Clinical trial NCT04089813: Effect of Metformin on Chronic Pain After Thoracic Surgery in Diabetic Patients
Official title: Effect of Metformin on Chronic Pain After Thoracic Surgery in Diabetic Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Postoperative Chronic Pain
Lead sponsor: Xuzhou Medical University
Sponsor class: OTHER
First posted: 2019-09-13
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 200 diabetic patients undergoing elective thoracoscopic lobectomy in the Affiliated Hospital of Xuzhou Medical University.

Brief summary: Metformin has been found to have more and more functions as a commonly used hypoglycemic drug in clinic. It has been found that metformin has anti-inflammatory, anti-tumor and lipid metabolism regulating effects. Basic studies have shown that metformin as an adjuvant drug combined with gabapentin and tramadol is safe and effective in patients with neuropathic pain. Postoperative chronic pain as a common complication has seriously affected the quality of life and mood of patients after surgery.Some studies have shown that chronic pain after partial operation manifests as neuropathic pain. The effect of metformin on chronic pain after thoracic surgery in patients with diabetes mellitus was observed in this experiment, which was compared with patients taking insulin to control blood sugar.

Detailed description: The analgesic mechanism of metformin may include the following aspects:(1)Metformin relieves neuropathic pain mainly because it can activate adenosine monophosphate-activated protein kinase (AMPK), which plays a crucial role in pain regulation as an important endogenous kinase controlling energy metabolism.(2)In addition, metformin can also inhibit ERK signaling pathway, further inhibit sodium channel, prevent the development of peripheral sensitization and achieve the effect of relieving neuropathic pain. (3)Metformin has been shown to alleviate bone cancer pain in rats by reducing STAT3 phosphorylation.Clinical research in this field is limited to basic research and ethical requirements are rarely reported at home and abroad. Li Chunye et al. of Jiangsu University designed a clinical trial to compare the efficacy of metformin and gabapentin combined with tramadol on neuropathic pain. The results showed that metformin had a better effect.

The incidence of chronic pain after thoracic surgery is higher. Postoperative chronic pain is a complex pain. The nature and mechanism of chronic pain after thoracic surgery are still controversial. Some studies have shown that some chronic pain after thoracic surgery manifests neuropathic pain, the mechanism may be related to surgical incision, nerve injury caused by trauma and increased pain sensitization. Can metformin alleviate chronic pain after surgery? The research on this aspect is still blank at present.This study was designed as a prospective cohort study to observe whether there was a difference in the incidence of chronic pain after thoracoscopic lobectomy between patients taking metformin and patients injecting insulin to control blood sugar.

Eligibility criteria: Inclusion Criteria:

1. Aged between 18 and 70
2. Diabetes history. Use metformin or insulin to control blood sugar
3. The type of operation is selective thoracoscopic lobectomy.

Exclusion Criteria:

1. Newly diagnosed diabetic patients at admission
2. Complication of severe cardiopulmonary diseases
3. Refuse to participate in this experiment
4. Participate in other trials
5. Patients with diabetic complications (including diabetic nephropathy, peripheral neuropathy, etc.)

Primary outcomes:
measure: Incidence of chronic pain after operation
timeFrame: 3 months after operation
Secondary outcomes:
measure: VAS score at extubation time, 12 hours and 24 hours after operation
timeFrame: extubation time, 12 hours and 24 hours after operation
measure: Neuropathic pain score and incidence at 3 months after operation
timeFrame: 3 months after operation
measure: Anxiety and Depression Score
timeFrame: 3 months after operation
measure: Length of ICU stay
timeFrame: an average of 2 days
measure: Length of hospital stay
timeFrame: an average of 10 days
Other outcomes:
Locations:
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
Study officials:
affiliation: Afliated Hospital of Xuzhou Medical University
name: JinDong Liu, M.S
role: STUDY_DIRECTOR
References:
citation: Shiers S, Pradhan G, Mwirigi J, Mejia G, Ahmad A, Kroener S, Price T. Neuropathic Pain Creates an Enduring Prefrontal Cortex Dysfunction Corrected by the Type II Diabetic Drug Metformin But Not by Gabapentin. J Neurosci. 2018 Aug 15;38(33):7337-7350. doi: 10.1523/JNEUROSCI.0713-18.2018. Epub 2018 Jul 20.
citation: Pecikoza UB, Tomic MA, Micov AM, Stepanovic-Petrovic RM. Metformin Synergizes With Conventional and Adjuvant Analgesic Drugs to Reduce Inflammatory Hyperalgesia in Rats. Anesth Analg. 2017 Apr;124(4):1317-1329. doi: 10.1213/ANE.0000000000001561.
citation: Smith B, Ang D. Metformin: Potential analgesic? Pain Med. 2015 Dec;16(12):2256-60. doi: 10.1111/pme.12816. Epub 2015 May 29.
citation: Ge A, Wang S, Miao B, Yan M. Effects of metformin on the expression of AMPK and STAT3 in the spinal dorsal horn of rats with neuropathic pain. Mol Med Rep. 2018 Apr;17(4):5229-5237. doi: 10.3892/mmr.2018.8541. Epub 2018 Feb 1.