Combination Osilodrostat and Cabergoline in Cushing's Disease (COSCA-ECD)
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?
調査の概要
詳細な説明
研究の種類
入学 (推定)
段階
- フェーズ 4
連絡先と場所
研究場所
-
-
-
Basra、イラク、61001
- Faiha Specialized Diabetes, Endocrine, and Metabolism Center
-
Karbala、イラク
- Al-Hassan Metabolism Endocrine and Diabetes Center
-
Mosul、イラク
- Al-Waffa Specialized Center for Diabetes and Endocrinology
-
Najaf、イラク
- Najaf Specialized Diabetes and Endocrine Center
-
Nasiriyah、イラク
- Thi-Qar Specialized Diabetes, Endocrine and Metabolism Center
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：順次割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ：Osilodrostat alone
Osilodrostat up to 15 mg daily
|
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).
|
|
アクティブコンパレータ：Combination osilodrostat and cabergoline
Osilodrostat up to 5 mg daily plus Cabergoline up to 3 mg weekly
|
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.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Changes in serum cortisol
時間枠：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)
時間枠：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.
時間枠：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.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Changes in the patients' Body weight (kg)
時間枠：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.
時間枠：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 (%)
時間枠：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
時間枠：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
時間枠：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)
時間枠：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).
時間枠：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
時間枠：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
時間枠：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)
時間枠：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.
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Other drug related side effects
時間枠：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.
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Haider A Alidrisi、Univeristy of basrah, Faiha Specialized Diabetes, Endocrine, and Metabolism Center
- 主任研究者：Ibrahim H Hussein, MD、Univeristy of basrah, Faiha Specialized Diabetes, Endocrine, and Metabolism Center
- スタディチェア：Abbas A Mansour、Univeristy of basrah, Faiha Specialized Diabetes, Endocrine, and Metabolism Center
出版物と役立つリンク
一般刊行物
- 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.
- 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.
- 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.
- 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.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
- 泌尿生殖器疾患
- 内分泌系疾患
- 脳疾患
- 中枢神経系疾患
- 神経系疾患
- 血管疾患
- 心血管疾患
- 男性の泌尿生殖器疾患
- 女性の泌尿生殖器疾患
- 女性の泌尿生殖器疾患と妊娠合併症
- 代謝疾患
- 性腺疾患
- 先天異常
- 水電解質の不均衡
- 副腎疾患
- 性発達障害
- 泌尿生殖器の異常
- 視床下部疾患
- 下垂体機能亢進症
- 下垂体疾患
- 46、XX性発達障害
- 副腎性器症候群
- 先天性、遺伝性、および新生児の疾患と異常
- 栄養および代謝疾患
- 高血圧症
- 下垂体ACTH過剰分泌
- 副腎不全
- 高アンドロゲン症
- 低カリウム血症
- 複素環化化合物
- 複素環化化合物、融合リング
- アルカロイド
- 複素環化化合物、4つ以上のリング
- エルゴットアルカロイド
- エルゴリン
- カベルゴリン
- オシロドロスタット
その他の研究ID番号
- 05/13/26
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
IPD 共有時間枠
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。