indicated a positive response even when typical symptoms of Cushing's syndrome were not present.

After identifying a pituitary adenoma as the source of ACTH production through MRI and confirming the diagnosis with the DDAVP test, the patient's symptoms resolved following surgery, demonstrating the test's effectiveness in guiding treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Desmopressin test in the diagnosis and follow-up of cyclical Cushing's disease. Leal-Cerro, A., Martín-Rodríguez, JF., Ibáñez-Costa, A., et al.[2018]

In a study of 47 patients with Cushing's disease, those with USP8 mutations showed a significantly greater response to the desmopressin (DDAVP) test, indicating that these mutations may enhance ACTH and cortisol responsiveness.

The results suggest that the DDAVP test can be a useful tool for predicting the presence of USP8 mutations in Cushing's disease, as responsiveness to DDAVP was linked to higher expression levels of the AVPR1B receptor associated with these mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responsiveness to DDAVP in Cushing's disease is associated with USP8 mutations through enhancing AVPR1B promoter activity. Shichi, H., Fukuoka, H., Kanzawa, M., et al.[2022]

In a study of 124 patients suspected of having Cushing's syndrome, the desmopressin (DDAVP) test demonstrated high diagnostic accuracy for Cushing's disease, with a sensitivity of 90.8% and specificity of 94.6%.

An ACTH peak of 71.8 pg/ml after DDAVP administration was particularly effective, indicating that the DDAVP test is a superior method compared to other clinical tools for diagnosing Cushing's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the DDAVP test in the diagnosis of Cushing's Disease. Rollin, GA., Costenaro, F., Gerchman, F., et al.[2015]

The desmopressin (DDAVP) test effectively distinguishes Cushing's disease from normal subjects and other conditions, as evidenced by a significant increase in plasma ACTH levels in all 10 patients with Cushing's disease compared to lower levels in 19 other patients with different conditions.

DDAVP stimulates ACTH release from corticotropic adenoma cells via V1b vasopressin receptors, indicating a specific mechanism of action that supports its diagnostic utility in identifying ACTH-dependent Cushing's syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Desmopressin stimulation test for diagnosis of ACTH-dependent Cushing's syndrome. Sakai, Y., Horiba, N., Tozawa, F., et al.[2019]

Desmopressin specifically stimulates ACTH expression and release in corticotropinoma cells due to high levels of AVPR1b receptor expression, making it a reliable test for diagnosing and monitoring Cushing disease.

The study suggests that AVPR1b is the key receptor mediating desmopressin's effects, indicating potential for AVPR1b antagonists to be developed as new treatments for Cushing disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cellular and molecular basis for the selective desmopressin-induced ACTH release in Cushing disease patients: key role of AVPR1b receptor and potential therapeutic implications. Luque, RM., Ibáñez-Costa, A., López-Sánchez, LM., et al.[2015]

References

1. China pubmed.ncbi.nlm.nih.gov

[Value of desmopressin stimulation test and high dose dexamethasone suppression testin the etiologic diagnosis of ACTH dependent Cushing's syndrome]. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Use of the desmopressin test in the differential diagnosis of pseudo-Cushing state from Cushing's disease. [2015]

3. Spain pubmed.ncbi.nlm.nih.gov

Desmopressin test in the diagnosis and follow-up of cyclical Cushing's disease. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Responsiveness to DDAVP in Cushing's disease is associated with USP8 mutations through enhancing AVPR1B promoter activity. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Evaluation of the DDAVP test in the diagnosis of Cushing's Disease. [2015]

6. Japan pubmed.ncbi.nlm.nih.gov

Desmopressin stimulation test for diagnosis of ACTH-dependent Cushing's syndrome. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

A cellular and molecular basis for the selective desmopressin-induced ACTH release in Cushing disease patients: key role of AVPR1b receptor and potential therapeutic implications. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Bilateral inferior petrosal sinus sampling using desmopressin or corticotropic-releasing hormone: a single-center experience. [2021]