Endogenous Cushing SyndromeNCT06430528
A Block-and-Replace Therapy With Osilodrostat and Concomitant Glucocorticoid Replacement
An observational study of Endogenous Cushing Syndrome and Adrenal Insufficiency, run by University of Michigan at 1 site in United States.
Trial summary
The major goal of this study is to determine the incidence of adrenal insufficiency in patients with endogenous Cushing syndrome receiving osilodrostat treatment combined with a replacement of glucocorticoid (block-and-replace approach). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Endogenous Cushing Syndrome, Adrenal Insufficiency, Hypercortisolism
- What is being tested?
- Osilodrostat
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jul 2024to Jan 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients receiving care at the University of Michigan.
Who may be able to join
- Endogenous Cushing syndrome, either following surgery or not candidates for surgery
- Under consideration to receive osilodrostat as part of their clinical care
- Able to provide informed consent.
Who cannot join
- Treatment with other investigational drugs within 30 days or five half-lives (whichever is longer).
- A history of hypersensitivity to osilodrostat or therapies of a similar chemical class.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Eyad Alsafadi, 734-647-5661, alsafade@med.umich.edu
Thaira Blanco Varela, 734-647-5661, tbv@med.umich.edu
About this study
The major goal of this study is to determine the incidence of adrenal insufficiency in patients with endogenous Cushing syndrome receiving osilodrostat treatment combined with a replacement of glucocorticoid (block-and-replace approach).
The investigators are also evaluating new biomarker steroids to reflect adequate osilodrostat dosing, the durability and safety, and clinical improvement during treatment.
Read the detailed description
Phase 1 (Titration):
Participants will provide written informed consent and receive the first dose of osilodrostat (1-2 mg) in the evening. The following morning, participants will add treatment with at least a physiologic replacement dose of methylprednisolone (4-6 mg/d based on body size in not more than 2 divided doses) and concurrently continue 1-2 mg BID of osilodrostat. Frequent communication is maintained with each participant, at least twice weekly for the first 3 months and weekly thereafter until target osilodrostat dose is reached. Study personnel will ask targeted questions related to the primary endpoint with parameters to notify the study physicians for early signs of adrenal insufficiency. Participants are instructed to double their methylprednisolone dose for intercurrent illness and for symptoms of cortisol deficiency or withdrawal that do not resolve with pausing osilodrostat dosing. Every 4-12 weeks, an AM cortisol, as well as a research sample for steroid profiling (including 11OHA4), is obtained prior to the first doses of methylprednisolone and osilodrostat. The osilodrostat dose is up-titrated as necessary to achieve an AM cortisol goal of <5 µg/dL. Once the AM cortisol is at goal, a late-night saliva cortisol (LNSC) and 24 h urine free cortisol (UFC) is obtained per standard of care. Osilodrostat titration is continued if necessary until the UFC is also at goal of <10 µg/24h. Once the AM cortisol and UFC are at goals (<5 µg/dL and <10 µg/24h, respectively), the primary endpoint measures are completed, and the participant enters Phase 2.
Phase 2 (Maintenance):
Once the participant reaches what the investigator considers the maintenance doses of osilodrostat and methylprednisolone, participants are followed for a total of 48 weeks from the first osilodrostat dose before being considered at the end of study. The AM serum cortisol, UFC, and LNSC are repeated at the end of the 48-week period and as clinically indicated throughout Phase 2, generally every 3-6 months.
- Being tested
- Osilodrostat
- Keywords
- Osilodrostat, Glucocorticoid, Methylprednisolone, Medrol
- Medical subject headings
- Adrenal Insufficiency, Cushing Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OsilodrostatDrug
Also called Isturisa
Add methylprednisolone to osilodrostat therapy after first dose and continue during osilodrostat titration.
| Study group | Role | What they receive |
|---|---|---|
| Observational cohort | Participants with Cushing syndrome consented to participate in block-and-replace osilodrostat therapy. Receives: Drug: Osilodrostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of participants who experience an adrenal insufficiency event during Phase 1 (titration phase)
based on evidence of hypotension (systolic BP <90 mmHg) and/or hypoglycemia (glucose <45 mg/dL) with antecedent symptoms (examples: anorexia, nausea, abdominal pain, orthostasis) and with a resolution of signs upon receiving rescue glucocorticoid therapy
Measured: Through phase 1, approximately 24 weeks
Secondary outcomes (11)
Correlation between AM cortisol and 11OHA4 measurements
compare biomarkers measured by mass spectrometry. This may be calculated Upon 12 participants completing phase 1 or at the end of the study, whichever comes first.
