Table 1.
Summary of ongoing clinical trials investigating the efficacy of anti-tumor necrosis factor alpha biologic infliximab on a measure of anhedonia.
| Study location [ClinicalTrials.gov identifier] | Recruitment status (estimated study completion date) | Study design | Intervention | Participants | Primary outcome measure | Secondary outcome measures |
|---|---|---|---|---|---|---|
| Toronto Western Hospital, University Health Network, Toronto, Canada; VA Palo Alto Health Care System, Stanford University, Palo Alto, USA [NCT02363738] | Completed (April 2018) | Phase II, 12-week randomized, placebo-controlled clinical trial with masking of participant, investigator, outcomes assessor, and care provider | Three infusions of adjunctive infliximab (5 mg/kg) versus saline at weeks 0, 2, 6 (parallel assignment) | Adults (n = 60) ages 18–65 with current MDE as part of BD-I/II exhibiting baseline inflammatory activation (obesity and hypertension/dyslipidemia, diabetes mellitus, inflammatory bowel disorder, rheumatoid arthritis, psoriasis, daily cigarette smoking, or baseline CRP ⩾ 5 mg/l) | MADRS total score (change from baseline to up to week 12) | Anhedonia (SHAPS), plasma cytokine levels, cognitive function (DSST, RAVLT, PDQ-D-20), structural MRI and MRS, quality of life (SF-36), functional disability (SDS, EWPS), suicide risk (CSSRS) |
| Emory University, Atlanta, USA [NCT03006393] | Recruiting (November 2021) | Phase I, 2-week, randomized, placebo-controlled clinical trial with masking of participant and investigator | Single infusion of infliximab (5 mg/kg) versus saline (parallel assignment) | Adults (n = 80) ages 25–60 with current MDE as part of MDD or BD with baseline CRP > 3 mg/l | fMRI-adapted behEEfRT with two task difficulty level choices (change from baseline to week 2) | Anhedonia (SHAPS, MAP), fatigue (MFI, FSS), overall depressive symptom severity (IDS-SR), emotional states (PANAS-X), suicide risk (CSSRS), cognition (Go/No-Go, RTT, DSST), motor control (FTT), plasma biomarkers (CRP, TNF-alpha, sTNFR1, sTNFR2, IL-1, IL-1RA, IL-6, sIL-6R) |
| Emory University, Atlanta, USA [NCT03004443] | Recruiting (March 2021) | Phase IV, 2-week, randomized, placebo-controlled clinical trial with masking of participant, investigator, and outcomes assessor | Single infusion of infliximab (5 mg/kg) versus saline (parallel assignment) | Adults (n = 60) ages 25–60 with current MDE as part of MDD or BD with baseline CRP > 3 mg/l | Basal ganglia glutamate, assessed by MRS (change from baseline to day 3 to 14) | Anhedonia (SHAPS, MAP), motivation (EEfRT), motor control (FTT), cognition (RTT, DSST, TMT-A), psychomotor retardation (RSS), fatigue (MFI), overall depressive symptom severity (IDS-SR), plasma and CSF inflammatory markers (CRP, TNF, TNFR2, IL-1RA, IL-6, sIL-6R, IL-10, MCP-1, mRNA) |
BD: bipolar disorder; behEEfRT: behavioral EEfRT; CRP: C-reactive protein; CSF: cerebrospinal fluid; CSSRS: Columbia Suicide Severity Rating Scale; DSST: Digit Symbol Substitution Test; EEfRT: Effort-Expenditure for Rewards Task; EWPS: Endicott Workplace Productivity Scale; FSS: Fatigue Severity Scale; IDS-SR: Inventory of Depressive Symptoms Self-Report; IL: interleukin; IL-1RA: IL-1 receptor agonist; MADRS: Montgomery-Asberg Depression Rating Scale; MAP: Mood and Pleasure Scale; MCP: monocyte chemoattractant protein; MDD: major depressive disorder; MDE: major depressive episode; MFI: Multidimensional Fatigue Inventory; MRI: magnetic resonance imaging; mRNA, messenger ribonucleic acid; MRS: magnetic resonance spectroscopy; PANAS-X: Positive Affect/Negative Affect Scale: now; PDQ-D-20: Perceived Deficits Questionnaire: Depression, 20-item; RAVLT: Rey Auditory Verbal Learning Test; SDS: Sheehan Disability Scale; SF-36: 36-item Short Form health survey; RTT: Reaction Time Task; SHAPS: Snaith-Hamilton Pleasure Scale; sIL-6R: soluble IL-6 receptor; TMT: Trail-Making Test; TNF: tumor necrosis factor; TNFR: TNF receptor; VA, Veterans Affairs.