Osilodrostat for Autonomous Cortisol Secretion

Overseen By Tony Keyes

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Johns Hopkins University

Must not be taking: Glucocorticoids, Ketoconazole, Metyrapone, others

Disqualifiers: Cushing's syndrome, Pregnancy, 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: 3

Duration: 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how the drug osilodrostat (Isturisa) can assist individuals with mild autonomous cortisol secretion (MACS), a condition where the body produces excess cortisol, a stress hormone. Researchers aim to determine if this drug can improve body composition, reduce heart and metabolism risks, and enhance overall health. The trial includes tests such as body scans and blood pressure checks before and after treatment. Participants must have MACS, confirmed by a special test indicating cortisol levels and a scan revealing an adrenal gland issue. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment can benefit more patients.

What is the safety track record for this treatment?

Research has shown that osilodrostat (Isturisa) is generally well-tolerated. In studies, some patients experienced a drop in cortisol levels without major side effects. However, reports of rib and spine fractures exist, possibly linked to pre-existing bone issues like osteoporosis rather than the drug itself. This indicates that not everyone taking osilodrostat will experience fractures. The FDA has approved the treatment for other conditions, suggesting a known safety record. Overall, while some side effects are possible, current research indicates that osilodrostat appears safe for many people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Osilodrostat (Isturisa) is unique because it specifically targets and inhibits the enzyme 11β-hydroxylase, a key player in cortisol production. Unlike traditional treatments like ketoconazole or metyrapone, which can affect multiple pathways and have broader side effects, Osilodrostat provides a more targeted approach. Researchers are excited about its potential to more precisely manage cortisol levels, which could lead to better control of metabolic outcomes and body composition in patients with Mild Autonomous Cortisol Secretion (MACS).

What is the effectiveness track record for osilodrostat in treating mild autonomous cortisol secretion?

Research has shown that osilodrostat (Isturisa), which participants in this trial will receive, effectively lowers cortisol levels. In one study, all patients experienced a significant drop in cortisol after just two weeks of treatment. This is important because high cortisol can cause weight gain and other health issues. Another study found that taking osilodrostat once a day reduced cortisol levels, potentially improving body weight and overall health. These findings suggest that osilodrostat can effectively manage symptoms in people with mild autonomous cortisol secretion (MACS). ^{1 3 5 6 7}

Who Is on the Research Team?

Amir Hamrahian, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for individuals with mild autonomous cortisol secretion (MACS), which can lead to excess cortisol production. Participants should be diagnosed with MACS and are expected to undergo various assessments like DEXA scans, lab tests, and blood pressure measurements.

Inclusion Criteria

My test shows mild cortisol secretion after a specific suppression test.

I can understand and agree to the study's procedures and risks.

I am 18 years old or older.

Exclusion Criteria

I have been diagnosed with Cushing's syndrome.

I have taken steroids or medications affecting cortisol recently.

I have severe liver problems or kidney failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including DEXA scans, bone mineral density measurements, blood pressure evaluation, anthropometric measurements, and laboratory testing

1-2 weeks

Treatment

Participants receive osilodrostat (Isturisa) and are monitored for changes in body composition, metabolic markers, and cardiometabolic risk factors

2 years

Every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Osilodrostat (Isturisa)

Trial Overview The study is testing the effects of a medication called Osilodrostat (Isturisa) on body composition and cardiometabolic risk factors in patients with MACS. It aims to see if this treatment can improve metabolic outcomes and reduce health risks associated with excess cortisol.

How Is the Trial Designed?

Group I: Isturisa Treatment Arm Experimental Treatment 1 Intervention

Participants diagnosed with Mild Autonomous Cortisol Secretion (MACS) will receive Osilodrostat (Isturisa) as an investigational treatment. The intervention aims to evaluate cortisol reduction, metabolic outcomes, and changes in body composition, including DEXA-based assessments.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07247058

Isturisa Treatment in Mild Autonomous Cortisol Secretion ... This study aims to evaluate changes in body composition and cardiometabolic risk factors in patients with mild autonomous cortisol secretion ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07104812

Impact of 1 mg Osilodrostat Therapy on Mild Autonomous ... Suspected false positive post-dexamethasone cortisol results due to increased metabolism, poor absorption, or noncompliance with dexamethasone.

3. mayo.edu mayo.edu/research/clinical-trials/cls-20590378?p=1

Impact Of 1 Mg Osilodrostat Therapy On Mild Autonomous ... In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11915091/

Osilodrostat Treatment for Adrenal and Ectopic Cushing ... All patients achieved cortisol control with osilodrostat 4 to 40 mg/day; in 6 patients, UFC and/or serum cortisol significantly decreased after 2 weeks of ...

5. academic.oup.com academic.oup.com/jcem/article/110/12/3525/8104034

Chronotherapy With Once-Daily Osilodrostat Improves ... Compared to the standard twice-daily regimen, once-daily dosing resulted in significantly reduced late afternoon to early morning cortisol exposure (AUC16:00-08 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12112102/

Osilodrostat Safety Profile: Findings from Real-World Data ... Rib and spinal fractures in patients treated with osilodrostat are likely due to a combination of pre-existing osteoporosis and impaired bone ...

7. academic.oup.com academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgaf633/8328378?searchresult=1

Real-world osilodrostat effectiveness and safety in non ... Osilodrostat was initiated and titrated based on investigator judgment. Cortisol decreased by W4, remaining stable thereafter. 23/52 patients ( ...