ClinicalTrials.gg
Enrolling by invitationNCT07603466COSCA-ECDUpdated May 22, 2026

Combination Osilodrostat and Cabergoline in Cushing's Disease

A Phase 4 interventional study of osilodrostat and osilodrostat and cabergoline in Cushing Disease Due to Increased ACTH Secretion, sponsored by University of Basrah. Enrolling by invitation at 5 sites in Iraq. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-05-22.

Sponsored by University of Basrah · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
50
Allocation
Non-randomized
Ages
18 Years to 70 Years
Sex
All
01

Study summary

Cushing disease remains a challenging endocrine disorder in which persistent or recurrent hypercortisolism often requires medical therapy after surgery or when surgery is not feasible. Combination medical therapy has emerged as a rational strategy to improve biochemical control through complementary mechanisms while potentially reducing treatment escape and dose-related toxicity. Cabergoline exerts pituitary D2-receptor-mediated inhibition of ACTH secretion and may provide partial cortisol control in selected patients, although treatment escape and variable durability remain important limitations. Osilodrostat is a potent 11β-hydroxylase inhibitor that produces rapid and often substantial reductions in cortisol secretion, with clinical improvement in metabolic and cardiovascular features of hypercortisolism. The osilodrostat-cabergoline combination is mechanistically attractive because it pairs central ACTH suppression with peripheral blockade of cortisol synthesis, but published evidence remains limited to small real-world experiences and does not yet define optimal sequencing, dosing, or long-term benefit. Safety considerations include adrenal insufficiency from overtreatment, osilodrostat-associated hypertension from mineralocorticoid precursor accumulation, and hyperandrogenism due to steroid precursor shunting.

Combination medical therapy in Cushing disease is a promising individualized approach, and the osilodrostat-cabergoline pairing is biologically plausible and potentially effective, but current literature is insufficient to support firm recommendations regarding efficacy, safety, or patient selection.

The study aims to evaluate whether a combination can result in rapid, more control of Cushing's disease (clinically and biochemically)? Can cabergoline reduces Osilodrostat dose requirement, reduces Osilodrostat related mineralocorticoid and hyperandrogenism side effects?

Read the detailed description

In this study, adult patients with active CD (with or without previous TSS or radiotherapy) will be enrolled. Investigators will start treatment for all with Osilodrostat using up-titrating doses on bi-weekly bases. Then the patients will be randomized into two groups. For the first group, carbergoline with escalating doses will be added. For the second group, the patients will continue osilodrostat treatment with increasing doses. Through the period of the study interventions, the patients will be followed clinically, and biochemical looking for treatment related efficacy and safety.

02

Conditions studied

  • Cushing Disease Due to Increased ACTH Secretion

Keywords

  • Cushing's disease
  • Osilodrostat
  • cabergoline
  • adrenal insufficiency
  • hypertension
  • hypokalemia
  • Hyperandrogenism
  • serum cortisol
  • serum dehydroepiandrosterone acetate
  • adrenocorticotrophic hormone
  • QT interval
03

In context

Pituitary ACTH Hypersecretion

64 studies on the registry are indexed under Pituitary ACTH Hypersecretion; 16 are open to participants now.

This study's planned enrollment of 50 is above the median of 44 across 40 interventional studies indexed under Pituitary ACTH Hypersecretion.

Browse Pituitary ACTH Hypersecretion studies →

Lead sponsor

University of Basrah is the lead sponsor of 8 studies on the registry; 7 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

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.

Inclusion criteria

  • Cushing's disease: Not treated or received treatment (TSS and/or radio surgery). And
  • Active disease confirmed with repeated two biochemical tests (1-mg overnight dexamethasone suppression test and late night salivary cortisol), And
  • Inappropriate ACTH elevation, And
  • Positive ACTH response to desmopressin stimulation test, And
  • MRI finding of pituitary adenoma.

Exclusion criteria

Exclusion Criteria:

  • Severe hepatic impairment ( C).
  • Pregnancy.
Terms in these criteria, in plain language(1)

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.

Child-Pugh class

A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.

05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
50 participants (estimated)

Study arms

  • Active comparator
    Osilodrostat alone

    Osilodrostat up to 15 mg daily

    Drug: osilodrostat

  • Active comparator
    Combination osilodrostat and cabergoline

    Osilodrostat up to 5 mg daily plus Cabergoline up to 3 mg weekly

    Drug: osilodrostat and cabergoline

Interventions

  • 1 mg (pill) twice daily for two weeks, titrated to 2.5 mg (5 mg pill divided) twice daily for two weeks, then 7.5 (half 5 mg pill and 5 mg pill) for four weeks, then 10 mg (5 mg pill twice daily) for four weeks, then 15 mg (5 mg pill thrice daily).

  • Drugosilodrostat and cabergoline

    Drug pages: Osilodrostat · Cabergoline

    1 mg (pill) twice daily for two weeks, titrated to 2.5 mg (5 mg pill divided) twice daily for two weeks, then Add: Cabergoline 0.5 mg twice weekly for four weeks, titrated to 1 mg twice weekly for four weeks, then 1 mg thrice weekly.

06

What researchers measure

Primary outcomes

  1. Changes in serum cortisol

    serum cortisol (8-9 am and 6-7 pm).

    Time frame: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, 48 weeks.

  2. Number of patients achieved serum cortisol (7-12 Mg/dL)

    measurement of 8-9 am serum cortisol.

    Time frame: 4 weeks, 8 weeks, 12 weeks, 24, weeks, 36 weeks, and 48 weeks.

  3. Changes in Cushing 's Quality-of-Life questionnaire 12-items (CushingQoL) score for the patients quality of life.

    Changes in CushingQoL (12 items) questionnaire. The lowest score is 12 and highest score is 60. The highest the score, the better life quality and clinical improvement in Cushing syndrome.

    Time frame: At 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

Secondary outcomes

  1. Changes in the patients' Body weight (kg)

    measurement of the patients' body weight using scale in the early morning and fasting, bare feet, light clothes, using electronic scale.

    Time frame: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

  2. Changes in the patients' Blood pressure (increase or decrease) and increase or decrease requirements for blood pressure lowering medications.

    Measurement of the patients' blood pressure (SBP/DBP mmHg) using standard electronic arm cuff blood pressure machine.

    Time frame: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

  3. Changes in HbA1c (%)

    measurement of the patients HbA1c % using BioRad D10

    Time frame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

  4. Assessment of clinical hyperandrogenic features (acne and hirsutism), whether increase or decrease for female patients

    Acne will be assessed by clinical examination and reported as improved or increased. Hirsutism will be assessed using the changes in the modified Ferrimann-Gallwey (mFG) score (0 - 36), the highest the score, the more severe hirsutism.

    Time frame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

  5. Changes in plasma ACTH

    measurement of early morning plasma ACTH (pg/ml)

    Time frame: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

  6. Changes in serum dehydroepiandrosterone acetate (Mg/dl)

    measurement of serum dehydroepiandrosterone acetate (Mg/dl)

    Time frame: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

  7. Changes in the corrected QT interval on electrocardiograph (ECG).

    Performance of ECG for assessment and record of the c QT interval.

    Time frame: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

  8. Changes in serum potassium

    measurement of serum potassium

    Time frame: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

  9. Development of symptoms of hypoadrenalism

    Development of symptoms of hypoadrenalism in the form of (anorexia, nausea, vomiting, fatigue, abdominal pain, dizziness, and hypotension)

    Time frame: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

  10. Number of patients will have morning serum cortisol less than (5 Mg/dl)

    measurement of serum cortisol in the morning and fasting state.

