Effect of COX-2 Selective Inhibitors on Postoperative Insulin Resistance After Gastrointestinal Laparoscopic Surgery

Effect of COX-2 Selective Inhibitors on Postoperative Insulin Resistance, Tramadol PCA and Early Postoperative Enteral Nutrition in Patients After Gastrointestinal Laparoscopic Surgery

It is well established that the resistance to the effects of insulin on glucose metabolism develops with a lot of stress hormone release after surgical trauma. This condition is known as insulin resistance (IR) characterized by hyperglycemia, hyperinsulinemia and lactic acidosis. Surgical IR not only affect glucose metabolism but also influence protein synthesis, then further exacerbate the depletion of the carbohydrate, fat and protein.

Postoperative pain is a challenging task for patients and surgeons, and it is part of the stress response to trauma and surgery, while the fear of pain can exacerbate the stress response.

The main aim of this study was to invest whether effective postoperative analgesia can reduce the stress response and insulin resistance.

Study Overview

• Status: Unknown
• Conditions: Gastrointestinal Cancer
• Intervention / Treatment: Drug: parecoxib

• Study Type: Interventional
• Enrollment (Anticipated): 164
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Wengcheng Kong, MD; Phone Number: 15850722032; Email: wenchengkong@gmail.com
• Study Contact Backup: Name: Yousheng Li; Phone Number: 8602580860137; Email: liys@medmail.com.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 200002
      • Recruiting
      • Jinling Hospital
      • Contact: Wencheng Kong, MD; Phone Number: 15850722032; Email: wenchengkong@gmail.com
      • Contact: Yousheng Li, MD; Email: liys@medmail.com.cn
      • Principal Investigator: Wencheng Kong, MD
      • Sub-Investigator: Danhua Yao, MD
      • Sub-Investigator: lele Ren, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Patients with gastrointestinal cancer scheduled for gastrointestinal laparoscopic surgery
• Patients between the ages of 18 and 70 yr
• ASA physical status I-II
• Requirements of informed consent and assent of participant, parent or legal guardian as applicable
• Consciousness and ability to cooperate

Exclusion criteria：

• History of alcohol, analgesic, or narcotic abuse
• Used analgesics, neuroleptics, antipsychotic agents, or corticosteroids within 6 hours of surgery
• A clinically significant laboratory abnormality or a history of significant cardiac, pulmonary, hepatic, or renal disease
• Female with positive pregnancy
• Allergy to conventional NSAIDs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: PCA,Placebo,Placebo; PCA for 2 days after operation, i.v placebo in 2 days after surgery and oral placebo in the day 3 to day 5 after surgery
Placebo Comparator: PCA,placebo,tramadol; PCA for 2 days after operation, i.v placebo in 2 days after surgery, and oral tramadol in the day 3 to day 5 after surgery
Experimental: PCA,parecoxib,placebo; PCA for 2 days after operation, i.v parecoxib in 2 days after surgery,and oral placebo in the day 3 to day 5 after surgery	Drug: parecoxib; 4 groups: PCA,Placebo,Placebo-PCA for 2 days after operation, i.v placebo in 2 days after surgery and oral placebo in the day 3 to day 5 after surgery; PCA,placebo,tramadol-PCA for 2 days after operation, i.v placebo in 2 days after surgery, and oral tramadol(0.1g t.i.d.) in the day 3 to day 5 after surgery;PCA,parecoxib,placebo-PCA for 2 days after operation, i.v parecoxib(40mg b.i.d.) in 2 days after surgery,and oral placebo in the day 3 to day 5 after surgery;PCA,parecoxib,celecoxib-PCA for 2 days after operation,i.v parecoxib(40mg b.i.d.) in 2 days after surgery and oral celecoxib(0.2g b.i.d.) in the day 3 to day 5 after surgery; Other Names: COX-2 selective inhibitors
Experimental: PCA,parecoxib,celecoxib; PCA for 2 days after operation,i.v parecoxib in 2 days after surgery and oral celecoxib in the day 3 to day 5 after surgery	Drug: parecoxib; 4 groups: PCA,Placebo,Placebo-PCA for 2 days after operation, i.v placebo in 2 days after surgery and oral placebo in the day 3 to day 5 after surgery; PCA,placebo,tramadol-PCA for 2 days after operation, i.v placebo in 2 days after surgery, and oral tramadol(0.1g t.i.d.) in the day 3 to day 5 after surgery;PCA,parecoxib,placebo-PCA for 2 days after operation, i.v parecoxib(40mg b.i.d.) in 2 days after surgery,and oral placebo in the day 3 to day 5 after surgery;PCA,parecoxib,celecoxib-PCA for 2 days after operation,i.v parecoxib(40mg b.i.d.) in 2 days after surgery and oral celecoxib(0.2g b.i.d.) in the day 3 to day 5 after surgery; Other Names: COX-2 selective inhibitors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Insulin resistance in perioperative period of gastrointestinal laparoscopic surgery	5 days after operation

Secondary Outcome Measures

Outcome Measure	Time Frame
The consumption of total and incremental tramadol after surgery.	5 days after operation
The tolerated dose of enteral nutrition every day after surgery	5 days after operation
Postoperative inflammatory factors (IL-4, IL-6 and TNF-α) and levels of stress hormone (glucocorticoids and catecholamines) in perioperative period of gastrointestinal laparoscopic surgery	5 days after operation
Rest energy metabolism was measured in perioperative period to evaluate the caloric and substrate needs of our patients	5 days after operation
The time of the first bowel movements and anal exhaust time after surgery	5 days after operation or more
Pain intensity at rest and during leg raising recorded daily after surgery using Visible Numeric Rating Scale	5 days after operation
Incidence of adverse events throughout the treatment period including nausea, vomiting, headache, urinary retention, somnolence, flatulence, and pruritus	5 days after operation or more
Liver and renal function tests in perioperative period	5 days after operation
Self-rating anxiety scale and self-rating questionnaire for depression before surgery	1 day before surgery

Collaborators and Investigators

• Sponsor: Jinling Hospital, China
• Collaborators: National Natural Science Foundation of China
• Investigators: Principal Investigator: Wencheng Kong, MD, Nanjing University

Publications and helpful links

General Publications

• Xu Z, Li Y, Wang J, Li J. Effect of postoperative analgesia on energy metabolism and role of cyclooxygenase-2 inhibitors for postoperative pain management after abdominal surgery in adults. Clin J Pain. 2013 Jul;29(7):570-6. doi: 10.1097/AJP.0b013e318270f97b.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Anticipated): August 1, 2015
• Study Completion (Anticipated): September 1, 2015

Study Registration Dates

• First Submitted: August 25, 2013
• First Submitted That Met QC Criteria: August 27, 2013
• First Posted (Estimate): August 28, 2013

Study Record Updates

• Last Update Posted (Estimate): November 10, 2014
• Last Update Submitted That Met QC Criteria: November 7, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Gastrointestinal Diseases; Hyperinsulinism; Insulin Resistance; Gastrointestinal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Parecoxib
• Other Study ID Numbers: PTP-IR-EEN-1