Desmopressin Test for Cushing Syndrome

Overseen By Lynnette K Nieman, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve a test for diagnosing Cushing syndrome, a condition where the body produces excess cortisol. The trial will evaluate how effectively the desmopressin stimulation test (DesmoST) identifies individuals with specific types of Cushing syndrome. Participants will receive desmopressin, and some will also take dexamethasone to assess its impact on test results. Suitable candidates include those diagnosed with or suspecting Cushing syndrome, particularly if they experience symptoms like unexplained weight gain or frequent mood changes. Healthy volunteers are also needed for comparison. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that desmopressin is generally safe for humans in similar tests. Although specific safety data for desmopressin in humans is limited, studies suggest it is a safe and effective choice compared to other test agents. People with Cushing's syndrome might have a higher risk of blood clotting, so extra care is necessary.

There is no specific safety data for the combination of desmopressin and dexamethasone. However, desmopressin is often used safely in similar tests, and dexamethasone is a well-known drug used in various tests for Cushing's syndrome. This trial is in Phase 2, indicating that the treatment has already passed initial safety checks. Further research is needed to fully understand its safety in this setting. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Desmopressin test for Cushing Syndrome because it offers a unique way to potentially diagnose the condition. Unlike standard treatments that focus on reducing cortisol production or blocking its effects, this approach uses Desmopressin to examine how the body responds to hormone stimulation, which could provide new insights into diagnosing Cushing Syndrome. By exploring different dosages and combinations, such as Desmopressin with Dexamethasone, researchers hope to fine-tune this method, potentially leading to more accurate and earlier diagnosis of Cushing Syndrome, which is crucial for effective management.

What evidence suggests that the Desmopressin Test is effective for diagnosing Cushing Syndrome?

Research has shown that the desmopressin test can help differentiate between Cushing disease (CD) and other conditions causing high cortisol levels. One study found that it corrected diagnoses in cases where other tests failed. In this trial, participants may receive Desmopressin alone or with Dexamethasone. Desmopressin is safe and mimics CRH, a hormone used to diagnose ACTH-related conditions. When combined with Dexamethasone, it can enhance diagnostic accuracy. This combination has shown promise in predicting outcomes for patients who have undergone surgery for Cushing's disease. ^{4 5 6 7 8}

Who Is on the Research Team?

Lynnette K Nieman, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

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

Agreement to adhere to Lifestyle Considerations throughout the study

Evidence of acceptable laboratory testing results within four weeks of the first test day: Hematocrit at entry >=33 %, Plasma sodium 136-145 mmol/L (unless taking a drug that can cause hyponatremia), eGFR >=60 ml/min/1.73 sq.m based on serum creatinine

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Desmopressin
• Dexamethasone

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

The desmopressin (DDAVP) test, when interpreted using specific cortisol and ACTH levels, effectively distinguishes Cushing's disease (CD) from pseudo-Cushing states (PC), achieving a sensitivity of 90.3% and specificity of 91.5%.

This method is particularly useful for identifying CD in patients with mild hypercortisolism, demonstrating high effectiveness even with moderate cortisol levels after dexamethasone suppression and at midnight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of the desmopressin test in the differential diagnosis of pseudo-Cushing state from Cushing's disease. Tirabassi, G., Faloia, E., Papa, R., et al.[2015]

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) 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]

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]

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]

In a study of 20 patients using desmopressin (DDAVP) for bilateral inferior petrosal sinus sampling (BIPSS), the technique was safe with no complications, and it achieved a high sensitivity of 94.5% for diagnosing Cushing disease.

The diagnostic results obtained with DDAVP were comparable to those achieved with corticotropic-releasing hormone (CRH), indicating that DDAVP can be an effective alternative in the absence of CRH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral inferior petrosal sinus sampling using desmopressin or corticotropic-releasing hormone: a single-center experience. Deipolyi, AR., Alexander, B., Rho, J., et al.[2021]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10861662/

Accuracy of the 10 μg desmopressin test for differential ... We evaluated the accuracy of the 10 μg desmopressin test in differentiating Cushing disease (CD) from non-neoplastic hypercortisolism (NNH) and ectopic ACTH ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06635629

Study Details | NCT06635629 | Desmopressin Stimulation ... The goal of this study is to improve the diagnostic accuracy of the Desmopressin stimulation test (DesmoST) for three indications.

3. academic.oup.com academic.oup.com/jcem/article/101/12/4878/2765072

The Desmopressin Test Predicts Better Than Basal Cortisol ... The Desmopressin Test Predicts Better Than Basal Cortisol the Long-Term Surgical Outcome of Cushing's Disease Free ; Objective: The utility of ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0003426624007613

Desmopressin is a safe and effective secretagogue to ... Desmopressin is a good substitute for CRH, correcting diagnosis compared to baseline BIPSS in 12% of cases.

5. ec.bioscientifica.com ec.bioscientifica.com/view/journals/ec/6/8/EC-17-0292.xml

Usefulness of desmopressin testing to predict relapse during ... We tested 56 patients with Cushing's disease in remission after transsphenoidal surgery with desmopressin for up to 20 years after surgery.

6. jnis.bmj.com jnis.bmj.com/content/caution-during-use-ddavp-ipss

Caution during use of DDAVP in IPSS Desmopressin is also a potent haemostatic agent and that patients with Cushing's syndrome are at increased risk for thromboembolic events.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10741245/

Cushing's Disease: Long-Term Effectiveness and Safety of ... This study supports and strengthens the role of osilodrostat as an effective long-term medical treatment in patients with CD.

8. withpower.com withpower.com/trial/phase-2-syndrome-10-2024-93686

Desmopressin Test for Cushing Syndrome Is the desmopressin test safe for humans? The research articles do not provide specific safety data for desmopressin (DDAVP) in humans, focusing instead on ...