Introduction
The need for partnerships and formation of the LBDA IAC
Diagnostic criteria and standards of care for LBD
Current state of clinical trials in LBD
ClinicalTrials.gov identifier | Population | Drug/intervention | Mechanism | Trial design | Primary outcome | Results for primary outcome |
---|---|---|---|---|---|---|
NCT03305809 | DLB or PDD | Mevidalen | D1 positive allosteric modulator (D1PAM) | Phase 2, DB-PC | CDR computerized cognition battery continuity of attention composite score | Ongoing |
NCT03413384 | PDD | Ceftriaxone | Glutamatergic activity, excitotoxicity reduction | Phase 2, DB-PC | ADAS-Cog | Ongoing |
NCT02914366 | PDD | Ambroxol | Raise beta-Gcase, lower α-synuclein | Phase 2, DB-PC | ADAS-Cog, ADCS-CGIC | Ongoing |
NCT03774459 | PDD | Anavex2-73 | Cellular homeostasis restoration via sigma-1 and muscarinic receptors | Phase 2, DB-PC | CDR computerized cognition battery continuity of attention composite score, safety | Ongoing |
NCT03713957 | PDD or PD-MCI | GRF6021 | Plasma-derived product | Phase 2, DB-PC | Safety | Ongoing |
NCT03467152 | DLB | E2027 | Selective phosphodiesterase inhibitor type 9 | Phase 2, DB-PC | MoCA, CIBIC+ | Ongoing |
NCT04002674 | DLB | Nilotinib | Tyrosine kinase inhibitor | Phase 2, DB-PC | Safety, tolerability | Ongoing |
NCT02669433 | DLB | Intepiridine | 5HT-6 antagonist | Phase 2, DB-PC | UPDRS Part 3 | Negative |
NCT01023672 | DLB | Armodafinil | Unknown | Open-label, pilot | ESS, MWT | Positive |
NCT01340001 | DLB | DBS of nucleus basalis of Meynert | Neuromodulation | Open-label, pilot | Free recall on FCSRT | Completed no results yet |
NCT02258152 | PDD | SYN120 | 5HT-6/5HT-2A antagonist | Phase 2, DB-PC | CDR computerized cognition battery continuity of attention | Negative |
NCT01701544 | PDD | DBS of nucleus basalis of Meynert | Neuromodulation | Open-label, pilot | Abbreviated cognitive battery, safety | Safe but no cognitive improvement |
NCT02640729 | DLB or PDD with VH | Nelotanserin | 5HT-2A antagonist | Phase 2, DB-PC, cross-over | Safety, UPDRS Part 3 | Safe/well tolerated but no significant changes on endpoints |
NCT03325556 | DLB or PDD with psychosis | Pimavanserin | 5HT-2A inverse agonist/antagonist | Phase 3, time to event | Time to relapse | Positive |
NCT02708186 | DLB or PDD with RBD | Nelotanserin | 5HT-2A antagonist | Phase 2, DB-PC | RBD frequency | Negative |
Optimizing clinical trial design in LBD (Table 2, Fig. 1)
Study population
Category | Barriers and challenges |
---|---|
Trial focus | - Need for both disease-modifying and symptomatic trials - Lack of studies focusing on the breadth of LBD symptoms, including non-cognitive outcomes |
Study population | - Delays in LBD diagnosis - Heterogeneity of clinical symptomatology - Co-morbidities (e.g., cerebrovascular disease) - Concomitant medication use (e.g., cholinesterase inhibitors, antipsychotics, parkinsonian medications) |
Recruitment and retention | - Cognitively impaired population - Lack of under-represented minorities in studies - Complex and long assessment batteries - Study procedures (e.g., lumbar puncture, imaging) - Caregivers with high degrees of burden and stress - Long travel distances to study centers - Retention of older adults with combined cognitive, behavioral, and motor symptoms |
Selection of outcome measures | - Lack of LBD-specific outcome measures - Existing outcome measures designed more for use in AD trials - Optimal outcome for different symptoms is uncertain - Existing outcome measures often lack validated measurement properties for LBD (e.g., inter-rater reliability, sensitivity to change) |
Study execution | - Medication effects on attention and alertness - Cognitive fluctuations, which may affect test performance - “On” and “off” timing in individuals with Parkinson’s disease |
Biomarkers | - Lack of biomarkers of progression - Lack of established α-synuclein biomarkers (imaging, biofluid) - Biomarkers in DLB criteria focus on diagnosis rather than clinical trial use - Lack of biomarker standardization - Lack of availability or access to some biomarker studies (e.g., dopaminergic imaging, polysomnography, cardiac MIBG) |