Measured: Up to end of study, approximately 48 weeks
Rate of adrenal insufficient episodes per patient per year
based on evidence of hypotension (systolic BP <90 mmHg) and/or hypoglycemia (glucose <45 mg/dL) with antecedent symptoms (examples: anorexia, nausea, abdominal pain, orthostasis) and with a resolution of signs upon receiving rescue glucocorticoid therapy
Measured: Up to end of phase 2 (approximately 48 weeks)
Frequency of cortisol withdrawal symptoms
Based on patient-reported outcomes
Measured: Up to end of phase 2 (approximately 48 weeks)
Change in weight
Based on clinic measurements
Measured: Baseline, end of phase 2 (approximately 48 weeks)
Change in diastolic blood pressure
Based on clinic measurements
Measured: Baseline, end of phase 2 (approximately 48 weeks)
Change in systolic blood pressure
Based on clinic measurements
Measured: Baseline, end of phase 2 (approximately 48 weeks)
Mean change in HgbA1c for participant with HgbA1c > 6.4% at entry.
Based on clinic measurements
Measured: Baseline, end of phase 2 (approximately 48 weeks)
Change in number of concomitant medications
Based on clinic notes, total number of medications used to treat Cushing syndrome comorbidities
Measured: Baseline, end of phase 2 (approximately 48 weeks)
Adrenal Insufficiency Assessment Questionnaire scores
Custom questionnaire for adrenal insufficiency- 4 Likert questions with scores ranging from 4-20. Higher scores indicate worse symptoms.
Measured: Up to end of study, approximately 48 weeks
RAND Short Form (SF)-36 scores
The 36-Item Short Form Health Survey (SF-36) is standard RAND form used clinically. It is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 with higher scores indicating a better Health-related Quality of Life.
Measured: Up to end of study, approximately 48 weeks
Ease of titration
Investigators' judgment (1-5 scale)
Measured: Up to end of phase 1 (approximately 48 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2024
- Study start19 Jul 2024
- Primary completionOct 2027 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endogenous Cushing SyndromeStudies of the same condition, open and under way.
- More trials run by University of MichiganThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- RECORDATI GROUP
- Responsible party
- Principal investigator, Richard J. Auchus, MD PhD, University of Michigan
- Investigators
- Richard Auchus, MD, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06430528
- Sponsor's protocol ID
- HUM00246263
- Status last verified
- Aug 2026
- First submitted
- 24 Apr 2024
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Block-and-Replace Therapy With Osilodrostat and Concomitant Glucocorticoid Replacement
- ClinicalTrials.gov ID
- NCT06430528
- Acronym / sponsor ID
- HUM00246263
- Keywords
- Osilodrostat, Glucocorticoid, Methylprednisolone, Medrol
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- RECORDATI GROUP
- Study start
- 19 Jul 2024 (actual)
- Primary completion
- Oct 2027 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 28 May 2024 (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.
The major goal of this study is to determine the incidence of adrenal insufficiency in patients with endogenous Cushing syndrome receiving osilodrostat treatment combined with a replacement of glucocorticoid (block-and-replace approach).
The investigators are also evaluating new biomarker steroids to reflect adequate osilodrostat dosing, the durability and safety, and clinical improvement during treatment.
