Pharmacologic Therapies to Mitigate Radiation- Associated Heart Disease
Radiation therapy is an essential treatment for tumors in the chest area, including breast, lung, esophageal, mediastinal cancers, and spine metastases. Although technical advances have reduced treatment-related illness and death, radiation exposure to the heart can still cause substantial rates of radiation-induced heart disease (RIHD) among survivors.
For example, about 21% of non-small cell lung cancer patients receiving a mean heart dose of 20 Gy or higher experience major adverse cardiac events (MACE) within 2 years. In breast cancer patients, the risk of MACE increases by about 7% for each additional Gy of mean heart dose.
There is currently no established medication strategy to prevent or reduce RIHD.
Preclinical and clinical studies show that statins and angiotensin-converting enzyme (ACE) inhibitors may help reduce radiation-induced heart disease (RIHD). Statins and ACE inhibitors are generally well tolerated, available as generic drugs, and commonly used to help prevent cardiovascular disease. They may protect the heart by reducing damage to blood vessel lining (endothelial damage), microvascular dysfunction, atherosclerosis, reduced blood flow (ischemia), and fibrosis (scarring).
This study is a prospective, randomized, placebo-controlled phase II hybrid decentralized trial. Patients receiving standard radiation therapy and expected to receive an equivalent dose of at least 25 Gy (EQD2) to at least 10% of the heart will be randomly assigned to receive either:
- placebo, or
- Atorvastatin 20 mg plus Lisinopril 5 mg daily. The medications will be taken during radiation therapy and continued for 6 months after treatment.
The study aims to determine whether the intervention can reduce radiation-related decreases in blood flow to the heart, measured using myocardial perfusion imaging, such as positron emission tomography (PET), which is commonly used to evaluate the risk of coronary heart disease.
調査の概要
状態
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：Claire Kowalczyk
- 電話番号：984-974-0000
- メール：claire_kowalczyk@med.unc.edu
研究場所
-
-
North Carolina
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Chapel Hill、North Carolina、アメリカ、27599
- 募集
- Lineberger Comprehensive Cancer Center at University of North Carolina, Chapel Hill
-
主任研究者：
- Shivani Sud, MD
-
コンタクト：
- Claire Kowalczyk
- 電話番号：984-974-0000
- メール：claire_kowalczyk@med.unc.edu
-
-
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:
- Written informed consent obtained to participate in the study and HIPAA
- authorization for release of personal health information.
- Subjects is willing and able to comply with study procedures based on the
- judgement of the investigator.
- Consent for serial blood draws and consent for use of biological specimens.
- Age ≥ 18 years at the time of consent
Exclusion Criteria:
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
- Pre-existing use of a statin or ACE-inhibitor
- Pre-existing hypotension
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：支持療法
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：statins and angiotensin-converting enzyme (ACE) inhibitors
Patients expected to receive ≥25 Gy equivalent dose in 2 Gy fractions (EQD2) to at least 10% of the heart will be treated with statins and angiotensin-converting enzyme (ACE) inhibitors.
|
Patients will receive statins and angiotensin-converting enzyme (ACE) inhibitors.
|
|
プラセボコンパレーター：Placebo
Patients expected to receive ≥25 Gy equivalent dose in 2 Gy fractions (EQD2) to at least 10% of the heart will take inhibitors.
|
患者にはプラセボが投与されます。
|
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 |
|---|---|---|
|
Percent difference in the radiation (RT)-induced reduction of myocardial perfusion
時間枠：Pre radiation therapy and 6-month post radiation therapy
|
Percent difference in the radiation (RT)-induced reduction of myocardial perfusion in cardiac regions receiving ≥25Gy equivalent dose in 2Gy fractions (EQD2) based on comparison of before and after RT among participants receiving placebo and statins and angiotensin-converting enzyme (ACE) inhibitors intervention.
|
Pre radiation therapy and 6-month post radiation therapy
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Percent Change in Radiation-Induced Myocardial Perfusion Reduction by Cardiac Dose: Placebo vs Statin and ACE Inhibitor Therapy
時間枠：Pre radiation therapy and 6-month post radiation therapy
|
Percent difference in radiation therapy (RT)-induced reduction of myocardial perfusion in cardiac regions receiving different radiation doses (10-20 Gy and 20-25 Gy equivalent dose in 2 Gy fractions, EQD2), based on comparison of pre-RT and 6-month post-RT myocardial perfusion imaging scans between participants receiving placebo versus statins and angiotensin-converting enzyme (ACE) inhibitors intervention.
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Pre radiation therapy and 6-month post radiation therapy
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Change in for cardiac biomarker panel
時間枠：Pre radiation therapy and 3 months and 6-month post radiation therapy
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Change in for cardiac biomarker panel including high- sensitivity troponin, Creatine Kinase myocardial band (CK-MB) or N-terminal pro-B-type Natriuretic Peptide( NT-proBNP).
|
Pre radiation therapy and 3 months and 6-month post radiation therapy
|
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Correlation between cardiac stress and perfusion biomarkers and radiation dose
時間枠：Pre radiation therapy and 3 months and 6-month post radiation therapy
|
Correlations between absolute values and changes in cardiac stress/perfusion biomarkers and radiation dose at the individual pixel level will be compared between the placebo and intervention groups.
Cardiac perfusion imaging provides quantitative assessment of regional myocardial perfusion, and the absolute difference in RT-induced perfusion reduction between study arms will be evaluated using pre- and post-RT measurements.
Changes in cardiac biomarkers, including high- sensitivity troponin, Creatine Kinase myocardial band (CK-MB) or N-terminal pro-B-type Natriuretic Peptide( NT-proBNP).
will also be assessed.
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Pre radiation therapy and 3 months and 6-month post radiation therapy
|
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Rates of major adverse cardiac events
時間枠：At follow-up of 1, 2, and 3 years.
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Rates of major adverse cardiac events (unstable angina, heart failure hospitalization or urgent visit, myocardial infarction, coronary revascularization, and cardiac death) will be compared between trial groups at long-term
|
At follow-up of 1, 2, and 3 years.
|
協力者と研究者
捜査官
- 主任研究者：Shivani Sud, MD、UNC Lineberger Comprehensive Cancer Center
出版物と役立つリンク
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
その他の研究ID番号
- LCCC2239-DCT
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?
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。
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