Reduced Appetite in Crohn's Disease: The Role of the Brain in the Control of Food Intake

• ClinicalTrials.gov Identifier: NCT02772458
• Recruitment Status: Completed
• First Posted: May 13, 2016
• Last Update Posted: April 17, 2019
• Sponsor: University of Nottingham
• Information provided by (Responsible Party): University of Nottingham

Study Description

Brief Summary:

Crohn's disease (CD) is becoming more common, specifically in the western world. One of the main features of this disease is weight loss and malnutrition. Although clinically common, these problems are not well understood. Loss of appetite and symptoms such as tummy aches and bloating are common causes for weight loss in this group of patients. This problem has a strong negative effect on the patients' quality of life and significantly increases the cost of treating CD. Enteroendocrine cells are nutrient sensors in the bowel that relay to the brain to control food intake. Recent evidence has showed that these cells increase in number in active CD and secrete more hormones that negatively affect appetite. The increased levels of these hormones should have an overall negative effect on the brain and thus decrease food intake, bloating, symptoms of sickness. All these symptoms lead to malnutrition. These are hypotheses that require further proof. Current technological advances in magnetic resonance imaging (MRI) has enabled the mapping of changes in activity in important areas in the brain that control food intake. The involvement of the brain in control of food intake is still not fully understood. This work will be the first step in the right direction to start targeting the problems of appetite, weight loss and a poor quality of life.

Condition or disease	Intervention/treatment	Phase
Crohn's Disease	Other: Dodecanoate acid and saline	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Reduced Appetite in Crohn's Disease: Investigating the Role of the Gut Brain Pathways
• Study Start Date: June 2015
• Actual Primary Completion Date: September 2018
• Actual Study Completion Date: September 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Crohn's Disease; Active Crohn's Disease	Other: Dodecanoate acid and saline; Test drink
Experimental: Healthy; Healthy volunteers	Other: Dodecanoate acid and saline; Test drink

Outcome Measures

Primary Outcome Measures :

1. Changes in Blood Oxygenation Level Dependent (BOLD) response in the brain following a fatty acid test meal in Crohn's patients and healthy controls [ Time Frame: 3 years ]

Secondary Outcome Measures :

1. Changes in arterial spin labeling measures of cerebral blood flow and changes in gut peptide levels following the fatty acid test meal. [ Time Frame: 3 years ]

   The increase or decrease in BOLD signal of the brain following the fatty acid stimuli will be correlated to the gut peptide levels which are listed as follows:

   1. CCK (pmol/ml)
   2. GLP-1 (pM)
   3. PYY (pg/ml)
   4. Ghrelin (ng/ml)

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 75 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Age 16-75 years
2. Ulceration seen at ileocolonoscopy, aiming for a simple endoscopic score for Crohn's disease (SES-CD) of 4-19, in the absence of stricturing disease or,
3. Intestinal inflammation or deep ulceration seen on CT or MR enterography, with the disease activity quantified via the MaRIA score or,
4. Faecal calprotectin of >250µg/g
5. C-Reactive protein >5mg/dl
6. Harvey-Bradshaw index score of 5-16
7. Body mass index (BMI) 18-35
8. As for HV participants, inclusion criteria 1 and 7 will apply.

Exclusion Criteria:

1. Malignant disease
2. BMI <18 and >35
3. Significant cardiovascular or respiratory disease
4. Diabetes mellitus
5. Current Infection
6. Neurological or cognitive impairment; significant physical disability
7. Significant hepatic disease or renal failure
8. Abnormal blood results other than those explained by CD including bleeding diatheses (apart from in the case of HV where all unexplained blood results are an exclusion criteria)
9. Subjects currently participating in (or in the last three months) any other research project
10. pregnancy or breastfeeding or
11. if MRI is contraindicated (e.g. pacemaker).
12. Severe Crohn's disease where a delay in a change in medical treatment for 23 weeks would not be clinically advisable.
13. As for healthy volunteer participants all exclusion criteria apart from no.12.

Contacts and Locations

Locations

United Kingdom

University of Nottingham

Nottingham, United Kingdom, NG7 2RD

University of Nottingham

Nottingham, United Kingdom

Sponsors and Collaborators

University of Nottingham

More Information

• Responsible Party: University of Nottingham
• ClinicalTrials.gov Identifier: NCT02772458
• Other Study ID Numbers: 14038
• First Posted: May 13, 2016
• Last Update Posted: April 17, 2019
• Last Verified: October 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by University of Nottingham:

Crohn's Disease; gut brain axis; reduced appetite

Additional relevant MeSH terms:

Crohn Disease; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases