Treatment-Resistant Major Depressive Disorder
Conditions
Brief summary
Clinical trial aimed at evaluating whether a single infusion of tocilizumab, a medication that blocks the action of an inflammatory molecule called interleukin-6 (IL-6), can reduce symptoms of treatment-resistant major depression compared to placebo in non-hospitalized patients.
Interventions
BIOLOGICALTocilizumab
Single infusion tocilizumab, 8 mg/kg, diluted in 100 mL of normal saline
DRUGNormal Saline (0.9% NaCl)
Placebo, same volume as intervention
Sponsors
Hospital de Clinicas de Porto Alegre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Age ≥ 18 years Provide informed consent Understand written and spoken Portuguese Able and willing to consent to blood sampling Willing to abstain from strenuous exercise for 72 hours prior to assessment Meet DSM-5/MINI criteria for a diagnosis of depression resistant to at least two adequate courses of treatment at the time of eligibility assessment Baseline HDRS score of 19 or higher at Serum/plasma CRP level ≥3 mg/L
Exclusion criteria
Diagnosis of bipolar disorder or personality disorder History of substance use disorder in the past six months. Presence of active/recent infection (including TB, Hepatitis B, Hepatitis C, or HIV) or autoimmune disease Pregnancy or breastfeeding History of significant cardiovascular disease, recent cancer, or hematological disorders BMI \>40 kg/m² or weight \>100 kg Hypersensitivity to tocilizumab or any of its excipients. CRP ≥20 mg/L Active liver disease or transaminase elevation \>1.5× the upper limit of normal Inclusion criteria to the 10 healthy controls recruited for comparison of inflammatory biomarkers: Age ≥ 18 No current or lifetime psychiatric diagnosis, as measured by the SRQ-20 Provide informed consent Understand written and spoken Portuguese Able and willing to consent to blood sampling
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in depressive symptoms (HDRS) | Baseline and follow-ups (day 7, day 14, day 28 and month 6) | ≥50% reduction in score |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Psychiatric hospitalization rate in 6 months | 6 months follow-up | — |
| Suicidal ideation (MINI) | Elegibility and follow-ups (day 7, day 14, day 28 and month 6) | — |
| Quality of life (WHOQOL-BREF) | Baseline, follow-ups (day 7, day 14, day 28 and month 6) | — |
| General psychiatric symptoms improvement (BPRS) | Baseline and follow-ups (day 7, day 14, day 28 and month 6) | — |
| Clinical global improvement (CGI) | Baseline and follow-ups (day 7, day 14, day 28 and month 6) | — |
| CRP levels | Baseline and follow-ups (day 7, day 14, day 28 and month 6) | Serum C-Reactive Protein levels |
| BDNF levels | Baseline and third follow-up post-intervention (28th day) | Serum Brain-Derived Neurotrophic Factor level |
| ECT indication after invervention | Follow-ups (day 7, day 14, day 28 and month 6) | — |
| Cognitive performance (Montreal Cognitive Test) | Baseline and follow-ups (day 7, day 14, day 28 and month 6) | — |
| IL-6 levels | Baseline (for healthy controls) and baseline and follow-ups for intervention arm(day 7, day 14, day 28 and month 6) | Serum IL-6 |
| Quality of life (EUROHISQOL8) | Baseline and follow-ups (day 7, day 14, day 28 and month 6) | — |
Countries
Brazil
Contacts
CONTACTNeusa Sica da Rocha, PhD
STUDY_DIRECTORNeusa Sica da Rocha, PhD
Federal University of Rio Grande do Sul (UFRGS)
Outcome results
None listed