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

NCT06775080 | Recruiting Phase 2

• 1 other identifier: KY2024-1317
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastrointestinal Tumors

Outcome Measures

Primary Outcomes (13)

• 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 Outcomes (2)

• 2-year OS rate

  Two years after surgery

• 2-year RFS rate

  Two years after surgery

Study Arms (1)

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

EXPERIMENTAL

Drug: propranolol (beta-blocker used treat high blood pressure)

Interventions

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

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \) 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.

Sponsors & Collaborators

• Huashan Hospital: lead

Study Sites (1)

Huashan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200040, China

RECRUITING

MeSH Terms

Conditions

Digestive System Neoplasms

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: December 27, 2024
• First Posted: January 14, 2025
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: January 14, 2025

Record last verified: 2024-12

Locations

CN (1)