Clinical trial NCT04649567: COLONIC RESECTION FOR CANCER AS DIABETOGENIC RISK FACTOR
Official title: COLONIC RESECTION FOR CANCER AS DIABETOGENIC RISK FACTOR - A Study of the Pathophysiological Effects of Colon Resection on Glucose Homeostasis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Glucose Metabolism Disorders
Colon Cancer
Surgery
Chemotherapy Effect
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
Collaborators: name: Herlev Hospital
name: Rigshospitalet, Denmark
First posted: 2020-12-02
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 60 patients diagnosed with colon cancer will be investigated. They have to be planned for surgical resection of a segment of colon (left hemicolectomy, sigmoidectomy or right hemicolectomy) for cancer without signs of metastases (cT1-4N0-2M0), with and without planned treatment with adjuvant chemotherapy

Brief 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.


Eligibility criteria: 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

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