Attenuating The Post-Operative Insulin Resistance And Promoting Protein Anabolism

NCT02393573 | Terminated

• 1 other identifier: 14-264-SDR
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Major surgery results in a stress- induced catabolic response, marked by post-operative insulin resistance, hyperglycemia and loss of body protein, which is associated with increased morbidity, mortality and adverse outcomes. There has been a great deal of research on different approaches to optimize post-operative insulin sensitivity including hormonal and nutritional interventions, minimally invasive surgical techniques and epidural anesthesia. However, the correlation between insulin resistance and body protein loss is not well understood. Metformin is the most widely used insulin sensitizing and blood glucose-lowering drug in treatment of type 2 diabetic patients. This study will: 1) estimate the correlation between insulin resistance and body protein loss in pre-diabetic lung/colorectal resection patients; 2) investigate whether the post-operative metabolic state can be improved by the pre-operative administration of metformin; and assess the impact of metformin on surgical complications and hospital length of stay. The results of this study will provide insight into the relationship between insulin resistance and post-operative adverse events and potentially suggest a novel approach to improve outcomes using Metformin, a drug already in wide clinical use.

Conditions

Pre-Diabetes; Major Lung or Abdominal Surgery; Insulin Resistance

Keywords

Insulin Resistance; Protein balance; Surgery; Post operative complications; metformin; Pre-diabetes; Fasting blood glucose

Outcome Measures

Primary Outcomes (1)

• Change in fasting blood glucose

  the level of plasma glucose after 6 hours of fasting

  2 weeks before surgery (pre-operative) and on the morning before the surgery and every morning after the surgery (post operative) for three days or until discharge which ever comes earlier

Secondary Outcomes (6)

• Change in whole body protein balance

  2 weeks before surgery (pre-operative) and hours after the surgery (post operative)

• Comparing the Homeostasis model assessment (HOMA) index at three different time points ( by employing Fasting blood sugar and Plasma Insulin)

  at 3 time points as follow : 2 weeks before surgery, on the day of surgery and 48 hours after the surgery

• glycosylated Hba1c

  2 weeks before surgery

• Comparing the pre-operative body impedance and the post operative body impedance (to asses the body composition specifically the amount of body fat)

  2 weeks before surgery and 48 hours after the surgery

• Surgical Complications

  30 days after operation

Study Arms (2)

Metformin

ACTIVE COMPARATOR

Metformin will be administered as pills to be taken orally with an initial dose of 850 mg on the first day; the dose will be increased to 850 mg every 12 hours and 850mg every 8 hours respectively on the second day and then on the days to follow up to the morning of the surgery. Metformin will be discontinued on the day of surgery and will be restarted immediately after surgery.

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Placebo will be administered exactly in the similar way to Metformin

Drug: Placebo

Interventions

Metformin DRUG

Patients will take metformin for two weeks before Surgery and 2 days after the surgery

Metformin

Placebo DRUG

Patients will take Placebo pills for two weeks before Surgery and 2 days after the surgery

Placebo

Eligibility Criteria

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

You may qualify if:

• Elective open anatomic lung resections: segmentectomy, lobectomy, bi-lobectomy
• Colorectal surgery for non-metastatic disease (including right, transverse, left, sigmoid, subtotal, total, and hemicolectomy)
• Primary or secondary lung cancer
• At least 18 years of age with
• HbA1c 5.7- 6.5 %
• Not receiving any kind of glucose lowering medication.

You may not qualify if:

• Already diagnosed with diabetes (Hb A1c \> 6.5%)
• Are pre-diabetic receiving glucose lowering intervention ( any glucose lowering medication)
• Have renal or liver dysfunction (serum creatinine above 124 micromol/L in women and 133 micromol/L in men, bilirubin \>50 micromol/L)
• will undergo extended resection of adjacent organs, chest wall resections, bronchoplasty, non-anatomic lung resections
• Will undergo Pneumonectomy
• Non-elective operations
• Have mental conditions (e.g. dementia, disabling orthopedic and neuromuscular disease, psychosis),
• Have cardiac abnormalities, severe end-organ disease such as cardiac failure (New York Heart Association classes III-IV), Chronic obstructive pulmonary disease(COPD), sepsis, morbid obesity (BMI \>40 kg/m2), anemia (hematocrit \< 30 %, hemoglobin \<100g/L albumin \< 25mg/dl)
• Have received steroids for longer than 30 days
• Have poor English or French comprehension.

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead
• Mitacs: collaborator
• Medtronic - MITG: collaborator

Study Sites (1)

Montreal General Hospital

Montreal, Quebec, H3G 1A4, Canada

Location

MeSH Terms

Conditions

Glucose Intolerance; Insulin Resistance

Interventions

Metformin

Condition Hierarchy (Ancestors)

Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Liane Feldman, MD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

• Francesco Carli, MD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 10, 2015
• First Posted: March 19, 2015
• Study Start: November 1, 2015
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: March 23, 2018

Record last verified: 2018-03

Locations

CA (1)