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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastrointestinal Tumors
• Intervention / Treatment: Drug: propranolol (beta-blocker used treat high blood pressure)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Recruiting
      • Huashan Hospital, Fudan University
      • Contact: Wanwei Zheng; Phone Number: 13816431448; Email: calebzww@yeah.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Surgically resectable primary gastric cancer and colorectal cancer;
2. Age greater than 18 years old and less than 65 years old;
3. Negative pregnancy test for women of childbearing age;
4. ECOG score ≤2;
5. Signed informed consent.
6. 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:

1. Pathological sinus node syndrome;
2. Sinus bradycardia (less than 60 beats/minute);
3. First, second or third degree AV block;
4. Resting blood pressure less than 100/60 mmHg;
5. untreated pheochromocytoma;
6. untreated thyroid disease;
7. Patients on dihydropyridine or non-dihydropyridine calcium channel blockers (e.g., diltiazem, verapamil, nifedipine, amlodipine);
8. Severe peripheral vascular disease (intermittent claudication);
9. Patients on antiarrhythmic drugs (e.g., amiodarone, sotalol, digoxin);
10. Patients with renal insufficiency (defined as creatinine clearance greater than 0.15 mmol/L);
11. 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
12. Patients using colistin, digoxin, rizatriptan, cimetidine, hydralazine, guanethidine, or ergotamine.
13. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: propranolol (beta-blocker used treat high blood pressure)+surgeries

Drug: 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 surgery, patients continue propranolol for 3 weeks. Patients will be monitored daily for symptoms, blood pressure, and heart rate and will be followed for observation at 6, 12, and 24 months after surgery until disease progression or clinical death, unless intolerable toxicity occurs and the patient refuses to continue treatment. The efficacy and safety of the preoperative propranolol β-blockade regimen in patients with gastrointestinal tract tumors was evaluated using the study objectives in S

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anxiety Depression Scale Scores	Hamilton Anxiety Scale. The higher the score, the worse the symptoms.	Within two years of enrollment
heart rate	Sympathetic nervous system activation index	From enrollment to 24 days postoperatively
Heart rate variability	Sympathetic nervous system activation index	From enrollment to 24 days postoperatively
blood preasure	Sympathetic nervous system activation index	From enrollment to 24 days postoperatively
Norepinephrine levels	Sympathetic nervous system activation index	From enrollment to 24 days postoperatively
blood glucose	Sympathetic nervous system activation index	From enrollment to 24 days postoperatively
SaO2	Sympathetic nervous system activation index	From enrollment to 24 days postoperatively
RNA-seq of tumor tissue	Tumor tissues were examined by RNA-seq to assess the alteration of tumor microenvironment before and after treatment, and to explore the possible alteration of activation pathways (DAMP, RIG-I, NF-kB, JAK-STAT, etc.).	Baseline and during surgery
RNA-seq of peripheral blood PBMCs	Peripheral blood PBMCs were examined by RNA-seq to assess the alteration of tumor microenvironment before and after treatment, and to explore the possible alteration of activation pathways (DAMP, RIG-I, NF-kB, JAK-STAT, etc.).	Baseline and during surgery
Flow cytometry of peripheral blood PBMC	Flow cytometry was applied to the peripheral blood PBMC to assess the changes in the systemic immune system and tumor immune microenvironment before and after treatment, and to explore new subpopulations of immune cells with characteristic alterations.	Baseline and during surgery
Flow cytometry of tumor tissues	Flow cytometry was applied to the tumor tissues to assess the changes in the systemic immune system and tumor immune microenvironment before and after treatment, and to explore new subpopulations of immune cells with characteristic alterations.	Baseline and during surgery
ELISA detection of tumor tissue	Tumor tissues were examined using ELISA to explore functional changes in specific immune cell subsets before and after preoperative propranolol treatment.	Baseline and during surgery
ELISA detection of peripheral blood PBMCs	Functional changes in specific immune cell subsets before and after preoperative propranolol treatment were explored using ELISA for peripheral blood PBMC.	Baseline and during surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
2-year OS rate	Two years after surgery
2-year RFS rate	Two years after surgery

Collaborators and Investigators

• Sponsor: Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: December 27, 2024
• First Submitted That Met QC Criteria: January 9, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 9, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Anti-Arrhythmia Agents; Adrenergic Agents; Vasodilator Agents; Antihypertensive Agents; Adrenergic Antagonists; Adrenergic beta-Antagonists; Propranolol
• Other Study ID Numbers: KY2024-1317

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No