小児における門脈圧亢進症の形状
小児における門脈圧亢進症の非侵襲的サブハーモニック支援圧力推定
Early diagnosis of portal hypertension is difficult as symptoms rarely manifest until the later stages of liver disease. Both cirrhotic and non-cirrhotic portal hypertension can result in life-threatening complications, the most frequent of which is bleeding from esophageal varices. In children, variceal bleeds are associated with mortality rates of 1-3 %, while life-threatening complications have been reported in up to 20 % of children with cirrhosis. Despite the high incidence of portal hypertension in children with liver disease, a noninvasive modality to monitor disease progression and risk of complications is currently lacking. Hence, this trial will investigate the safety and efficacy of subharmonic aided pressure estimation (SHAPE) as a noninvasive ultrasound technique for diagnosing portal hypertension in children.
調査の概要
状態
条件
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19104
- The Children's Hospital of Philadelphia
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Patients with a diagnosis of chronic liver disease without portal hypertension.
- Patients with a diagnosis of chronic liver disease with portal hypertension.
Exclusion Criteria:
- Subjects who are pregnant.
- Patients with known or suspected hypersensitivity to egg phosphatidyl serine or with a history of anaphylactic allergy to eggs or egg products.
- Subjects with allergy to egg products or other components of the ultrasound contrast agents will be excluded.
- History of allergic reaction to Lumason®, sulfur hexafluoride, sulfur hexafluoride lipid microsphere components, or other ingredients in Lumason (polyethylene glycol, distearoylphosphatidylcholine (DSPC), dipalmitoylphosphatidylglycerol sodium (DPPG-Na), palmitic acid)
- History of allergic reaction to Sonazoid
- Patients with biliary atresia with asplenia or polysplenia.
- Patients with prior liver transplant.
- Patients with cystic fibrosis.
- Patients with chronic lung disease.
- Patients with portal vein thrombosis, cavernous transformation of the portal vein or absent portal vein.
- Adults not competent/impaired.
- Patients with significant heart disease or severe congenital heart disease
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：診断
- 割り当て：ランダム化
- 介入モデル：並列代入
- 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 |
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実験的：SHAPE with Sonazoid
Up to 60 children (6-21 years of age) with a diagnosis of chronic liver disease, including some who will have portal hypertension who are followed at The Children's Hospital of Philadelphia (CHOP) will be enrolled in this arm. A SHAPE measurement using the ultrasound contrast agent Sonazoid® (perfluorobutane microbubbles) will be performed during a single visit. A dose of three vials with 16 μL each of microbubbles will be prepared. An infusion of the ultrasound contrast agent at the rate of 0.18 mL/kg/hour will be co-infused with an infusion of saline at the rate of 120 mL/hour resulting in an effective dosage of 1.44 μL microbubbles/kg/hour as per the FDA approved IND through an IV line in a peripheral vein. The total duration of contrast agent infusion is expected to range from 4 to 8 minutes, which includes a 2 min calibration period followed by 2-6 minutes of SHAPE acquisition (i.e., ultrasound imaging). |
The ultrasound contrast agent will be infused thorough an IV line and SHAPE ultrasound imaging and data acquisition will be performed with a Logiq E10 (GE Medical Systems, Waukesha, WI) ultrasound scanner. |
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アクティブコンパレータ：SHAPE with Lumason
Up to 60 children (6-21 years of age) with a diagnosis of chronic liver disease, including some who will have portal hypertension who are followed at CHOP will be enrolled in this arm. A SHAPE measurement using the ultrasound contrast agent LUMASON® (sulfur hexafluoride lipid-type A microspheres) will be performed during a single visit. Two doses of 0.03 mL/kg (or 2.4 mL maximum) as per package labeling will be prepared and mixed with saline at a 1:10 dilution in a 50 ml bag of saline. The diluted preparation of Lumason will be through an IV line in a peripheral vein up to 4 mL/min using an infusion setup. The total duration of contrast agent infusion is expected to range from 4 to 8 minutes, which includes a 2 min calibration period followed by 2-6 minutes of SHAPE acquisition (i.e., ultrasound imaging). |
