Clinical trial NCT06775080: The Use of Propranolol in the Perioperative Period of Resectable Gastrointestinal Tumors
Official title: The Use of Propranolol in the Perioperative Period of Resectable Gastrointestinal Tumors and the Study of Its Immune Mechanism Research
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Gastrointestinal Tumors
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2025-01-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Anxiety Depression Scale Scores
timeFrame: Within two years of enrollment
measure: heart rate
timeFrame: From enrollment to 24 days postoperatively
measure: Heart rate variability
timeFrame: From enrollment to 24 days postoperatively
measure: blood preasure
timeFrame: From enrollment to 24 days postoperatively
measure: Norepinephrine levels
timeFrame: From enrollment to 24 days postoperatively
measure: blood glucose
timeFrame: From enrollment to 24 days postoperatively
measure: SaO2
timeFrame: From enrollment to 24 days postoperatively
measure: RNA-seq of tumor tissue
timeFrame: Baseline and during surgery
measure: RNA-seq of peripheral blood PBMCs
timeFrame: Baseline and during surgery
measure: Flow cytometry of peripheral blood PBMC
timeFrame: Baseline and during surgery
measure: Flow cytometry of tumor tissues
timeFrame: Baseline and during surgery
measure: ELISA detection of tumor tissue
timeFrame: Baseline and during surgery
measure: ELISA detection of peripheral blood PBMCs
timeFrame: Baseline and during surgery
Secondary outcomes:
measure: 2-year OS rate
timeFrame: Two years after surgery
measure: 2-year RFS rate
timeFrame: Two years after surgery
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
state: Shanghai
Study officials:
References: