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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| propranolol (beta-blocker used treat high blood pressure)+surgeries | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| propranolol (beta-blocker used treat high blood pressure) | Drug | 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 |
| 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.). |
| Measure | Description | Time Frame |
|---|---|---|
| 2-year OS rate | Two years after surgery | |
| 2-year RFS rate | Two years after surgery |
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Inclusion Criteria:
Exclusion Criteria:
1) Pregnant or breastfeeding women, or women with pregnancy plans within six months; 2) Patients with absolute or relative contraindications to propranolol:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Huashan Hospital, Fudan University | Recruiting | Shanghai | Shanghai Municipality | 200040 | China |
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| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D011433 | Propranolol |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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|
| 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 |
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |