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

Phase 2

Recruiting

• Conditions: Gastrointestinal Tumors
• Interventions: Drug: propranolol (beta-blocker used treat high blood pressure)

• Registration Number: NCT06775080
• Lead Sponsor: Huashan Hospital

Brief Summary

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.

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 Timeline

• Status Verified: 2024-12
• Study Start: 2024-12-01
• Study First Submitted: 2024-12-27
• Study First Submitted QC: 2025-01-09
• Last Update Submitted: 2025-01-09
• Study First Posted: 2025-01-14
• Last Update Posted: 2025-01-14
• Primary Completion: 2026-12-31
• Study Completion: 2027-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
propranolol (beta-blocker used treat high blood pressure)+surgeries	propranolol (beta-blocker used treat high blood pressure)	-

Primary Outcome Measures

Name	Time	Method
heart rate	From enrollment to 24 days postoperatively	Sympathetic nervous system activation index
Heart rate variability	From enrollment to 24 days postoperatively	Sympathetic nervous system activation index
blood preasure	From enrollment to 24 days postoperatively	Sympathetic nervous system activation index
Norepinephrine levels	From enrollment to 24 days postoperatively	Sympathetic nervous system activation index
blood glucose	From enrollment to 24 days postoperatively	Sympathetic nervous system activation index
SaO2	From enrollment to 24 days postoperatively	Sympathetic nervous system activation index
Anxiety Depression Scale Scores	Within two years of enrollment	Hamilton Anxiety Scale. The higher the score, the worse the symptoms.
RNA-seq of tumor tissue	Baseline and during surgery	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.).
Flow cytometry of tumor tissues	Baseline and during surgery	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.
ELISA detection of tumor tissue	Baseline and during surgery	Tumor tissues were examined using ELISA to explore functional changes in specific immune cell subsets before and after preoperative propranolol treatment.
RNA-seq of peripheral blood PBMCs	Baseline and during surgery	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.).
Flow cytometry of peripheral blood PBMC	Baseline and during surgery	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.
ELISA detection of peripheral blood PBMCs	Baseline and during surgery	Functional changes in specific immune cell subsets before and after preoperative propranolol treatment were explored using ELISA for peripheral blood PBMC.

Secondary Outcome Measures

Name	Time	Method
2-year OS rate	Two years after surgery
2-year RFS rate	Two years after surgery

Trial Locations

Locations (1)

Huashan Hospital, Fudan University; 🇨🇳 Shanghai, Shanghai, China