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

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

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.

Study Overview

• Status: Completed
• Conditions: Overweight and Obesity
• Intervention / Treatment: Drug: Colchicine 0.5 MG; Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 9525EN
    • Donders Centre for Cognitive Neuroimaging

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colchicine; One tablet of colchicine 0.5 mg per day	Drug: Colchicine 0.5 MG; Participant in the intervention group receive one tablet of 0.5mg colchicine per day for 12 weeks.
Placebo Comparator: Placebo; One tablet of microcrystalline cellulose per day	Drug: Placebo; Participants in the intervention group receive one tablet of placebo per day for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-reactive protein	High sensitive C-reactive protein measured in plasma	Change between baseline and follow-up after 12 weeks
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
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
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
(Resting state) functional connectivity networks	Measured by functional MRI	Change between baseline and follow-up after 12 weeks

Collaborators and Investigators

• Sponsor: Donders Centre for Cognitive Neuroimaging
• Collaborators: Radboud University Medical Center; HAN University of Applied Sciences
• Investigators: Principal Investigator: Esther Aarts, Prof.dr., Donders Centre for Cognitive Neuroimaging

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2022
• Primary Completion (Actual): January 20, 2025
• Study Completion (Actual): January 20, 2025

Study Registration Dates

• First Submitted: September 27, 2022
• First Submitted That Met QC Criteria: March 14, 2023
• First Posted (Actual): March 27, 2023

Study Record Updates

• Last Update Posted (Estimated): September 2, 2025
• Last Update Submitted That Met QC Criteria: August 25, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Inflammation; Obesity; Overweight; Motivation; fMRI
• Additional Relevant MeSH Terms: Pathologic Processes; Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Inflammation; Heterocyclic Compounds; Substandard Drugs; Pharmaceutical Preparations; Alkaloids; Colchicine; Counterfeit Drugs
• Other Study ID Numbers: 3033002.01; 2021-004919-11 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No