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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Overweight and Obesity

Intervention / Treatment
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* Drug: Colchicine 0.5 MG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Overweight, Obesity, Inflammation, fMRI, Motivation