Comorbid Obesity and Depression With an Anti-inflammatory Medication

NCT06537921 | Recruiting

• 1 other identifier: IRAS ID: 333466
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Obesity; Major Depressive Disorder; Inflammation

Keywords

Psychiatry; Immune System; Immunity

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (1)

Comorbid depression and obesity

EXPERIMENTAL

Participants with comorbid major depressive disorder (MDD) and obesity (BMI≥30 kg/m2) and c-reactive protein (CRP) levels ≥3mg/L at screening.

Drug: Minocycline 200mg

Interventions

Minocycline 200mg DRUG

Dosage: 2x100mg/daily for 8 weeks

Comorbid depression and obesity

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sufficient communication skills to understand the intervention and complete the assessments.
• Able to give informed consent.
• Treatment resistant depressed (i.e., non-responders to current antidepressant treatment, for at least 6-weeks AND at least one other previous antidepressant).
• Tolerant to the current antidepressant.
• Able to undergo 2 MRI scans.
• Accepting augmentation with minocycline.
• CRP \>3mg/L at screening.
• No plans to change current therapy for the duration of participation.

You may not qualify if:

• Active suicidal ideation.
• Current primary diagnosis of psychotic disorder, bipolar disorder, obsessive-compulsive disorder, or post-traumatic stress disorder.
• Have an acute infection or an autoimmune disorder, because of both the rare but described association between minocycline and systemic lupus erythematosus, and the potential confounder effects of these conditions on immune biomarkers.
• Alcohol misuse disorder or drug addiction.
• Neurological disorders (Parkinson's, Alzheimer's).
• Current serious cardiovascular problems.
• Have acne or psoriasis.
• Currently taking any antibiotic, immunosuppressive medication, or warfarin.
• Taken any tetracycline within the last month.
• Currently taking Lithium or retinoids (Acitretin, Alitretinoin, Isotretinoin).
• Refuse that we contact their GP to inform them about their participation.
• \[OPTIONAL - if not met, cannot undergo the MRI\] Has any metal implants in their body such as pacemakers, dental fillings, IUD device (if applicable), or had any accidents where metal fragments might have entered the body or eye.
• Pregnant or breastfeeding
• Have a positive pregnancy test before starting the study/are unwilling to take a pregnancy test and are unwilling to agree to use an acceptable form of contraceptive throughout the study period (e.g., condoms, intrauterine device (IUD)/intrauterine system (IUS), injection, patch, ring). Female participants who use combined oral contraceptives as their main form of birth control will need to use an additional barrier method for the duration of treatment and for 7 days following completion of treatment.
• Are currently participating in another Clinical Trial of Investigational Medicinal Product (CTIMP).

Sponsors & Collaborators

• King's College London: lead
• South London and Maudsley NHS Foundation Trust: collaborator

Study Sites (1)

King's College London

London, SE5 9RT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Obesity; Depressive Disorder, Major; Inflammation

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Depressive Disorder; Mood Disorders; Mental Disorders; Pathologic Processes

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Central Study Contacts

Valeria Mondelli

CONTACT

+442078480353; valeria.mondelli@kcl.ac.uk

Melisa Kose

CONTACT

+442078485440; melisa.kose@kcl.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Feasibility

Study Record Dates

• First Submitted: March 28, 2024
• First Posted: August 5, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: November 14, 2025

Record last verified: 2025-05

Locations

GB (1)