The Pathogenesis of Chronic Diarrhoea After Treatment for Cancer in Cecum and the Ascending Colon

Many patients suffer from chronic diarrhoea after surgical treatment for cancer in the right side of the colon.

The investigators' main hypothesis is that colon cancer patients with chronic diarrhoea have a higher risk of bile acid malabsorption compared with colon cancer patients without diarrhoea.

The investigators also expect that a part of the cases of bile acid malabsorption is caused by underlying bacterial overgrowth in the small bowel.

The investigators assume that patients with severe bile acid malabsorption have a lower value of FGF19 in the blood compared to patients with moderate or none bile acid malabsorption.

Furthermore, it is assumed that patients with chronic diarrhoea and documented bile acid malabsorption after surgical treatment for right-sided colon cancer will get improved bowel function when treated with a bile acid binder, or antibiotics in case of bacterial overgrowth.

Study Overview

• Status: Completed
• Conditions: Diarrhea; Colon Adenocarcinoma
• Intervention / Treatment: Drug: Antibiotics; Drug: Bile Acid Binder

Detailed Description

Patients with chronic diarrhoea after surgical treatment of right-sided colon cancer will be compared to patients without diarrhoea after right-sided colon cancer treatment.

All patients will be asked to answer a short questionnaire regarding bowel function, and they will all have standard blood tests taken to exclude non-cancer related causes of diarrhoea. Besides these standard tests, the value of FGF19 will be measured in a blood sample from the fasting participants. All participants will undergo SeHCAT scan to determine the presence of bile acid malabsorption among right-sided colon cancer patients with and without diarrhoea. In addition, a glucose breath test will be performed to examine, if the patients have small intestinal bacterial overgrowth.

Patients with a positive glucose breath test, and thus bacterial overgrowth, will be treated with antibiotics, followed by another SeHCAT scan, glucose breath test, and measurement of gastrointestinal transit time. In addition, they will be asked to complete the questionnaire regarding bowel function again. All cases with an abnormal SeHCAT scan will be treated with a bile acid binder, and the patients will be asked to complete the questionnaire one more time, and the GITT measurement will be repeated.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Department of Hepatology and Gastroenterology, Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary adenocarcinoma in cecum or the ascending colon
• Right-sided hemicolectomy
• Understanding, speaking and reading Danish

Exclusion Criteria:

• Previous major gastrointestinal, urological or gynaecological surgery or oncological treatment
• Radiation therapy
• Recurrence of colon cancer
• Metastasis
• Permanent stoma
• Pregnancy
• Reduced cognitive level that makes it plausible that the patient do not understand the study or is not capable of participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Positive breath test; Patients with a positive breath test are treated with antibiotics.	Drug: Antibiotics; Ciprofloxacin or Rifaximin for 10 days.
Active Comparator: Positive SeHCAT scan; Patients with a positive SeHCAT scan are treated with a bile acid binder.	Drug: Bile Acid Binder; Cholestyramine or Colesevelam lifelong.
No Intervention: No intervention; Patients with a normal breath test and a normal SeHCAT scan receive no intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in SeHCAT retention after 7 days.	The diagnosis of bile acid malabsorption in cases vs. controls is determined by a positive SeHCAT scan.	The SeHCAT scan consists of a baseline measurement and a measurement after 7 days.
Serum concentration of FGF19	The serum value of FGF19 is measured by a blood sample.	Through study completion, an average of 1 month.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of bacteria in the small bowel	The diagnosis of bacterial overgrowth in the small bowel is determined by a breath test.	Through study completion, an average of 1 month.
Symptom relief after treatment with antibiotics or bile acid binder	This will be estimated based on self-reported symptoms: A bowel function questionnaire with 30 questions regarding different aspects of bowel function. The patients should state if they have the symptoms daily, 1-6 times per week, less than once a week, or never.	After 3 months.
Quality of life after treatment with antibiotics or bile acid binder	This will be estimated based on self-reported symptoms: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 version 3.0. A questionnaire with 30 individual questions summing up to form one global health status, five functional subscales, three symptom scales and six single items addressing different aspects of quality of life. The scales range from 0-100 with a higher score representing a higher level of functioning or a higher degree of symptoms, respectively.	After 3 months.

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: GE Healthcare; Danish Cancer Society
• Investigators: Study Chair: Søren Laurberg, MD DMSc, Department of Surgery, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2017
• Primary Completion (Actual): May 26, 2021
• Study Completion (Actual): May 26, 2021

Study Registration Dates

• First Submitted: April 23, 2019
• First Submitted That Met QC Criteria: June 28, 2019
• First Posted (Actual): July 1, 2019

Study Record Updates

• Last Update Posted (Actual): September 8, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Small intestinal bacterial overgrowth; Bile acid malabsorption
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Bile Acids and Salts
• Other Study ID Numbers: 1-10-72-301-16; 1-16-02-137-17 (Other Identifier: Danish Data Protection Agency)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No