Attenuating The Post-Operative Insulin Resistance And Promoting Protein Anabolism

McGill University

Status: Terminated

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

Treatments: Drug: Placebo; Drug: Metformin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02393573

14-264-SDR

Details and patient eligibility

About

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.

Enrollment: 7 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

1. Already diagnosed with diabetes (Hb A1c > 6.5%)
2. Are pre-diabetic receiving glucose lowering intervention ( any glucose lowering medication)
3. Have renal or liver dysfunction (serum creatinine above 124 micromol/L in women and 133 micromol/L in men, bilirubin >50 micromol/L)
4. will undergo extended resection of adjacent organs, chest wall resections, bronchoplasty, non-anatomic lung resections
5. Will undergo Pneumonectomy
6. Non-elective operations
7. Have mental conditions (e.g. dementia, disabling orthopedic and neuromuscular disease, psychosis),
8. 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)
9. Have received steroids for longer than 30 days
10. Have poor English or French comprehension.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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7 participants in 2 patient groups, including a placebo group

Metformin

Active Comparator group

Description:

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.

Treatment:

Drug: Metformin

Placebo

Placebo Comparator group

Description:

Placebo will be administered exactly in the similar way to Metformin

Treatment:

Drug: Placebo