Depressive episode Mental and Behavioural Disorders Depressive episode, unspecified
Conditions
Interventions
A proof-of-concept, randomized, double blind, placebo-controlled experiment based on approximately 50 depressed participants (intervention cohort) who have evidence of low-grade inflammation (i.e., se
max 800 mg in total). Behavioural data and blood samples will be collected at baseline and after infusion around day 7, 14 and 28. Cognitive tasks will be performed at baseline and after infusion arou
Sponsors
Cambridgeshire and Peterborough NHS Foundation Trust
University of Cambridge
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria for all participants: 1. Able and willing to give informed consent, including consent to share information with the participant’s General Practitioner (GP) and to access GP records 2. Able to understand written and spoken English 3. Able to consent to blood sampling 4. Willing to abstain from strenuous exercise for 72 hours before the assessment visits 5. Age: 20-65 years (inclusive) at the time of eligibility assessment 6. Diagnosis of depression: meet ICD-10 criteria for diagnosis of depression at the time of eligibility assessment 7. Somatic symptom score: =7 at the time of eligibility assessment based on Beck depression inventory II (BDI-II) items 4=lack of pleasure, 15=loss of energy, 16=changes in sleeping pattern, 18=changes in appetite, 19=concentration difficulty, 20=tiredness or fatigue, and 21=loss of interest in sex 8. History of non/slow response to antidepressant: at the time of eligibility assessment receiving treatment with an antidepressant at adequate dose (according to BNF) for at least four weeks Additional inclusion criteria for intervention cohort: 1. Inflamed: serum/plasma hsCRP level =3mg/L
Exclusion criteria
Exclusion criteria: Exclusion criteria for all participants: 1. Current or lifetime diagnosis of bipolar disorder, psychotic disorder, personality disorder or eating disorder 2. Current suicidal thoughts (BDI II item 9=suicidal thoughts or wishes score 2 or more) or history of suicide attempt, deliberate self-harm, overdose within six months prior to eligibility assessment 3. History of alcohol or substance use disorder (abuse/dependence) within six months prior to eligibility assessment (nicotine and caffeine dependence are not exclusionary) 4. Pregnant or breastfeeding 5. History of serious allergic reaction after any infusion 6. Current use of medication likely to compromise interpretation of immunological data (including, but not limited to, antibiotics, non-steroidal anti-inflammatory drugs, oral/injectable corticosteroids – or any other substances to be determined by the Chief Investigator) 7. Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of eligibility assessment 8. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other opportunistic infections 9. Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active infectious disease, including current or prior malignancy 10. Rheumatic autoimmune disease, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to rheumatoid arthritis 11. Uncontrolled hypertension defined as systolic blood pressure > 170 or diastolic blood pressure > 110 12. No history of chickenpox infection or no history of varicella zoster vaccination Additional exclusion criteria for intervention cohort: 1. Current or past infection with TB, Hepatitis B, Hepatitis C, VZV or HIV confirmed by blood/other test. Chest X-ray will be also done to exclude TB 2. Pregnancy test (for female participants) 3. History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in total somatic symptoms score from baseline assessment to around day 14 post-infusion. Somatic symptom score will be constructed by summing scores for seven relevant Beck Depression Inventory II (BDI-II) items (4=lack of pleasure, 15=loss of energy, 16=changes in sleeping pattern, 18=changes in appetite, 19=concentration difficulty, 20=tiredness or fatigue, and 21=loss of interest in sex). Somatic symptoms will be measured using BDI-II at baseline, day 7, 14 and 28 post-infusion. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary outcome measure: Change in total depression severity score from baseline assessment to around day 14 post-infusion assessed by BDI-II. Depression severity will be measured using BDI-II at baseline, day 7, 14 and 28 post-infusion. Tertiary/exploratory outcome measures: Behavioural measures: 1. Fatigue, assessed by Multi-dimensional Fatigue Inventory (MFI) at baseline, day 7, 14 and 28 post-infusion 2. Anhedonia, assessed by Snaith-Hamilton Pleasure Scale Questionnaire at baseline, day 7, 14 and 28 post-infusion Cognitive measures: 1. Psychomotor speed, assessed by CANTAB Reaction Time (RTI) test or a similar test (computerised) and Digit Symbol Substitution Test (pen and paper) or a similar test at baseline and day 14 post-infusion 2. Attention, assessed by CANTAB Rapid Visual Information Processing (RVP) test or a similar test (computerised) at baseline and day 14 post-infusion 3. Memory, assessed by CANTAB Paired Associates Learning (PAL) test or a similar test (computerised) at baseline and day 14 post-infusion 4. Emotional processing, assessed by Emotional categorization and recall task or a similar task (computerised) at baseline and day 14 post-infusion Blood biomarkers will be measured using appropriate tests at baseline and post-infusion follow-up. These include but are not limited to inflammatory markers, cortisol, cardio-metabolic markers, and phenotyping of peripheral blood mononuclear cell populations (PBMC). Genetic analysis of blood samples will be carried out using appropriate methods at baseline and post-infusion follow-up. | — |
Countries
England, United Kingdom
Outcome results
None listed