    Time frame: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

Other outcomes

  1. Other drug related side effects

    Side effects of Osilodrostat and cabergoline

    Time frame: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

07

Study locations

5 sites
  • Faiha Specialized Diabetes, Endocrine, and Metabolism Center
    Basra, 61001, Iraq
  • Al-Hassan Metabolism Endocrine and Diabetes Center
    Karbala, Iraq
  • Al-Waffa Specialized Center for Diabetes and Endocrinology
    Mosul, Iraq
  • Najaf Specialized Diabetes and Endocrine Center
    Najaf, Iraq
  • Thi-Qar Specialized Diabetes, Endocrine and Metabolism Center
    Nasiriyah, Iraq
08

References and documents

Publications

  • Ferriere A, Cortet C, Chanson P, Delemer B, Caron P, Chabre O, Reznik Y, Bertherat J, Rohmer V, Briet C, Raingeard I, Castinetti F, Beckers A, Vroonen L, Maiter D, Cephise-Velayoudom FL, Nunes ML, Haissaguerre M, Tabarin A. Cabergoline for Cushing's disease: a large retrospective multicenter study. Eur J Endocrinol. 2017 Mar;176(3):305-314. doi: 10.1530/EJE-16-0662. Epub 2016 Dec 22. PubMed 28007845 ↗
  • Giustina A, Uygur MM, Frara S, Barkan A, Biermasz NR, Chanson P, Freda P, Gadelha M, Haberbosch L, Kaiser UB, Lamberts S, Laws E, Nachtigall LB, Popovic V, Schilbach K, Lely AJV, Wass JAH, Melmed S, Casanueva FF. Medical management pathways for Cushing's disease in pituitary tumors centers of excellence (PTCOEs). Pituitary. 2025 Jan 29;28(1):23. doi: 10.1007/s11102-024-01485-x. PubMed 39881009 ↗
  • Gadelha M, Bex M, Feelders RA, Heaney AP, Auchus RJ, Gilis-Januszewska A, Witek P, Belaya Z, Yu Y, Liao Z, Ku CHC, Carvalho D, Roughton M, Wojna J, Pedroncelli AM, Snyder PJ. Randomized Trial of Osilodrostat for the Treatment of Cushing Disease. J Clin Endocrinol Metab. 2022 Jun 16;107(7):e2882-e2895. doi: 10.1210/clinem/dgac178. PubMed 35325149 ↗
  • Vilar L, Naves LA, Machado MC, Bronstein MD. Medical combination therapies in Cushing's disease. Pituitary. 2015 Apr;18(2):253-62. doi: 10.1007/s11102-015-0641-x. PubMed 25647330 ↗

Individual participant data

Plan to share: Yes — Only IPD used in the results publication.

Supporting information: Study protocol, Statistical analysis plan

Time frame: Beginning 3 months and ending 3 years after the publication of results.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started May 2026 (actual). Primary completion is estimated for Jun 2028, 25 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
May 11, 2026
First posted
May 22, 2026
StartActual
May 11, 2026
Primary completionEst.
Jun 2028
CompletionEst.
Aug 2028
Last update
May 22, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on May 22, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07603466
Lead sponsor
University of Basrah
Responsible party
Haider Ayad Alidrisi (Assistant Professor, University of Basrah) — Principal investigator
First posted
May 22, 2026
Start date
May 11, 2026
Primary completion
Jun 2028 (estimated)
Completion
Aug 2028 (estimated)
Last update
May 22, 2026

Study contacts

Haider A Alidrisi
principal investigator · Univeristy of basrah, Faiha Specialized Diabetes, Endocrine, and Metabolism Center
Ibrahim H Hussein, MD
principal investigator · Univeristy of basrah, Faiha Specialized Diabetes, Endocrine, and Metabolism Center
Abbas A Mansour
study chair · Univeristy of basrah, Faiha Specialized Diabetes, Endocrine, and Metabolism Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

No contact was published for this record. The registry link below has the sponsor’s details.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drugs tested here: Osilodrostat · Cabergoline

Start the discussion