Condition category
Surgery
Date applied
05/02/2013
Date assigned
21/03/2013
Last edited
08/08/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Familial adenomatous polyposis (FAP) is an inherited condition which mainly affects the large intestine (also known as the large bowel or colon and rectum). People with FAP develop many polyps (which are like small cherries on stalks) inside their large bowel. There are many different types of polyps but these particular polyps are called adenomas (the "adenomatous" in FAP). An adenoma can in time turn into a cancer which is why prophylactic surgery is offered. Patients with FAP undergo prophylactic removal of the colon usually in their late teens, to prevent the development of colorectal cancer. Until recently it was thought that the only effect of removing the colon (most of the large bowel) was loose faeces. There is now some evidence that this surgery has more profound effects, including alteration in the way the body handles water, electrolytes, glucose and fats. While preliminary animal work has been done, the metabolic disturbances caused by removal of colon have not yet been demonstrated in humans after ileo-rectal anastomosis (IRA - joining the last part of the small bowel to the last part of the large bowel) or restorative proctocolectomy (RPC - removal of whole of the large bowel and rectum and joining the last part of the small bowel to the last part of the gut), which are two most common forms of surgery involving removal of the colon in patients with FAP. This study aims to identify whether there is a disturbance of glucose, water and electrolyte metabolism in patients with no colon, and to see whether that can be easily corrected by taking a water and salt mixture (rehydration solution).

Who can participate?
Patients with FAP after colectomy (and those with intact colon for part 3 of the study).

What does the study involve?
The study will be conducted in three stages at different time points.

Part 1 of the study aims to identify whether there is a disturbance of water, electrolyte and glucose metabolism in patients with no colon. The study involves no invasive investigations other than blood tests. Participant's blood samples will be collected in the outpatient clinic after an overnight fast (12 hours of fasting). Participants will be allowed to drink water, but will be asked to avoid sugary drinks. The participant will also provide a urine sample. The participant's blood pressure, body weight, height and test of muscle strength will be recorded non-invasively. The participant will be instructed to complete a 7-day food record for the assessment of both salt, energy and nutrient intakes prior to attending the clinical investigation day. Quality of life or self-reported health status will also be assessed using questionnaires.

Part 2 of the study aims to determine whether the disturbance in metabolism can be easily corrected by taking a rehydration solution. Participants will be randomly allocated to one of two groups. One group will receive a dummy (placebo) drink for 4 weeks, then after a 4-week break they will be provided with the active rehydration drink to be consumed with meals every day for 4 weeks. The other group will receive the active rehydration drink for 4 weeks, followed by a 4-week break, then they will receive the placebo drink for 4 weeks.

Part 3 of the study aims to see whether taking the rehydration solution immediately after the removal of the colon can be used to prevent the problem altogether. Patients will be randomly allocated to receive either the placebo drink or the active rehydration drink immediately after the removal of the colon.

Following discharge from the study, patients will have a consultation and will be given individual dietary advice based on their dietary record. They will also be advised to continue with the rehydration solution.

What are the possible benefits and risks of participating?
If we prove that the resection of the colon leads to disturbances in the water, electrolyte balance, sugar and fat metabolism, irrespective of underlying disease state, then rehydration therapy to restore sodium and fluid balance to normal control levels could form a simple, effective and cost-effective strategy to correct these disturbances. Participants will receive the routine post-operative follow-up as an out-patient. In addition to the routine follow-up tests, the only burden to the participant will be the time spent being told about the research project and thinking about whether they wish to participate. Upon obtaining consent, the other burden will be the time spent to complete the quality of life questionnaire, the time spent in giving information about their dietary habits, and providing additional blood and urine samples for analyses. By taking part in this study there are no risks of physical injury or harm. All the necessary information will be given and the blood tests will be performed where possible at an existing out-patient appointment to reduce the burden and to avoid unnecessary inconvenience to the participant.

Where is the study run from?
St Mark's Hospital, Harrow, UK.

When is the study starting and how long is it expected to run for?
The study started in December 2011 and is expected to end in December 2014.

Who is funding the study?
1. Royal College of Surgeons/Norman Williams IA Research Fellowship.
2. St Mark’s Hospital Foundation Seedcorn Fund.

Who is the main contact?
Miss Sue K Clark
s.clark8@nhs.net

Trial website

Contact information

Type

Scientific

Primary contact

Miss Susan Clark

ORCID ID

Contact details

Consultant Colorectal Surgeon
Assistant Director
The Polyposis Registry
St Mark's Hospital
Harrow
HA1 3UJ
United Kingdom
+44 (0)20 8235 4018
s.clark8@nhs.net

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Metabolic consequences following colectomy

Acronym

Study hypothesis

Colon (large bowel) is an active metabolic organ, removal of which leads to adaptation of other tissues in the body. Until recently it was thought that the only effect of removing the colon (most of large bowel) was loose faeces. There is now some preliminary evidence that this surgery has more profound effects, including alteration in the way the body handles water, electrolytes, glucose and fats. Disturbance of this control by the body can lead to serious metabolic disturbances and poor quality of life.

