Neurobehavioural and Cognitive Changes in Cancer Cachexia (CANCOG) (CANCOG)

Understanding the Impact on CANcer on Neurobehavioral Mechanisms and COGnition in Cachexia (CANCOG)

The goal of this observational study is to to look for changes within the brain, and changes in body-to-brain signals in people with cancer and people who do not have cancer. The main questions it aims to answer are:

1. Are there differences in areas of the brain known to be related to appetite control, food reward and motivation, between participants with cancer related weight loss and healthy volunteers
2. Do responses to questionnaires and computer based tasks suggest participants with cancer related weight loss have reduced appetite and reduced motivation to eat compared to healthy volunteers, and if so, do questionnaires suggest that this is associated with any other symptoms?

Researchers will compare the structure and blood flow in relevant areas of the brain using MRI images between participants with cancer related weight loss and healthy volunteers. Participants will complete questionnaires and computer based tasks to allow researchers to assess areas of the brain which become more active in response to different stimuli. Some computer based tasks will be performed during the MRI scan. This is called functional MRI.

A further objective is to obtain an archive of blood samples which will be stored securely for future analysis if relevant hormones or analytes are identified that may be relevant to metabolism or body composition

Study Overview

• Status: Not yet recruiting
• Conditions: Cancer; Weight Loss; Cachexia; Appetite Loss; Cachexia-Anorexia Syndrome
• Intervention / Treatment: Procedure: MRI/ Functional MRI; Behavioral: Self-reported questionnaires; Behavioral: Computer based tasks

Detailed Description

Cancer cachexia is a complex disorder involving progressive loss of muscle and fat in people with cancer, which cannot be corrected with dietary supplements. It affects 50-80% of the cancer population, and accounts for up to 20% of cancer related deaths.To date there are no effective treatments for cancer cachexia and further research is needed to highlight possible treatments for this condition.

Previous research into conditions such as obesity and anorexia have shown the importance of signals between the body and the brain in controlling appetite. This study will focus on how cancer affects signals within the body which are communicated to the brain. In people with cancer, these signals may be altered, leading to changes in appetite and less pleasure from eating, ultimately resulting in weight loss (cancer cachexia).

The study will be observational and will be carried out in one centre at the Translational Research Facility, Addenbrookes Hospital. Researchers aim to recruit 50 participants (30 with cancer and weight loss, and 20 healthy volunteers).

Potential participants will be identified by clinical teams in oncology clinics, via recruitment posters and multi-disciplinary team meetings on the hospital site. Participants will attend for one study visit lasting 4 hours. During this time, participants will undergo an MRI scan, complete questionnaires and perform computer based tasks. Researchers will look for changes within the brain, and changes in body-to-brain signals in people with cancer and people who do not have cancer. Researchers will assess attitudes to eating and body perceptions using questionnaires and computer based tasks. This will indicate whether cancer is driving changes in behaviour which may cause weight loss (cachexia). The ultimate goal is to develop treatment strategies in future to prevent weight loss and improve outcomes for people with cancer

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Aideen B Daly; Phone Number: 07706585575; Email: ad2075@medschl.cam.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

A maximum of 50 participants will be recruited to this study over a period of 4 years.

This will include approximately 30 participants with cancer, and 20 healthy volunteers. Participants with cancer will be recruited from oncology outpatient clinics or multi-disciplinary team meetings including palliative care MDT meetings at Addenbrooke's Hospital, Cambridge. Healthy volunteers will be recruited by advertising on site, study recruitment notice boards or through a contact of the participant with cancer. Participants in each group will be matched for age and sex

Description

Inclusion Criteria:

General inclusion criteria for all groups:

• Written informed consent
• Aged 18 years or over
• Willing and able to comply with study procedures and visits

Additional inclusion criteria for participants with cancer:

• Histological or cytological diagnosis of a non-haematological cancer or confirmed non intracranial malignancy on imaging.
• Unintended documented weight loss of >5% body weight in 6 months which is felt to be cancer related, OR patient reported weight loss and/or change in appetite

Exclusion Criteria:

General exclusion criteria for all groups:

• Non-fluent English speaker
• Active infection, as determined by the investigator based on clinical symptoms and / or fever and / or requirement for antibiotics
• Women, who are pregnant, plan to become pregnant or are lactating.
• MRI contraindication
• A significant acute, chronic or psychiatric condition which in the judgement of the investigator would place the volunteer at undue risk or interfere with the study
• Metabolically or clinically unstable on day of study visit
• Artificial nutrition
• Taking medications which, as determined by the investigator, may affect appetite or cognition, or otherwise affect completion of study tasks.
• Weight or body circumference above upper threshold for MRI scanner (220kg)
• Unresolved obstructive gastrointestinal (GI) lesion

Additional exclusion criteria for participants with cancer:

• Treatment with chemotherapy, oral steroids, or other immunosuppressive drugs within a week of participation in the study (note- can be included if planned to have a break from these agents)
• Intracranial cancer or metastatic intracranial involvement of cancer