Detailed description
Phase 1 (Titration):
Participants will provide written informed consent and receive the first dose of osilodrostat (1-2 mg) in the evening. The following morning, participants will add treatment with at least a physiologic replacement dose of methylprednisolone (4-6 mg/d based on body size in not more than 2 divided doses) and concurrently continue 1-2 mg BID of osilodrostat. Frequent communication is maintained with each participant, at least twice weekly for the first 3 months and weekly thereafter until target osilodrostat dose is reached. Study personnel will ask targeted questions related to the primary endpoint with parameters to notify the study physicians for early signs of adrenal insufficiency. Participants are instructed to double their methylprednisolone dose for intercurrent illness and for symptoms of cortisol deficiency or withdrawal that do not resolve with pausing osilodrostat dosing. Every 4-12 weeks, an AM cortisol, as well as a research sample for steroid profiling (including 11OHA4), is obtained prior to the first doses of methylprednisolone and osilodrostat. The osilodrostat dose is up-titrated as necessary to achieve an AM cortisol goal of <5 µg/dL. Once the AM cortisol is at goal, a late-night saliva cortisol (LNSC) and 24 h urine free cortisol (UFC) is obtained per standard of care. Osilodrostat titration is continued if necessary until the UFC is also at goal of <10 µg/24h. Once the AM cortisol and UFC are at goals (<5 µg/dL and <10 µg/24h, respectively), the primary endpoint measures are completed, and the participant enters Phase 2.
Phase 2 (Maintenance):
Once the participant reaches what the investigator considers the maintenance doses of osilodrostat and methylprednisolone, participants are followed for a total of 48 weeks from the first osilodrostat dose before being considered at the end of study. The AM serum cortisol, UFC, and LNSC are repeated at the end of the 48-week period and as clinically indicated throughout Phase 2, generally every 3-6 months.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Observational cohort | – | Drug: OsilodrostatParticipants with Cushing syndrome consented to participate in block-and-replace osilodrostat therapy. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients receiving care at the University of Michigan.
Key inclusion criteria (3 listed)
- Endogenous Cushing syndrome, either following surgery or not candidates for surgery
- Under consideration to receive osilodrostat as part of their clinical care
- Able to provide informed consent.
Key exclusion criteria (2 listed)
- Treatment with other investigational drugs within 30 days or five half-lives (whichever is longer).
- A history of hypersensitivity to osilodrostat or therapies of a similar chemical class.
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 |
|---|---|---|
| OsilodrostatAlso: IsturisaAdd methylprednisolone to osilodrostat therapy after first dose and continue during osilodrostat titration. | Drug | Observational cohort |
Primary outcome
Percent of participants who experience an adrenal insufficiency event during Phase 1 (titration phase)
Time frame: Through phase 1, approximately 24 weeks
based on evidence of hypotension (systolic BP <90 mmHg) and/or hypoglycemia (glucose <45 mg/dL) with antecedent symptoms (examples: anorexia, nausea, abdominal pain, orthostasis) and with a resolution of signs upon receiving rescue glucocorticoid therapy
11 secondary outcomes
Correlation between AM cortisol and 11OHA4 measurements
Time frame: Up to end of study, approximately 48 weeks
Rate of adrenal insufficient episodes per patient per year
Time frame: Up to end of phase 2 (approximately 48 weeks)
Frequency of cortisol withdrawal symptoms
Time frame: Up to end of phase 2 (approximately 48 weeks)
Change in weight
Time frame: Baseline, end of phase 2 (approximately 48 weeks)
Change in diastolic blood pressure
Time frame: Baseline, end of phase 2 (approximately 48 weeks)
Change in systolic blood pressure
Time frame: Baseline, end of phase 2 (approximately 48 weeks)
Mean change in HgbA1c for participant with HgbA1c > 6.4% at entry.
Time frame: Baseline, end of phase 2 (approximately 48 weeks)
Change in number of concomitant medications
Time frame: Baseline, end of phase 2 (approximately 48 weeks)
Adrenal Insufficiency Assessment Questionnaire scores
Time frame: Up to end of study, approximately 48 weeks
RAND Short Form (SF)-36 scores
Time frame: Up to end of study, approximately 48 weeks
Ease of titration
Time frame: Up to end of phase 1 (approximately 48 weeks)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
- Individual participant dataSharing planned: No
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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.
Richard Auchus, MD, PhD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Endogenous Cushing Syndrome and Adrenal Insufficiency, run by University of Michigan 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 3 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 9 Sep 2026. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Richard Auchus (734-764-7764, rauchus@med.umich.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent of participants who experience an adrenal insufficiency event during Phase 1 (titration phase) (time frame: Through phase 1, approximately 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Sep 2026.