The Effect of Colchicine on Food-related Effort-based Decision Making in Brain and Behaviour in Overweight and Obesity

Overweight and Obesity Clinical Trial

— FLAIR-i  

Official title:

The Effect of Colchicine on Food-related Effort-based Decision Making in Brain and Behaviour in Overweight and Obesity: the FLAIR-i Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05785429
• Other study ID #: 3033002.01
• Secondary ID: 2021-004919-11
• Status: Recruiting
• Phase: N/A
• Start date: August 2, 2022
• Est. completion date: January 2025

Study information

• Verified date: February 2024
• Source: Donders Centre for Cognitive Neuroimaging
• Contact: Judith Scholing, MSc.
• Phone: +31 6 3113 2140
• Email: judith.scholing[@]donders.ru.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objective of the FLAIR-i study is to study the causal role of inflammation in affecting effort-based decision making in brain and behaviour in overweight and obesity, by comparing the effect of the anti-inflammatory agent colchicine vs. placebo.

Description:

Obesity is a major health problem worldwide and is characterized by increases in low-grade, systemic inflammation. Outside the field of obesity, increases in inflammation have been related to loss of motivation and effortful behaviour, which can be objectively measured with effort-based decision making in brain and behaviour. Here, the investigators hypothesise that low-grade inflammation is causing altered striatal brain responses and effortless 'fast food' choices in overweight and obesity. The objective of this study is to study the causal role of inflammation in affecting effort-based decision making in brain and behaviour in overweight and obese participants, by comparing the effect of the anti-inflammatory agent colchicine vs. placebo. In addition, it will be investigated whether this primary objective translates to more ecologically valid measures/settings.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 59 Years

Eligibility

Inclusion Criteria:

• BMI = 27 kg/m2

• Female sex

• Right-handed

• Age: 18-59 years

• Shoulder width of < 68 cm (to fit into the MRI scanner)

• Dutch speaking - Sufficient level to understand task instructions

• Low-grade inflammatory state, as measured by C-reactive protein (CRP) between 3.0 and 10.0 mg/L

Exclusion Criteria:

• Having been vaccinated by any type of vaccine in the 4 weeks preceding the first test session

• Having had an infection characterized by a fever, or diagnosed by a medical physician in the 4 weeks preceding the first test session

• Diagnosed with Diabetes Mellitus type I or II

• Gained or lost >2 points in BMI (kg/m2) over the last 6 months

• Followed an energy restricting diet during the last 2 months

• Having had bariatric surgery in the past 5 years

• Regular use of anti-inflammatory, anti-diabetic, weight-loss, and psychoactive medication

• Regular use of CYP3A4 inhibitors, P-glycoprotein inhibitors, statins, fibrates, ciclosporin, and digoxin, as a contraindication for colchicine

• Have renal impairment as evidenced by serum creatinine >150 µmol/l or eGFR <50mL/min/1.73m2, determined maximum 12 weeks before inclusion

• Have moderate to severe hepatic disease

• (History of) clinically significant psychiatric or neurological disorder

• (History of) clinically significant metabolic, cardiovascular, renal, liver, endocrinological, autoimmune or chronic inflammatory disease

• General medical conditions, such as sensorimotor handicaps, deafness, blindness or colour-blindness, as judged by the investigator

• Current or history of alcohol and/or drugs abuse (i.e. >14 units per week)

• Habitual smoking, i.e. one or more cigarettes per day

• Pregnant, lactating or wishing to become pregnant in the period between the screening and until 3 months after the last study visit

• Participation in another weight loss, lifestyle or anti-inflammatory intervention in the context of research at the time of inclusion or during the study

• Contraindications for MRI

Related Conditions & MeSH terms

• Obesity
• Overweight
• Overweight and Obesity

Intervention

Drug:
• Colchicine 0.5 MG
Participant in the intervention group receive one tablet of 0.5mg colchicine per day for 12 weeks.
• Placebo
Participants in the intervention group receive one tablet of placebo per day for 12 weeks.

Locations

Country	Name	City	State
Netherlands	Donders Centre for Cognitive Neuroimaging	Nijmegen

Sponsors (3)

Lead Sponsor	Collaborator
Donders Centre for Cognitive Neuroimaging	HAN University of Applied Sciences, Radboud University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	C-reactive protein	High sensitive C-reactive protein measured in plasma	Change between baseline and follow-up after 12 weeks
Other	Inflammation profile (blood)	Assay-based profile of systemic inflammation measured in plasma stimulation, Olink Inflammatory profile	Change between baseline and follow-up after 12 weeks
Other	Brain myo-inositol levels	Brain myo-inositol levels reflecting neuroinflammation in ventral striatum and ACC, measured by magnetic resonance spectroscopy	Change between baseline and follow-up after 12 weeks
Other	Abdominal fat distribution	VAT(visceral adipose tissue)/SAT(subcutaneous adipose tissue) ratio based on abdominal MRI scan	Change between baseline and follow-up after 12 weeks
Other	(Resting state) functional connectivity networks	Measured by functional MRI	Change between baseline and follow-up after 12 weeks
Primary	Change in effort valuation in brain and behaviour	Brain activity (BOLD signal during functional MRI) and behavioural weightings upon/of effort sensitivity, as measured by an effort-based decision making task.	Change between baseline and follow-up after 12 weeks
Primary	Change in reward valuation in brain and behaviour	Brain activity (BOLD signal during functional MRI) and behavioural weightings upon/of reward sensitivity, as measured by an effort-based decision making task.	Change between baseline and follow-up after 12 weeks
Secondary	Change effort/reward related food intake ratio	Intake of food items varying in effort and reward/calories, measured by a bogus food taste test.	Change between baseline and follow-up after 12 weeks
Secondary	Change in reward anticipation/reward consummation ratio in daily life	Reward anticipation and reward consummation scores in daily life as measured by the Experience Sampling Method	Change between baseline and follow-up after 12 weeks