Table 2 Barriers and challenges to developing clinical trials in Lewy body dementia
From: Challenges and opportunities for improving the landscape for Lewy body dementia clinical trials
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) |