The Use of Propranolol in the Perioperative Period of Resectable Gastrointestinal Tumors

Официальное название

The Use of Propranolol in the Perioperative Period of Resectable Gastrointestinal Tumors and the Study of Its Immune Mechanism Research

Обзор

In this study, perioperative propranolol β-blockade was administered to patients with surgically resectable primary gastrointestinal tumors to explore the safety, efficacy, and alleviation of perioperative psychological stress. At the same time, a multi-omics study was conducted using clinical samples to explore the activation of anti-tumor immune response and its mechanism.

Подробное описание

This is a single-center, randomized controlled pilot exploratory clinical study to enroll 20 patients with surgically resectable primary gastric cancer and 20 patients with surgically resectable primary colorectal cancer. Each enrolled patient will be assigned a case number. This case number and the patient's initials will be entered on each page of the case report form. Trial group (10 patients with gastric cancer and 10 patients with intestinal cancer): Enrolled patients will be hospitalized for 10-14 days of preoperative propranolol β-blockade monotherapy prior to surgery (including the day of surgery) for evaluation of efficacy and safety. Control group (10 cases of gastric cancer and 10 cases of intestinal cancer): no propranolol drug treatment. Patients will be observed during the treatment period and at 6 months, 12 months and 24 months after treatment.

Вмешательства

• Препарат propranolol (beta-blocker used treat high blood pressure)
  Enrolled patients began receiving propranolol alone orally twice daily (10 mg bid) 10-14 days prior to surgery, and after 3 days of treatment, the dose of propranolol was increased to 20 mg bid daily until the day of surgery if the following three predefined criteria were met: systolic blood pressure greater than 90 mmHg, heart rate greater than 60 bpm, and no significant symptoms (e.g., syncope, insomnia, fatigue). The patient continues to be treated from 1 week after surgery.From 1 week after

Первичные конечные точки

• Anxiety Depression Scale Scores [Срок оценки: Within two years of enrollment]
• heart rate [Срок оценки: From enrollment to 24 days postoperatively]
• Heart rate variability [Срок оценки: From enrollment to 24 days postoperatively]
• blood preasure [Срок оценки: From enrollment to 24 days postoperatively]
• Norepinephrine levels [Срок оценки: From enrollment to 24 days postoperatively]
• blood glucose [Срок оценки: From enrollment to 24 days postoperatively]
• SaO2 [Срок оценки: From enrollment to 24 days postoperatively]
• RNA-seq of tumor tissue [Срок оценки: Baseline and during surgery]
• RNA-seq of peripheral blood PBMCs [Срок оценки: Baseline and during surgery]
• Flow cytometry of peripheral blood PBMC [Срок оценки: Baseline and during surgery]

Вторичные конечные точки (2)

• 2-year OS rate [Срок оценки: Two years after surgery]
• 2-year RFS rate [Срок оценки: Two years after surgery]

Критерии участия

Критерии включения

• Surgically resectable primary gastric cancer and colorectal cancer;
• Age greater than 18 years old and less than 65 years old;
• Negative pregnancy test for women of childbearing age;
• ECOG score ≤2;
• Signed informed consent.
• Resting blood pressure greater than 100/60mmHg, heart rate greater than 60 beats per minute.

Exclusion Criteria：

1\) Pregnant or breastfeeding women, or women with pregnancy plans within six months; 2) Patients with absolute or relative contraindications to propranolol:

• Pathological sinus node syndrome;
• Sinus bradycardia (less than 60 beats/minute);
• First, second or third degree AV block;
• Resting blood pressure less than 100/60 mmHg;
• untreated pheochromocytoma;
• untreated thyroid disease;
• Patients on dihydropyridine or non-dihydropyridine calcium channel blockers (e.g., diltiazem, verapamil, nifedipine, amlodipine);
• Severe peripheral vascular disease (intermittent claudication);
• Patients on antiarrhythmic drugs (e.g., amiodarone, sotalol, digoxin);
• Patients with renal insufficiency (defined as creatinine clearance greater than 0.15 mmol/L);
• Patients with hepatic insufficiency: AST or ALT or ALP > 2.5 times the upper limit of normal (ULN), bilirubin > 1.5 times the ULN, ALP > 2.5
• Patients using colistin, digoxin, rizatriptan, cimetidine, hydralazine, guanethidine, or ergotamine.
• Patients with a history of major depressive episodes; 3) Patients who have undergone surgery for GI tumors within the previous six months; 4) Patients receiving neoadjuvant chemotherapy prior to planned gastrointestinal tumor resection; 5) patients using conventional anxiolytic drugs (e.g. benzodiazepines), alpha-adrenergic agonists (e.g. colistin); 6) Patients using selective or non-selective β-adrenergic inhibitors (e.g., propranolol, metoprolol, atenolol, sotalol) within the last three months; 7) Patients with a history of stroke; 8) Patients with moderate or severe asthma, defined as requiring hospitalization or oral steroid therapy; (9) Those who, in the opinion of the physician, have other reasons for not being included in the treatment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Huashan Hospital, Fudan University — Шанхай

Идентификаторы

NCT: NCT06775080 · KY2024-1317

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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