Study of Propranolol as Anti-Adhesive Therapy in Sickle Cell Disease (SCD)
2015年1月19日 更新者：Laura M. De Castro, MD
Phase II Study of Propranolol as Anti-Adhesive Therapy for Sickle Cell Disease
An open label, prospective, randomized cross-over phase II study in up to 60 sickle cell patients who are either homozygous for Hb S or have HbSB0 thalassemia. Initially, each patient will be treated for 6 weeks with placebo or a standard dose of propranolol (40 mg) every 12 hrs. This will be followed by a 2-week washout period after which, patients will receive the other treatment modality (placebo or propranolol).
We Hypothesize that propranolol administered in vivo on a daily basis for 6 weeks (1) will decrease baseline adhesion to endothelial cells and will substantially abrogate epinephrine-stimulated adhesion to endothelial cells, as measured in vitro; (2) will improve biomarkers of endothelial activation and dysfunction; and (3) can be safely used in patients with SCD. Thus, the use of propranolol in SCD may represent a safe and effective means of anti-adhesive therapy in SCD.
Study Objectives:
Primary Objective:
• To establish the safety and efficacy of long-term therapy with propranolol as an anti-adhesive therapy for SCD.
Secondary Objective:
• To evaluate changes in soluble markers of endothelial activation and dysfunction.
Correlative Science Objective:
• To determine whether response to propranolol therapy is associated with polymorphisms in genes encoding the proteins involved in the upregulation of Sickle Red Blood Cell (SS RBC) adhesion by epinephrine.
調査の概要
研究の種類
介入
入学 (実際)
31
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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North Carolina
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Durham、North Carolina、アメリカ、27710
- Duke University Medical Center
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- Diagnosis by electrophoresis (HEP) of Hemoglobin (Hgb) SS or Hgb Sβ0 thalassemia (all patients followed at our clinic have HEP-confirmed diagnosis on file)
- Age ≥ 18 years
- Blood pressure (BP) Systolic ≥ 95mm Hg and Diastolic ≥ 50mm Hg
- Heart rate (HR) ≥ 70 and ≤ 110 bpm
- Oxygen saturation by pulse oximeter and at room air ≥ 92%
- Hematocrit (Hct) ≥ 20% and Hb > 6.0 g/dL
- Euthyroid status as indicated by normal Thyroid Stimulating Hormone (TSH)
- SS RBCs obtained during screening period demonstrating an adhesion response to epinephrine of 40% over non-stimulated baseline adhesion to endothelial cells
- Capacity to understand and sign informed consent
Exclusion Criteria:
- History of vaso-occlusive episode during the 6 wks prior to screening
- RBC transfusion during the 3 months prior to study entry
- Ongoing pregnancy
- History of heart failure, myocardial infarct (MI), bradyarrhythmias, conduction defects
- History of asthma or reactive airway disease
- History of thyroid disease
- Diabetes
- Renal insufficiency (BUN >21 mg/dL and/or Creatinine >1.4 mg/dL)
- Use during the screening or study period of any of the following medications: antihypertensives, diuretics, thyroid replacement therapy, anti-arrhythmia medications, bronchodilators, inhaled steroids, insulin, or hypoglycemic medication
- History of allergy to sulfonamides
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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：ランダム化
- 介入モデル：クロスオーバー割り当て
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
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プラセボコンパレーター：シュガーピル
プラセボ群
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Treatment will be with a standard propranolol dose of 40 mg every 12 hrs.Each patient will participate in 6 weeks of treatment with placebo or study drug (propranolol), followed by a 2-week wash-out period and then 6 weeks of treatment with the other modality (placebo or propranolol).
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実験的：Propranolol
Drug arm
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Treatment will be with a standard propranolol dose of 40 mg every 12 hrs.Each patient will participate in 6 weeks of treatment with placebo or study drug (propranolol), followed by a 2-week wash-out period and then 6 weeks of treatment with the other modality (placebo or propranolol).
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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 |
|---|---|---|
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SS RBC Adhesion (Epi -1d/cm2- vs. Sham) by Treatment
時間枠：Week 0 to 6 and week 8 to 14
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The stickiness of SS RBC will be evaluated by a well-established in vitro assay of adhesion of SS RBCs to cultured endothelial cells using a flow chamber.
Overall change of adhesion from baseline to post intervention( Week 0 to 6 and week 8 to 14) in unstimulated cells (Sham treated) vs. Stimulated Red Blood Cells (Epi-treated) at 1 dyne/cm2
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Week 0 to 6 and week 8 to 14
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SS RBC Adhesion (Epi -2d/cm2- vs. Sham) by Treatment
時間枠：Week 0 to 6 and week 8 to 14
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The stickiness of SS RBC will be evaluated by a well-established in vitro assay of adhesion of SS RBCs to cultured endothelial cells using a flow chamber.
Overall change of adhesion from baseline to post intervention( Week 0 to 6 and week 8 to 14) in unstimulated cells (Sham treated) vs. Stimulated Red Blood Cells (Epi-treated) at 2 dyne/cm2
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Week 0 to 6 and week 8 to 14
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SS RBC Adhesion (Epi -3d/cm2- vs. Sham) by Treatment
時間枠：Week 0 to 6 and week 8 to 14
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The stickiness of SS RBC will be evaluated by a well-established in vitro assay of adhesion of SS RBCs to cultured endothelial cells using a flow chamber.
Overall change of adhesion from baseline to post intervention( Week 0 to 6 and week 8 to 14) in unstimulated cells (Sham treated) vs. Stimulated Red Blood Cells (Epi-treated) at 3 dyne/cm2
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Week 0 to 6 and week 8 to 14
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Overall Change of Plasma Levels of sE-selectin
時間枠：Week 0 to 6 and week 8 to 14
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Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sE-selectin measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 and week 8 to 14).
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Week 0 to 6 and week 8 to 14
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Overall Change of Plasma Levels of sP-selectin
時間枠：Week 0 to 6 and week 8 to 14
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Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sP-selectin measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 and weeks 8 to 14).
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Week 0 to 6 and week 8 to 14
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Overall Change of Plasma Levels of sICAM-1
時間枠：Week 0 to 6 and week 8 to 14
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Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sICAM-1 measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 and week 8 to 14)
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Week 0 to 6 and week 8 to 14
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Overall Change of Plasma Levels of sVCAM-1
時間枠：Week 0 to 6 and week 8 to 14
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Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sVCAM-1 measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 or week 8 to 14)
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Week 0 to 6 and week 8 to 14
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Overall Change of Hemoglobin (Hgb) Levels
時間枠：Week 0 to 6 and week 8 to 14
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Overall change of Hemoglobin (Hgb) levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated
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Week 0 to 6 and week 8 to 14
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Overall Change of Hematocrit (Hct) Levels
時間枠：Week 0 to 6 and week 8 to 14
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Overall change of Hematocrit (Hct) levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated
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Week 0 to 6 and week 8 to 14
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Overall Change of Lactate Dehydrogenase (LDH) Levels
時間枠：Week 0 to 6 and week 8 to 14
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Overall change of LDH levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated
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Week 0 to 6 and week 8 to 14
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Overall Change of Oxygen Saturation (02Sat) Levels
時間枠：Week 0 to 6 and week 8 to 14
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Overall change of Oxygen Saturation (02Sat) levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated
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Week 0 to 6 and week 8 to 14
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Overall Change of Systolic Blood Pressure Levels
時間枠：Week 0 to 6 and week 8 to 14
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Overall change of Systolic Blood Pressure levels from baseline to post intervention (Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated
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Week 0 to 6 and week 8 to 14
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Overall Change of Diastolic Blood Pressure Levels
時間枠：Week 0 to 6 and week 8 to 14
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Overall change of Diastolic Blood Pressure levels from baseline to post intervention (Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated
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Week 0 to 6 and week 8 to 14
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Zennadi R, Chien A, Xu K, Batchvarova M, Telen MJ. Sickle red cells induce adhesion of lymphocytes and monocytes to endothelium. Blood. 2008 Oct 15;112(8):3474-83. doi: 10.1182/blood-2008-01-134346. Epub 2008 Jul 29.
- De Castro LM, Zennadi R, Jonassaint JC, Batchvarova M, Telen MJ. Effect of propranolol as antiadhesive therapy in sickle cell disease. Clin Transl Sci. 2012 Dec;5(6):437-44. doi: 10.1111/cts.12005. Epub 2012 Oct 17.
- Zennadi R, Hines PC, De Castro LM, Cartron JP, Parise LV, Telen MJ. Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-alphavbeta3 interactions. Blood. 2004 Dec 1;104(12):3774-81. doi: 10.1182/blood-2004-01-0042. Epub 2004 Aug 12.
- Zennadi R, Moeller BJ, Whalen EJ, Batchvarova M, Xu K, Shan S, Delahunty M, Dewhirst MW, Telen MJ. Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo. Blood. 2007 Oct 1;110(7):2708-17. doi: 10.1182/blood-2006-11-056101. Epub 2007 Jul 3.
- Eyler CE, Jackson T, Elliott LE, De Castro LM, Jonassaint J, Ashley-Koch A, Telen MJ. beta(2)-Adrenergic receptor and adenylate cyclase gene polymorphisms affect sickle red cell adhesion. Br J Haematol. 2008 Apr;141(1):105-8. doi: 10.1111/j.1365-2141.2008.07008.x.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2010年6月1日
一次修了 (実際)
2013年12月1日
研究の完了 (実際)
2013年12月1日
試験登録日
最初に提出
2010年2月26日
QC基準を満たした最初の提出物
2010年2月26日
最初の投稿 (見積もり)
2010年3月1日
学習記録の更新
投稿された最後の更新 (見積もり)
2015年1月22日
QC基準を満たした最後の更新が送信されました
2015年1月19日
最終確認日
2015年1月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- Pro00018427
- K01HL096434-02 (米国 NIH グラント/契約)
- 5R21HL096123-02 (米国 NIH グラント/契約)
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。
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