Additional exclusion criteria for healthy volunteers:

• Taking immunosuppressive medications, aspirin or other anti-inflammatories (within the past 7 days)
• Have, or be recovering from, any form of cancer
• Unintentional weight loss of >5% body weight or unexplained loss of appetite

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Participants with cancer and cancer associated weight loss/ loss of appetite; Participants with a non-haematological malignancy, reporting weight loss of >5% body weight in 6 months, or loss of appetite.	Procedure: MRI/ Functional MRI; Participants will undergo an MRI scan lasting approximately 1 hour to examine the structure and function of the brain. During the scan, they will also be asked to perform computer based tasks. This is called functional MRI.; Behavioral: Self-reported questionnaires; Participants will complete questionnaires covering subjective measures relating to food attitudes and intake, and report-based measures of relevant psychopathology including depression and anxiety. These will be derived from standardised scales already used clinically, including the setting of eating disorders and normative studies of the neuroscience of appetite.; Behavioral: Computer based tasks; Participants will complete computer based tasks which are focused specifically on aspects of appetite-related and reward behaviours. Typically, such behaviours are characterised under the following sub-headings: i) Motivation (the amount of effort, cognitive or physical, that a person is prepared to expend in order to gain access to food), ii) Valuation (the relative rating of foods in comparison to each other and to non-food items), and iii) Hedonic response (the subjective pleasure experienced in consumption) to food intake
Healthy volunteers; No malignancy or weight loss in the past 6 months	Procedure: MRI/ Functional MRI; Participants will undergo an MRI scan lasting approximately 1 hour to examine the structure and function of the brain. During the scan, they will also be asked to perform computer based tasks. This is called functional MRI.; Behavioral: Self-reported questionnaires; Participants will complete questionnaires covering subjective measures relating to food attitudes and intake, and report-based measures of relevant psychopathology including depression and anxiety. These will be derived from standardised scales already used clinically, including the setting of eating disorders and normative studies of the neuroscience of appetite.; Behavioral: Computer based tasks; Participants will complete computer based tasks which are focused specifically on aspects of appetite-related and reward behaviours. Typically, such behaviours are characterised under the following sub-headings: i) Motivation (the amount of effort, cognitive or physical, that a person is prepared to expend in order to gain access to food), ii) Valuation (the relative rating of foods in comparison to each other and to non-food items), and iii) Hedonic response (the subjective pleasure experienced in consumption) to food intake

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterise structural and functional neuroanatomy as well as neurometabolism through MRI brain imaging in participants with cancer related weight loss and healthy volunteers.	Eligible participants will undergo an MRI scan during a 1-hour scanning session at Wolfson Brain Imaging Centre.	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine if there is a difference in food motivation and reward -based behaviour using functional MRI.	Participants will be asked to perform one computer based task during their MRI scan, which is called functional MRI. Imaging analysis of the results of this task will indicate differences in MRI responses in areas of the brain related to food reward and food motivation, between people with cancer and weight loss and healthy volunteers.	1 hour
Participants will be asked to perform two computer based tasks after the MRI scan, which have been validated to assess food reward and motivation.	Participants will be asked to perform two computer based tasks using a laptop. The generated results of these tasks will indicate participants' level of food reward and food motivation and will allow for comparison between people with cancer and weight loss, and healthy volunteers.	2 hours
To secure an archive of blood samples for potential future analysis as other targets may become available with research progression locally or within the wider CANCAN consortium	A 10-20ml blood sample will be collected from all participants	5 minutes
To compare responses to questionnaire-based measures of food attitudes, food intake and relevant psychopathology across patients with cancer related weight loss and healthy volunteers.	The following questionnaires cover food attitudes and intake, and measures of psychopathology including depression and anxiety. These will be derived from standardised scales, used the setting of eating disorders and neuroscience of appetite studies. Questionnaire scores will be compared between people with cancer and weight loss and healthy volunteers. Godin Leisure Time Exercise Questionnaire Functional Assessment of Chronic Illness Therapy- Fatigue Functional Assessment of Anorexia/Cachexia Therapy Activities of daily living questionnaire Instrumental activities of daily living scale Scored Patient Generated Subjective Global Assessment Edmonton Symptom Assessment Brief Pain Inventory Patient Health Questionnaire- 9 General Anxiety disorder Hospital Anxiety and Depression Scale Body Perception Questionnaire Snaith Hamilton Pleasure Scale The three factor eating questionnaire DSM-5 Self rated Level 1 Cross-cutting symptom measure	1 hour

Collaborators and Investigators

• Sponsor: University of Cambridge
• Investigators: Principal Investigator: Anthony P Coll, University of Cambridge

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: October 24, 2023
• First Submitted That Met QC Criteria: October 30, 2023
• First Posted (Actual): November 2, 2023

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Signs and Symptoms, Digestive; Nutrition Disorders; Body Weight; Body Weight Changes; Thinness; Anorexia; Weight Loss; Wasting Syndrome; Cachexia
• Other Study ID Numbers: A096708

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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