Cushing's DiseasePhase 2NCT04339751
Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing s Disease
A Phase 2 study testing Vorinostat in people with Cushing's Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: Cushing s disease is caused by excess ACTH hormone release by a benign tumor of the pituitary gland. It can lead to decreased quality of life and early death. The current best treatment for Cushing s disease is surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cushing's Disease
- What is being tested?
- Vorinostat
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Apr 2025to 11 Apr 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Adult patients (18 years and older)
- Confirmed biochemical diagnosis of Cushing s disease (primary or recurrent) as evidenced by increased 24-hour urine free cortisol (UFC), normal or increased morning plasma Adrenocorticotropic Hormone (ACTH), and pituitary origin of excess ACTH.
- Surgical candidate for resection of ACTH producing pituitary adenoma
- Enrolled in 03-N-0164, Evaluation of Neurosurgical Disorders.
- Able to provide written informed consent at the time of study enrollment.
- Participants who are physically able to become pregnant must use an effective form of birth control from 14 days prior to enrollment through 6 months following the last dose of vorinostat. Participants who are able to father a child must use an effective form of birth control from Day 0 through 3 months following the last dose of vorinostat.
Who cannot join
- Patients who have been previously treated with vorinostat.
- Patients who have received sellar radiation.
- Significant medical illnesses that in the investigator s opinion cannot be adequately controlled or would compromise the patient s ability to tolerate this vorinostat.
- Any history of cancer, unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
- History of thromboembolic disorder or deep vein thrombosis
- Presence of abnormal hematological and biochemical parameters, (such as anemia or thrombocytopenia) as defined as:
Show all 22Show fewer
- Neutrophil count < 1.5 K//micro L
- Hemoglobin < 8.0 g/dL.
- Hematocrit < 0.75x LLN (lower limit of normal)
- RBC count < 0.75x LLN
- Platelet count < 100 x 10^3 cells/micro L.
- Prothrombin time-international normalized ratio (PT-INR) > 1.5x ULN or Activated partial thromboplastin time (aPTT) > 1.5x ULN, with the exception of patients on prophylactic anticoagulation therapy
- Serum bilirubin level > 1.5x ULN.
- Active infection being currently treated with systemic antibiotics.
- Serious concurrent medical illness including renal failure (creatinine >3.0x - 6.0x ULN) liver failure (ALT/AST >5.0x - 20.0x ULN) or severe cardio-respiratory disease.
- Pregnancy or lactation.
- Presence of any disease that will obscure toxicity or dangerously alter drug metabolism (such as uncontrolled diabetes or bleeding disorders)
- Currently receiving other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat, such as valproate.
- Currently taking another HDACi, such as valproate.
- Currently taking coumadin or its derivative anticoagulants.
- Currently taking any other medication to reduce cortisol or ACTH levels
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: The Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing's Disease
Background:
Cushing s disease is caused by excess ACTH hormone release by a benign tumor of the pituitary gland. It can lead to decreased quality of life and early death. The current best treatment for Cushing s disease is surgery. If surgery does not work or if the tumor returns, there are no more good treatment options. Vorinostat, which is approved to treat a type of lymphoma, might be a treatment option.
Read more
Objective:
To test vorinostat to see if it can kill tumor cells and change the number of hormones released in people with Cushing s disease.
Eligibility:
People ages 18 and older who have Cushing s disease and are scheduled for surgery under protocol 03-N-0164 to remove a tumor in their pituitary gland
Design:
Participants will be screened under protocol 03-N-0164.
Participants will stay in the hospital for 8 days before their surgery.
On the first day, participants will have a physical exam and blood tests. They will have their urine collected for testing all day. They will have an ECG: For this, small metal disks or sticky electrode pads will be placed on their chest to record heart activity.
For the next 7 days, participants will have blood tests and all-day urine collection. They will drink at least 2 liters of fluid per day. They will take the study drug by mouth each morning.
On the eighth day, participants will have their surgery. Leftover tissue will be collected for research.
On the day they are discharged from the hospital, participants will have a physical exam and blood tests.
Read the detailed description
Study Description
This is a single center, prospective pilot study of effectiveness of vorinostat to reduce midnight ACTH levels in patients with Cushing s Disease. Surgery for resection of ACTH producing pituitary adenoma will be offered at the NIH under another protocol (03-N-0164) as part of standard clinical care. Eligible subjects will be admitted to the Clinical Center for one week prior to surgery, during which time oral vorinostat will be administered daily.
Objectives
Cushing s disease is caused by excess ACTH hormone release by a benign tumor of the pituitary gland. The resulting increase in cortisol levels caused by increased ACTH causes a severe condition that leads to decreased quality of life and early death. The current best first treatment for Cushing s disease is surgery. However, if surgery is unsuccessful or if the tumor returns, there are no good treatment options for patients. In laboratory studies, we discovered that a previously FDA approved oral medication Vorinostat was able to kill tumors cells and reduce ACTH secretion. We want to test whether this drug can be used in patients with Cushing s disease to reduce ACTH levels.
Primary Objective: to determine whether vorinostat reduces midnight plasma ACTH level
Secondary Objectives: to evaluate the effect of vorinostat on urine cortisol levels
Endpoints
Primary Endpoint: midnight plasma ACTH level on the last day of drug administration. Secondary Endpoints: serum cortisol change during drug administration.
- Conditions
- Cushing's Disease
- Being tested
- Vorinostat
- Keywords
- SAHA, CD
- Medical subject headings
- Pituitary ACTH Hypersecretion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VorinostatDrug
Administration of Vorinostat
| Study group | Role | What they receive |
|---|---|---|
| single center, prospective pilot study | Experimental | effectiveness of vorinostat to reduce midnight ACTH levels in patients with Cushing s Disease Receives: Drug: Vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Midnight Plasma ACTH
Relative change in midnight plasma ACTH. Dichotomized relative change using 20% as a cutoff (which is considered as clinical important): relative change >20% for reduction and relative change <=20% for no change).
Measured: Day -1, Day 0-1, Day 2, Day 4-6, Discharge
Secondary outcomes (1)
Urinary Free Cortisol
Relative change in 24-hour urinary free cortisol during 7 day administration of Vorinostat
Measured: Day -1, Day 0-1, Day 2, Day 4-6, Discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2020
- Study start11 Apr 2025
- Primary completion11 Apr 2025
- Study completion11 Apr 2025
Why it stopped: Lack of enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cushing's DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Prashant Chittiboina, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04339751
- Sponsor's protocol ID
- 200019
- Other IDs
- 20-N-0019
- Status last verified
- Apr 2025
- First submitted
- 8 Apr 2020
- Last updated
- 15 Apr 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: We do plan to share IPD. we will share all IPD that results in a publication on a public repository, as required by most journals. the data will be de-identified and anonymized.
Publications
Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, Fava GA, Findling JW, Gaillard RC, Grossman AB, Kola B, Lacroix A, Mancini T, Mantero F, Newell-Price J, Nieman LK, Sonino N, Vance ML, Giustina A, Boscaro M. Diagnosis and complications of Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab. 2003 Dec;88(12):5593-602. doi: 10.1210/jc.2003-030871.
PubMed 14671138Cushing H. The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). 1932. Obes Res. 1994 Sep;2(5):486-508. doi: 10.1002/j.1550-8528.1994.tb00097.x. No abstract available.
PubMed 16353601Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing's syndrome. Lancet. 2006 May 13;367(9522):1605-17. doi: 10.1016/S0140-6736(06)68699-6.
PubMed 16698415
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing's Disease
- ClinicalTrials.gov ID
- NCT04339751
- Acronym / sponsor ID
- 200019
- Conditions
- Cushing's Disease
- Keywords
- SAHA, CD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of enrollment.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 11 Apr 2025 (actual)
- Primary completion
- 11 Apr 2025 (actual)
- Study completion
- 11 Apr 2025 (actual)
- First posted
- 9 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Cushing s disease is caused by excess ACTH hormone release by a benign tumor of the pituitary gland. It can lead to decreased quality of life and early death. The current best treatment for Cushing s disease is surgery. If surgery does not work or if the tumor returns, there are no more good treatment options. Vorinostat, which is approved to treat a type of lymphoma, might be a treatment option.
Objective:
To test vorinostat to see if it can kill tumor cells and change the number of hormones released in people with Cushing s disease.
Eligibility:
People ages 18 and older who have Cushing s disease and are scheduled for surgery under protocol 03-N-0164 to remove a tumor in their pituitary gland
Design:
Participants will be screened under protocol 03-N-0164.
Participants will stay in the hospital for 8 days before their surgery.
On the first day, participants will have a physical exam and blood tests. They will have their urine collected for testing all day. They will have an ECG: For this, small metal disks or sticky electrode pads will be placed on their chest to record heart activity.
For the next 7 days, participants will have blood tests and all-day urine collection. They will drink at least 2 liters of fluid per day. They will take the study drug by mouth each morning.
On the eighth day, participants will have their surgery. Leftover tissue will be collected for research.
On the day they are discharged from the hospital, participants will have a physical exam and blood tests.
Detailed description
Study Description
This is a single center, prospective pilot study of effectiveness of vorinostat to reduce midnight ACTH levels in patients with Cushing s Disease. Surgery for resection of ACTH producing pituitary adenoma will be offered at the NIH under another protocol (03-N-0164) as part of standard clinical care. Eligible subjects will be admitted to the Clinical Center for one week prior to surgery, during which time oral vorinostat will be administered daily.
Objectives
Cushing s disease is caused by excess ACTH hormone release by a benign tumor of the pituitary gland. The resulting increase in cortisol levels caused by increased ACTH causes a severe condition that leads to decreased quality of life and early death. The current best first treatment for Cushing s disease is surgery. However, if surgery is unsuccessful or if the tumor returns, there are no good treatment options for patients. In laboratory studies, we discovered that a previously FDA approved oral medication Vorinostat was able to kill tumors cells and reduce ACTH secretion. We want to test whether this drug can be used in patients with Cushing s disease to reduce ACTH levels.
Primary Objective: to determine whether vorinostat reduces midnight plasma ACTH level
Secondary Objectives: to evaluate the effect of vorinostat on urine cortisol levels
Endpoints
Primary Endpoint: midnight plasma ACTH level on the last day of drug administration. Secondary Endpoints: serum cortisol change during drug administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single center, prospective pilot study | Experimental | Drug: Vorinostateffectiveness of vorinostat to reduce midnight ACTH levels in patients with Cushing s Disease |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Adult patients (18 years and older)
- Confirmed biochemical diagnosis of Cushing s disease (primary or recurrent) as evidenced by increased 24-hour urine free cortisol (UFC), normal or increased morning plasma Adrenocorticotropic Hormone (ACTH), and pituitary origin of excess ACTH.
- Surgical candidate for resection of ACTH producing pituitary adenoma
- Enrolled in 03-N-0164, Evaluation of Neurosurgical Disorders.
Key exclusion criteria (22 listed)
- Patients who have been previously treated with vorinostat.
- Patients who have received sellar radiation.
- Significant medical illnesses that in the investigator s opinion cannot be adequately controlled or would compromise the patient s ability to tolerate this vorinostat.
- Any history of cancer, unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
- History of thromboembolic disorder or deep vein thrombosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VorinostatAdministration of Vorinostat | Drug | single center, prospective pilot study |
Primary outcome
Midnight Plasma ACTH
Time frame: Day -1, Day 0-1, Day 2, Day 4-6, Discharge
Relative change in midnight plasma ACTH. Dichotomized relative change using 20% as a cutoff (which is considered as clinical important): relative change >20% for reduction and relative change <=20% for no change).
1 secondary outcome
Urinary Free Cortisol
Time frame: Day -1, Day 0-1, Day 2, Day 4-6, Discharge
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2025.
- Background: PubMed 14671138Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, Fava GA, Findling JW, Gaillard RC, Grossman AB, Kola B, Lacroix A, Mancini T, Mantero F, Newell-Price J, Nieman LK, Sonino N, Vance ML, Giustina A, Boscaro M. Diagnosis and complications of Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab. 2003 Dec;88(12):5593-602. doi: 10.1210/jc.2003-030871.
- Background: PubMed 16353601Cushing H. The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). 1932. Obes Res. 1994 Sep;2(5):486-508. doi: 10.1002/j.1550-8528.1994.tb00097.x. No abstract available.
- Background: PubMed 16698415Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing's syndrome. Lancet. 2006 May 13;367(9522):1605-17. doi: 10.1016/S0140-6736(06)68699-6.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. We do plan to share IPD. we will share all IPD that results in a publication on a public repository, as required by most journals. the data will be de-identified and anonymized.
Related trials for Cushing's Disease
RecruitingObservational study
Adrenal Diseases in the Population of Modena: A Clinical-Epidemiological Database of Patients Referred to the Adrenal Disorders Outpatient Clinic of the Clinical Unit of Endocrinology at the Modena University Hospital (AOU Modena)
Cushing s Syndrome, Cushing Disease
Active, not recruitingPhase 2
Extension Study to Evaluate the Safety of Long-Term Use of Relacorilant in Patients With Cushing Syndrome
Cushing Syndrome
RecruitingPhase 1/2
Diagnostic Value of CXCR4-targeted PET/CT in ACTH-dependent and Independent Cushing's Syndrome
Cushing s Syndrome
RecruitingObservational study
Long-Term Follow-Up of Survivors of Pediatric Cushing Disease
Cushing Disease
RecruitingPhase 4
Osilodrostat in Patients With Hypertension Caused by Hypercortisolaemia Due to Cushing's Syndrome
Hypertension, Hypercortisolemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Prashant Chittiboina, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vorinostat in people with Cushing's Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Midnight Plasma ACTH (time frame: Day -1, Day 0-1, Day 2, Day 4-6, Discharge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04339751, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2025.