COLONIC RESECTION FOR CANCER AS DIABETOGENIC RISK FACTOR

Surgery Clinical Trial

— COLECDIAB  

Official title:

COLONIC RESECTION FOR CANCER AS DIABETOGENIC RISK FACTOR - A Study of the Pathophysiological Effects of Colon Resection on Glucose Homeostasis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04649567
• Other study ID #: H-20015184
• Status: Recruiting
• Start date: October 10, 2020
• Est. completion date: August 31, 2023

Study information

• Verified date: November 2020
• Source: Hvidovre University Hospital
• Contact: Louise L Lehrskov, MD, PhD
• Phone: 0045 26817798
• Email: louise.lang.lehrskov.01[@]regionh.dk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Colon cancer (CC) survivors have an increased risk of developing T2D. A recent study revealed that the surgical procedures per se may be causally involved. Hence, left-sided colon resections increased the risk of developing T2D. In addition, treatment with chemotherapy may play a role in the pathogenesis. Given the steadily improving survival rate after a CC diagnosis, prevention of secondary diseases such as T2D is important to improve quality of life in these patients and to reduce socioeconomic expenses. This study aims to elucidate the effect of resection of tumors located in the left part of the colon on pathophysiological intermediates, which may lead to T2D 12 months post-surgery or later. The physiological mechanism might be a changed postprandial secretion of gut hormones including glucagon-like peptide-1 (GLP-1) secreted from L-cells in the left part of the colon. The investigators will evaluate changes in primarily glucose homeostasis as well as in gastrointestinal hormones, microbiota, visceral fat accumulation and markers of low-grade inflammation etc. in CC survivors who underwent a left hemicolectomy or sigmoidectomy.

Material and Methods: 60 patients will be included in this explorative clinical study. Patients will be divided into 4 groups depending on surgical procedure and treatment with chemotherapy. In the group of patients undergoing left hemicolectomy or sigmoidectomy ± treatment with chemotherapy 2 x 15 patients will be included, and in the group of patients scheduled to undergo right hemicolectomy ± treatment with chemotherapy another 2 x 15 patients will be included. During the 3 study visits (before surgery, 3-4 weeks post-surgery and 12 months post-surgery) the following tests will be performed: An oral glucose tolerance test, blood and fecal sampling, a DXA scan and an ad libitum meal test.

Implications: With this study the investigators expect to obtain an insight in the pathogenesis behind the possible development of T2D in CC survivors who underwent a resection of the left part of the colon ± treatment with chemotherapy. This insight may also help scientists develop new ways of treating or preventing T2D in general.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: August 31, 2023
• Est. primary completion date: August 31, 2023
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

Inclusion criteria:

• Adult (> 18 yrs.)

• ASA score 1-3

• Signed written informed consent

• Hba1c <48 mmol/mol

• Hemoglobin = 6,5 mmol/L

Exclusion Criteria:

• • Pregnancy

• Known type 1 or 2 diabetes

• Inflammatory bowel disease (Ulcerous colitis and Crohns' disease).

• Prior major abdominal surgery including bariatric surgery or colorectal resections

• Treatment with agents that may interfere with glucose homeostasis and or appetite or reduce the chance of successful follow-up examination

• Planned stoma

Related Conditions & MeSH terms

• Chemotherapy Effect
• Colon Cancer
• Glucose Metabolism Disorders
• Metabolic Diseases
• Surgery

Locations

Country	Name	City	State
Denmark	Rigshopitalet	Copenhagen	Please Select
Denmark	Hvidovre Hospital	Hvidovre

Sponsors (3)

Lead Sponsor	Collaborator
Hvidovre University Hospital	Herlev Hospital, Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	changes in GLP-1 (iAUC) to a 3-hour OGTT		3-4 weeks and 1 year after anticancer treatment
Other	changes in bacterial composition in fecal samples		3-4 weeks and 1 year after anticancer treatment
Other	changes in appetite during an ad libitum meal test by VAS scale (1-10). 10 represents highest value.		3-4 weeks and 1 year after anticancer treatment
Other	Changes in body weight		3-4 weeks and 1 year after anticancer treatment
Other	Changes in body composition (fat, bone and lean tissue) by DXA scan		3-4 weeks and 1 year after anticancer treatment
Other	changes in plasma concentration of leucocytes		3-4 weeks and 1 year after anticancer treatment
Other	changes in plasma concentration of neutrophils		3-4 weeks and 1 year after anticancer treatment
Other	changes in plasma concentration of hs-CRP		3-4 weeks and 1 year after anticancer treatment
Other	changes in plasma concentration of IL-6		3-4 weeks and 1 year after anticancer treatment
Other	changes in plasma concentration of soluble IL-6 receptor		3-4 weeks and 1 year after anticancer treatment
Other	changes in plasma concentration of IL-1Ra		3-4 weeks and 1 year after anticancer treatment
Other	changes in plasma concentration of INF-?		3-4 weeks and 1 year after anticancer treatment
Other	changes in plasma concentration of TNF-a		3-4 weeks and 1 year after anticancer treatment
Other	changes in plasma concentration of leptin		3-4 weeks and 1 year after anticancer treatment
Other	changes in plasma concentration of adiponectin		3-4 weeks and 1 year after anticancer treatment
Other	changes in plasma concentration of IL-10		3-4 weeks and 1 year after anticancer treatment
Other	changes in plasma concentration of IL-8		3-4 weeks and 1 year after anticancer treatment
Other	Changes in fasting plasma bile acids concentrations		3-4 weeks and 1 year after anticancer treatment
Other	Changes in gastric emptying rate by plasma paracetamol concentrations during a 3-hour OGTT		3-4 weeks and 1 year after anticancer treatment
Other	Changes in systemic lipid concentration by fasting plasma triglycerides, HDL and LDL cholesterol		3-4 weeks and 1 year after anticancer treatment
Other	Changes in unbiased mass-spectrometry (plasma proteomics that captures over 400 circulating proteins in blood including markers of low-grade inflammation and lipid metabolism)		3-4 weeks and 1 year after anticancer treatment
Other	changes in the metabolome (concentrations of aminoacids) in plasma samples		3-4 weeks and 1 year after anticancer treatment
Other	changes in the metabolome (concentrations of bile acids) in plasma samples		3-4 weeks and 1 year after anticancer treatment
Other	changes in the metabolome (concentrations lipids) in plasma samples		3-4 weeks and 1 year after anticancer treatment
Other	Changes in gene Risk Score for T2D by analysing buffy coat suspension		3-4 weeks and 1 year after anticancer treatment
Other	Changes in quality of life measured by the questionnaire Functional Assessment of Cancer Therapy (FACT-C)		3-4 weeks and 1 year after anticancer treatment
Other	Changes in insulin secretion rate (ISR) by an OGTT		3-4 weeks and 1 year after anticancer treatment
Other	Changes in insulinogenic index (IGI) by an OGTT		3-4 weeks and 1 year after anticancer treatment
Other	Changes in ß-cell glucose sensitivity (ß-GS) by an OGTT		3-4 weeks and 1 year after anticancer treatment
Other	Changes in insulin resistance by HOMA analysis (HOMA-IR) by an OGTT		3-4 weeks and 1 year after anticancer treatment
Other	Changes in disposition index by an OGTT		3-4 weeks and 1 year after anticancer treatment
Other	Changes in insulin clearance by an OGTT		3-4 weeks and 1 year after anticancer treatment
Other	Changes in rates of absorption of the ingested glucose by an OGTT		3-4 weeks and 1 year after anticancer treatment
Other	Change in physical activity level measured by International Physical Activity Questionnaires (IPAQ) questionnaire		1 year after anticancer treatment
Other	Changes in PYY (iAUC) response to a 3-hour OGTT		3-4 weeks and 1 year after anticancer treatment
Other	Changes in GLP-2 (iAUC) in responses to a 3-hour OGTT		3-4 weeks and 1 year after anticancer treatment
Other	Changes in GIP (iAUC) in responses to a 3-hour OGTT		3-4 weeks and 1 year after anticancer treatment
Other	changes in ghrelin (iAUC) in responses to a 3-hour OGTT		3-4 weeks and 1 year after anticancer treatment
Other	Changes in CCK (iAUC) in responses to a 3-hour OGTT		3-4 weeks and 1 year after anticancer treatment
Other	changes in OXM (iAUC) in responses to a 3-hour OGTT		3-4 weeks and 1 year after anticancer treatment
Other	Changes in neurotensin (iAUC) in responses to a 3-hour OGTT		3-4 weeks and 1 year after anticancer treatment
Other	Changes in glicentin (iAUC) in responses to a 3-hour OGTT		3-4 weeks and 1 year after anticancer treatment
Other	Changes in gene risk Score for T2D using buffy coat analysis		3-4 weeks and 1 year after anticancer treatment
Primary	Changes in 2-hour blood glucose (OGTT) 12 months after hemicolectomy ± chemotherapy		3-4 weeks and 1 year after anticancer treatment
Secondary	Changes in blood glucose (iAUC) and (tAUC) in response to a 3-hour OGTT		3-4 weeks and 1 year after anticancer treatment
Secondary	Changes in hemoglobin a1c (HbA1c)		3-4 weeks and 1 year after anticancer treatment
Secondary	Changes in fasting blood glucose levels (mmol/L)		3-4 weeks and 1 year after anticancer treatment