Importance of Surgical Approach for Gynecological Surgery on Metabolic Effects and Subsequent Recovery

Importance of Surgical Approach for Hysterectomies on Metabolic Effects Regarding Development of Insulin Resistance and Subsequent Recovery. A Randomized Controlled Study.

Insulin resistance is a key reaction to surgery and trauma and reflects the degree of metabolic stress. With greater degree of insulin resistance the development of complications increase, in particular infectious complications. The aim of this study is to determine if robotic assisted total laparoscopic hysterectomy induces less insulin resistance compared to abdominal hysterectomy. Insulin resistance is measured by the hyperinsulinemic normoglycemic clamp method. In addition inflammatory factors and clinical recovery will be measured.

Study Overview

• Status: Unknown
• Conditions: Insulin Resistance
• Intervention / Treatment: Procedure: Robot assisted laparoscopic hysterectomy; Procedure: Abdominal hysterectomy

Detailed Description

This is a prospective randomized controlled single center study. Primary screening will take place in the gynecological ward of Orebro University hospital according to the inclusion and exclusion criteria. 20 patients will be enrolled. All participants are randomized between robotic assisted total laparoscopic hysterectomy and total abdominal hysterectomy.

The main purpose of this study are to determine if robotic assisted laparoscopic hysterectomy induces less insulin resistance compare to abdominal hysterectomy. Both patients with benign and malignant disease are included. In addition inflammatory factors such as IL-6 and CRP are measured and clinical recovery is measured.

Each patient will be studied twice using the hyperinsulinemic normoglycemic clamp, a method that now is the gold standard for determining insulin sensitivity. During the clamp insulin is infused intravenously to attain an elevation at levels seen after an abnormal meal. At the same time glucose is infused to balance the effect of insulin and to maintain normal blood glucose level. The amount of the glucose infusion needed is the level of insulin sensitivity. The clamp procedure is performed before surgery as a control measure and the morning after surgery to yield the relative change in insulin sensitivity caused by the operation (postoperative insulin resistance). Before the onset of the infusion, and after 60 minutes of steady state during insulin stimulation, blood is collected for the analysis of immune function. This is also collected 3 hours after surgery.

A 6 minutes walk test is performed before surgery and the day after surgery, in order to determine a more clinical measure on recovery.

In addition demographic and clinical data are systematically collected during the hospital stay and 30 days after.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lena Wijk, MD; Phone Number: +46196022040; Email: lena.wijk@oru.se
• Study Contact Backup: Name: Kerstin Nilsson, MD, PhD; Phone Number: +46196022389; Email: kerstin.nilsson@orebroll.se

Study Locations

• Sweden
  • Örebro, Sweden
    • Recruiting
    • Örebro Univeristy Hospital
    • Contact: Lena Wijk, MD; Phone Number: +46196022040; Email: lena.wijk@oru.se
    • Contact: Kerstin Nilsson, MD, PhD; Phone Number: +46196022389; Email: kerstin.nilsson@orebroll.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Over 18 years of age
• Scheduled to total hysterectomy and/or bilateral salpingo-oophorectomy (BSOE).
• Both malignant or benign indications
• The operation should be technically possible to perform with laparoscopy or by abdominal incision, including approval from an anesthesiologist
• Acceptance to participate in the study and signed written informed consent document
• Proficiency in Swedish language

Exclusion Criteria:

• The operation is anticipated to comprise more than the hysterectomy + BSOE
• Diabetes mellitus
• Severe chronic pain or massive pain medication
• Severe inflammatory disease like active severe endometriosis or inflammatory bowel disease
• Known severe adhesions in the abdomen
• Contraindications on non steroidal analgesia
• Medication with drugs or disease affecting insulin resistance for example cortisone
• Mentally disabled women who cannot fill in the questionnaires or understand the consequences of participating in a trial
• Severe psychiatric disease or on medication for psychiatric disease so that the physician consider participation in the trial inappropriate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Robot assisted laparoscopic hysterectomy; Robot assisted laparoscopic total hysterectomy	Procedure: Robot assisted laparoscopic hysterectomy; Robotic assisted total laparoscopic hysterectomy.
Active Comparator: Abdominal hysterectomy; Standard extrafascial abdominal total hysterectomy through a low transverse abdominal wall incision.	Procedure: Abdominal hysterectomy; Standard extrafascial abdominal total hysterectomy through a low transverse abdominal wall incision.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin resistance	Insulin resistance is measured by the hyperinsulinemic normoglycemic clamp, a method that now is the golden standard for determining insulin sensitivity. The clamp is measured 1-2 weeks before surgery and on the morning after surgery.	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in biomarkers of inflammation and the immune system.	Biomarkers for example IL6 and CRP are measured. Biomarkers are measured two times during the hyperinsulinemic normoglycemic clamp before surgery, 3 hours after surgery and two times during the clamp after surgery.	3 weeks
6 minutes walk test	Measured before surgery and on the day after surgery 25-26 hours after surgery.	3 weeks
postoperative outcomes	Postoperative outcome is registered systematically according to the ERAS Society register.	4 weeks
complications	Adverse events are registered systematically from start of anesthesia to 30 days after surgery	4 weeks

Collaborators and Investigators

• Sponsor: Region Örebro County
• Investigators: Study Chair: Kerstin Nilsson, MD, PhD, Department of Obstetrics and Gynecology, Örebro University Hospital, School of medicine, Örebro University, Sweden; Principal Investigator: Lena Wijk, MD, Department of Obstetrics and Gynecology, Örebro University Hospital, School of Health and Medical Sciences, Örebro University, Sweden; Study Chair: Olle Ljungqvist, MD, Prof, Department of Surgery, Örebro University Hospital, School of Health and Medical Sciences Örebro University, Sweden.

Publications and helpful links

General Publications

• Wijk L, Nilsson K, Ljungqvist O. Metabolic and inflammatory responses and subsequent recovery in robotic versus abdominal hysterectomy: A randomised controlled study. Clin Nutr. 2018 Feb;37(1):99-106. doi: 10.1016/j.clnu.2016.12.015. Epub 2016 Dec 23.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): July 1, 2015
• Study Completion (Anticipated): July 1, 2015

Study Registration Dates

• First Submitted: November 11, 2014
• First Submitted That Met QC Criteria: November 13, 2014
• First Posted (Estimate): November 14, 2014

Study Record Updates

• Last Update Posted (Estimate): November 14, 2014
• Last Update Submitted That Met QC Criteria: November 13, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Insulin resistance; Metabolism; Hysterectomy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: OLL-431061