Ethics approval

NRES Committee London-Stanmore, 16/08/2011, ref: 11/LO/1014

Study design

Part 1 - Prospective observational study
Parts 2 and 3 - Prospective randomised controlled trials

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Quality of life

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Metabolic disturbances following colectomy

Intervention

Part 1 (Observational study)
Experimental design: To measure indices of sodium intake (diet diary), sodium loss (urine Na+, K+, plasma aldosterone) and insulin resistance (insulin, glucose, adiponectin, fasting lipids and blood pressure) in a large cohort of patients.
Methods: 50 IRA, 25 RPC and 25 colectomy with ileostomy patients will be recruited. Patients will attend one clinical investigation day. As part of the clinical investigation day, participant's blood samples will be collected in the outpatient clinic after an overnight fast (12 hours of fasting). Participant will be allowed to drink water, but will be asked to avoid sugary drinks. The participant will also provide a urine sample to be tested. The participant's blood pressure, body weight, height and test of muscle strength will be recorded non-invasively. The participant will be instructed to complete a 7 day food record for the assessment of both salt, energy and nutrient intakes prior to attending the clinical investigation day. Quality of life, or self-reported health status will also be assessed using the SF-36 and FACIT (F)–version-4 questionnaires and compared to reference values from the general population.

Part 2
Experimental design: To perform a single-blind, placebo-controlled randomised cross-over trial of the effects of rehydration on the hyperaldosteronism and abnormal glucose tolerance in patients after IRA or RPC or colectomy with ileostomy.
Methods: 30 patients with demonstrated hyperaldosteronism from part 1 will be recruited.
Arm A: 15 patients will receive the 'placebo' drink for 4 weeks. Patients will then attend a clinical investigation day as for part 1 of the study. Patients will then have a 4-week washout period following which they will attend St Mark's Hospital for their second clinical investigation day. Patients will be provided with the active rehydration drink sachets (1 sachet in 1 litre of water to be consumed 1 tumbler with meals everyday). Patients will be advised to consume the active rehydration drink for 4 weeks following which they will attend St Mark's Hospital for their third clinical investigation day.
Arm B : As above, but 15 patients will receive the active rehydration drink for 4 weeks, followed by a 4 week washout period and will then receive the 'placebo' drink for 4 weeks. Patients will attend St Mark's Hospital for clinical investigation days as above.

Part 3
Experimental design: To perform a single-blind, placebo-controlled randomised trial of the effects of rehydration on the hyperaldosteronism and abnormal glucose tolerance in patients after IRA.
Methods: 20 patients scheduled for IRA will be recruited.
Following recruitment, patients will attend St Mark's Hospital for a pre-operative clinical investigation day as described in part 1 and 2 of the study. Patients will be randomised to receive either the 'placebo' drink (as in part 2) or the active rehydration drink (as in part 2) starting from the immediate post-operative period.
Arm A: 10 patients will receive 'placebo' drink. Arm B: 10 patients will receive active rehydration drink.
Patients will attend St Mark's Hospital for clinical investigative day at 3, 6 and 12 months post surgery.

Intervention type

Procedure/Surgery

Phase

Not Applicable

Drug names

Primary outcome measures

To determine how prevalent sodium depletion and hyperaldosteronism are in well adapted patients following ileorectal anastomosis (IRA) or restorative proctocolectomy (RPC) or colectomy with ileostomy.

Secondary outcome measures

1. To determine if sodium depletion in well adapted patients following IRA or RPC or colectomy with ileostomy is associated with and causative of abnormal glucose tolerance.
2. To ascertain if we can we reverse these metabolic changes with a simple rehydration therapy which could be easily incorporated into patient aftercare.
3. To ascertain if we can prevent these metabolic changes developing post-operatively with a simple rehydration therapy which could be easily incorporated
4. Differences in health-related quality of life scores as assessed using SF-36 and FACIT- F questionnaires

Overall trial start date

05/12/2011

Overall trial end date

31/12/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Participants who have undergone IRA or RPC or colectomy with ileostomy
2. Surgery >1 year previously, or preoperative patients (part 3)
3. Absence of small bowel disease; Crohn's, Coeliac disease etc
4. No recent use of steroid medication (< 1 year)
5. 18 < BMI < 30 kg/m2
6. Minimal small bowel resection (<10 cm)
7. Aged 14-70 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

150

Participant exclusion criteria

1. Patients with diabetes
2. Patients who are unwilling to consent
3. Patients who are regularly taking the electrolyte mix
4. Patients with any known adrenal gland disorder

Recruitment start date

05/12/2011

Recruitment end date

31/12/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Consultant Colorectal Surgeon
Harrow
HA1 3UJ
United Kingdom

Sponsor information

Organisation

North West London Hospitals NHS Trust (UK)

Sponsor details

Department of Research and Development
c/o Simon Lewis
Watford Road
Harrow
HA1 3UJ
United Kingdom
+44 (0)20 8869 2011
simon.lewis4@nhs.net

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Research organisation

Funder name

Royal College of Surgeons/Norman Williams IA Research Fellowship granted in July 2012. The applicant’s (Miss S Mallappa) clinical salary is covered by the Fellowship for one year in the first instance.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

St Mark’s Hospital Foundation Seedcorn Fund: £18k + £10k granted in October 2011 and May 2012 respectively.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes