Comorbid Obesity and Depression With an Anti-inflammatory Medication
NCT Number: NCT06537921
Acronym: CODA
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Obesity|Major Depressive Disorder|Inflammation
Interventions: DRUG: Minocycline 200mg
Sponsor: King's College London
Collaborators: South London and Maudsley NHS Foundation Trust
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 35
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: OTHER
Start Date: 2024-09-01
Completion Date: 2027-09-01

Summary:
Research suggests that only a subset of individuals with major depressive disorder (MDD) may benefit from anti-inflammatory treatments: those who have C-reactive protein (CRP) ≥3 mg/L, a commonly used threshold for "low-grade" inflammation. The emerging link between metabolic and immune abnormalities in MDD suggests that individuals with comorbid obesity and MDD are a subset of people who could particularly benefit from anti-inflammatory treatment. The coexistence of obesity and MDD has been shown to amplify the risk of clinically elevated CRP levels (≥3mg/L). Therefore, people with comorbid obesity, MDD, and CRP ≥3mg/L could be an ideal target population in future randomised clinical trials (RCTs). However, investigation into the feasibility and acceptability of inflammation-targeting treatment in this population is needed first.

Meta-analyses identify minocycline (a tetracycline antibiotic that can cross the blood-brain barrier) as one of the most effective inflammation-targeting medications with antidepressant effects. Minocycline can safely be used long-term at dosages of up to 200mg per day and has low tendency to lead to antibiotic resistance. A pilot RCT of minocycline found a large effect size (Cohen's d=0.98, p\<0.001) for the reduction of MDD symptoms compared with placebo. This effect size was even larger (Cohen's d=1.5, p\<0.005) in another RCT using minocycline when considering only participants with CRP ≥3mg/L.

One mechanism through which minocycline could ameliorate MDD symptoms appears to involve the activation of indoleamine 2,3-dioxygenase (IDO), which leads to an increase in the expression and function of the serotonin transporter. Studies exploring this anti-inflammatory effect in MDD demonstrate that minocycline indeed can inhibit IDO.

Another pathway through which minocycline could ameliorate MDD symptoms is through the reduction of inflammation at the central level. Minocycline has been shown to reduce microglia activation in preclinical models. Previous literature reports an impact of neuroinflammation on white matter microstructure and brain structure in patients with MDD and in individuals with obesity. Minocycline's effect on white matter structure and myelination has not yet been investigated in humans in vivo. Investigating whether neuroimaging biomarker candidates associated with neuroinflammation could be detected in this study design is needed.

Primary Outcome Measures: Enrolment rate, Percentage of participants who consent at the Screening Visit who begin their 8-week course of minocycline., Throughout recruitment and screening period|Intervention adherence, Percentage of participants who complete, in full, the 8-week course of minocycline, alongside their usual antidepressant, and the accompanying medication diary. (N=35), 8 weeks|Outcome and Biomarker Measurements, Percentage of participants who complete all outcome measurements (i.e., interviews and questionnaires), blood and saliva sample collections (N=35), and all MRI procedures (N=15) at all time points., 8 weeks + 12 week follow-up|Effect size calculations, Effect size calculation and power calculation for a range of blood-based and neuroimaging biomarkers changes to inform the design of a future randomised clinical trial (RCT)., 12 weeks