The ultrasound contrast agent will be infused thorough an IV line and SHAPE ultrasound imaging and data acquisition will be performed with a Logiq E10 (GE Medical Systems, Waukesha, WI) ultrasound scanner. |
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実験的：Longitudinal SHAPE
SHAPE will be used to monitor subjects identified in the initial examination as having portal hypertension for up to 18 months. These subjects will undergo laboratory testing every 6 months as a part of their clinical standard of care. During these times the SHAPE examination will also be repeated using the same ultrasound contrast agent and infusion methodologies (including dosages) as during the initial study. |
The ultrasound contrast agent will be infused thorough an IV line and SHAPE ultrasound imaging and data acquisition will be performed with a Logiq E10 (GE Medical Systems, Waukesha, WI) ultrasound scanner. The ultrasound contrast agent will be infused thorough an IV line and SHAPE ultrasound imaging and data acquisition will be performed with a Logiq E10 (GE Medical Systems, Waukesha, WI) ultrasound scanner. |
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 |
時間枠 |
|---|---|
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小児用ルマソンの添付文書で報告されている有害事象の現在の発生率 (0.001%) と比較した、Sonazoid で発生する有害事象の発生率 (%)
時間枠：2時間
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2時間
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門脈と肝静脈の間の調整されたサブハーモニック マイクロバブル信号 (dB) は、門脈圧亢進症と非門脈圧亢進症のグループを 94% の精度で区別します。
時間枠：2時間
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2時間
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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経時的な門脈と肝静脈の間の較正された低調波マイクロバブル信号 (dB) の変化は、門脈圧亢進症 (静脈瘤出血、腹水、肝肺症候群など) の合併症の発生を予測します。
時間枠：平均18ヶ月
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平均18ヶ月
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門脈と肝静脈と肝線維化段階 (肝生検で決定される 0 ～ 4 のスケール) の間の調整されたサブハーモニック マイクロバブル信号 (dB) は、p<0.05 と相関します。
時間枠：2時間
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2時間
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門脈圧亢進症群と非門脈圧亢進症群を区別する能力について、それぞれ Lumason と Sonazoid で得られた門脈と肝静脈の間の校正済みサブハーモニック マイクロバブル信号 (dB) を比較します。
時間枠：2時間
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2時間
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回帰分析を使用して、門脈と肝静脈の間の較正された低調波マイクロバブル信号 (dB) をせん断波エラストグラフィ値 (m/s) と比較します
時間枠：2時間
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2時間
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協力者と研究者
協力者
捜査官
- 主任研究者：Sudha A Anupindi, MD、Children's Hospital of Philadelphia
- 主任研究者：Flemming Forsberg, PhD、Thomas Jefferson University
出版物と役立つリンク
一般刊行物
- Eisenbrey JR, Dave JK, Halldorsdottir VG, Merton DA, Miller C, Gonzalez JM, Machado P, Park S, Dianis S, Chalek CL, Kim CE, Baliff JP, Thomenius KE, Brown DB, Navarro V, Forsberg F. Chronic liver disease: noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient. Radiology. 2013 Aug;268(2):581-8. doi: 10.1148/radiol.13121769. Epub 2013 Mar 22.
- Gupta I, Eisenbrey JR, Machado P, Stanczak M, Wessner CE, Shaw CM, Gummadi S, Fenkel JM, Tan A, Miller C, Parent J, Schultz S, Soulen MC, Sehgal CM, Wallace K, Forsberg F. Diagnosing Portal Hypertension with Noninvasive Subharmonic Pressure Estimates from a US Contrast Agent. Radiology. 2021 Jan;298(1):104-111. doi: 10.1148/radiol.2020202677. Epub 2020 Nov 17.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
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
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
Data generated from the proposed study will be shared to make the results available to the scientific community.
Presentations at national scientific meetings.
Lectures.
Post-graduate training.
Approximately 12 months after the completion of the trial (when the main manuscript has been published) individual researchers can contact the PIs and request the final, complete data-set from this trial without any protected health information
IPD 共有時間枠
Approximately 12 months after the completion of the trial when the main manuscript has been published
IPD 共有アクセス基準
On an individual basis - contact the PIs
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
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
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。