An observational study in Endogenous Cushing Syndrome, Adrenal Insufficiency and Hypercortisolism, sponsored by University of Michigan. Recruiting at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-09-09.
Sponsored by University of Michigan · Observational
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.
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.
136 studies on the registry are indexed under Adrenal Insufficiency; 27 are open to participants now.
This study's planned enrollment of 12 is below the median of 85 across 59 observational studies indexed under Adrenal Insufficiency.
Browse Adrenal Insufficiency studies →University of Michigan is the lead sponsor of 1,506 studies on the registry; 192 are open to participants now.
Of its 169 completed or terminated interventional studies of FDA-regulated products, 133 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Patients receiving care at the University of Michigan.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants with Cushing syndrome consented to participate in block-and-replace osilodrostat therapy.
Drug: Osilodrostat
Add methylprednisolone to osilodrostat therapy after first dose and continue during osilodrostat titration.
Also known as: Isturisa
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
Time frame: Through phase 1, approximately 24 weeks
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.
Time frame: 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
Time frame: Up to end of phase 2 (approximately 48 weeks)
Frequency of cortisol withdrawal symptoms
Based on patient-reported outcomes
Time frame: Up to end of phase 2 (approximately 48 weeks)
Change in weight
Based on clinic measurements
Time frame: Baseline, end of phase 2 (approximately 48 weeks)
Change in diastolic blood pressure
Based on clinic measurements
Time frame: Baseline, end of phase 2 (approximately 48 weeks)
Change in systolic blood pressure
Based on clinic measurements
Time frame: Baseline, end of phase 2 (approximately 48 weeks)
Mean change in HgbA1c for participant with HgbA1c > 6.4% at entry.
Based on clinic measurements
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: Up to end of study, approximately 48 weeks
Ease of titration
Investigators' judgment (1-5 scale)
Time frame: Up to end of phase 1 (approximately 48 weeks)
Plan to share: No
No publications or documents are linked to this record.
Started Jul 2024 (actual). Primary completion is estimated for Oct 2027, 39 months after the start.
Of 27 observational studies under Adrenal Insufficiency, half reached primary completion within 31 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 98. This study's planned 39 months is above that.
How these figures are worked out, and which studies are left out of them.
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