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Combination Osilodrostat and Cabergoline in Cushing's Disease (COSCA-ECD)

15. maj 2026 opdateret af: Haider Ayad Alidrisi, University of Basrah

Combination Osilodrostat and Cabergoline Versus Osilodrostat Alone in Cushing's Disease in Iraq: Assessment of Efficacy and Safety

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?

Studieoversigt

Status

Tilmelding efter invitation

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

50

Fase

  • Fase 4

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

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:

  • Severe hepatic impairment (Child-Pugh C).
  • Pregnancy.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Sekventiel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: Osilodrostat alone
Osilodrostat up to 15 mg daily
Medicin: osilodrostat
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).
Aktiv komparator: Combination osilodrostat and cabergoline
Osilodrostat up to 5 mg daily plus Cabergoline up to 3 mg weekly
Medicin: osilodrostat and 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.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Changes in serum cortisol
Tidsramme: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, 48 weeks.
serum cortisol (8-9 am and 6-7 pm).
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, 48 weeks.
Number of patients achieved serum cortisol (7-12 Mg/dL)
Tidsramme: 4 weeks, 8 weeks, 12 weeks, 24, weeks, 36 weeks, and 48 weeks.
measurement of 8-9 am serum cortisol.
4 weeks, 8 weeks, 12 weeks, 24, weeks, 36 weeks, and 48 weeks.
Changes in Cushing 's Quality-of-Life questionnaire 12-items (CushingQoL) score for the patients quality of life.
Tidsramme: At 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
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.
At 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Changes in the patients' Body weight (kg)
Tidsramme: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
measurement of the patients' body weight using scale in the early morning and fasting, bare feet, light clothes, using electronic scale.
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Changes in the patients' Blood pressure (increase or decrease) and increase or decrease requirements for blood pressure lowering medications.
Tidsramme: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Measurement of the patients' blood pressure (SBP/DBP mmHg) using standard electronic arm cuff blood pressure machine.
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Changes in HbA1c (%)
Tidsramme: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
measurement of the patients HbA1c % using BioRad D10
At 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Assessment of clinical hyperandrogenic features (acne and hirsutism), whether increase or decrease for female patients
Tidsramme: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

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.
At 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Changes in plasma ACTH
Tidsramme: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
measurement of early morning plasma ACTH (pg/ml)
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Changes in serum dehydroepiandrosterone acetate (Mg/dl)
Tidsramme: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
measurement of serum dehydroepiandrosterone acetate (Mg/dl)
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Changes in the corrected QT interval on electrocardiograph (ECG).
Tidsramme: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Performance of ECG for assessment and record of the c QT interval.
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Changes in serum potassium
Tidsramme: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
measurement of serum potassium
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Development of symptoms of hypoadrenalism
Tidsramme: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Development of symptoms of hypoadrenalism in the form of (anorexia, nausea, vomiting, fatigue, abdominal pain, dizziness, and hypotension)
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Number of patients will have morning serum cortisol less than (5 Mg/dl)
Tidsramme: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
measurement of serum cortisol in the morning and fasting state.
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

Andre resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Other drug related side effects
Tidsramme: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Side effects of Osilodrostat and cabergoline
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

University of Basrah

Efterforskere

  • Ledende efterforsker: Haider A Alidrisi, Univeristy of basrah, Faiha Specialized Diabetes, Endocrine, and Metabolism Center
  • Ledende efterforsker: Ibrahim H Hussein, MD, Univeristy of basrah, Faiha Specialized Diabetes, Endocrine, and Metabolism Center
  • Studiestol: Abbas A Mansour, Univeristy of basrah, Faiha Specialized Diabetes, Endocrine, and Metabolism Center

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

11. maj 2026

Primær færdiggørelse (Anslået)

1. juni 2028

Studieafslutning (Anslået)

1. august 2028

Datoer for studieregistrering

Først indsendt

11. maj 2026

Først indsendt, der opfyldte QC-kriterier

15. maj 2026

Først opslået (Faktiske)

22. maj 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

22. maj 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

15. maj 2026

Sidst verificeret

1. maj 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 05/13/26

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

Only IPD used in the results publication.

IPD-delingstidsramme

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

IPD-deling Understøttende informationstype

  • STUDY_PROTOCOL
  • SAP

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