Table 2.

Current active and upcoming LBD drug intervention trials (symptomatic and disease modification) listed on ClinicalTrials.gov (accessed on October 23, 2021)

Drug	Mechanism of action	Condition(s)	Primary outcome(s)	Secondary outcome(s)	ClinicalTrials.gov identifier	Phase	Recruitment status
Ambroxol hydrochloride	Glucocerebrosidase (GCase) chaperone	LBD (MoCA 18–24)	• MMSE • EKG abnormalities • Abnormal changes in hemodynamic values (sitting, standing) • Ambroxol levels in CSF and blood • GCase levels in CSF and white blood cells • Adverse events •Treatment/study discontinuation	• Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) • CGIC • MoCA • Trail making Test A and B • NPI • GDS • UPDRS-III • Timed up and go • Change in brain MRI hippocampal atrophy • Change in LBD-related plasma and CSF biomarkers (alpha-synuclein, tau, phospho-tau, beta amyloid-42)	NCT04405596	1/2	Not yet recruiting
Ambroxol hydrochloride	Glucocerebrosidase (GCase) chaperone	DLB (MMSE ≥ 15)	• Change in adverse events • Number of treatment discontinuation • Rate of EKG abnormalities • Change in clinical labs • MMSE-NR3 (Norwegian revised version) • ADCS-CGIC (Clinician’s Global Impression of Change) • CDR-SB (Clinical Dementia Rating-Sum of Boxes) • NPI • GDS	• Mayo Sleep Questionnaire (MSQ) • Mayo Fluctuation Scale (MFS) • UPDRS-III • Number of falls/related injuries	NCT04588285	2	Recruiting
Terazosin	Alpha-1–selective adrenergic blocker	DLB (MoCA > 18)	• Brain ATP concentration as measured by 31P-magnetic resonance spectroscopy	• Change in blood pressures • UPDRS III • Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) • MoCA • CIBIC-plus • NPI • FDG-PET • Serum ATP and terazosin levels	NCT04760860	1/2	Not yet recruiting
K0706	Tyrosine kinase inhibitor	DLB (MoCA ≥ 14)	• Treatment-emergent adverse effects	• K0706 concentration in plasma and CSF • Changes in DLB related biomarkers in plasma and CSF (HVA, DOPAC, Abeta40/42, total tau, ptau231/181 and total and oligomeric alpha-synuclein)	NCT03996460	2	Recruiting
Nilotinib	Tyrosine kinase inhibitor	DLB (MoCA ≥ 18)	• Occurrence of adverse events	• Nilotinib levels in CSF and plasma • Changes in DLB related CSF and plasma biomarkers (e.g., HVA) • Quantify amyloid burden via Florbetaben PET scan	NCT04002674	2	Recruiting
E2027	Selective inhibitor of phosphodiesterase-9	•LBD •PD (MMSE 14–26)	• Change in CSF cGMP at 9 weeks of treatment	Percentage of participants with: • Adverse events • Orthostatic hypotension and tachycardia • Markedly abnormal lab values • EKG findings • Suicidal ideation/behavior • UPDRS-III	NCT04764669	2	Recruiting
NYX-458	NMDA receptor modulator	•MCI •PD •LBD •Mild dementia (MoCA 15–25)	• Change in baseline physical exam • Rate of adverse events and early termination • Change in vital signs, labs, EKG • Change in neuropsychiatric symptoms based on NPI-12 • Change in suicidal ideation by Sheehan Suicidality Tracking Scale • Change in MDS-UPDRS Part 4	• Change in working memory (1-Back and 2-Back Tests) • Change in problem solving/reason (Groton Maze Learning) • Change in visual attention (Identification Test) • Change in verbal learning (International Shopping List Test (ISLT)) • Change in visual associate memory (Continuous Paired Associate Learning Test)	NCT04148391	2	Recruiting
CST-103 (clenbuterol) co-administered with CST-107 (nadolol)	Clenbuterol: β2 adrenergic agonist Nadolol: non-selective beta blocker (Being given in combination to reduce the side effect of clenbuterol, e.g., tachycardia)	•MCI •LBD •PD RBD •PDD (MoCA 18–28)	• Negative Emotional Bias in the Facial Expression Recognition Task (FERT) • Cognitive fluctuations (EEG, activity tracking, pupil measurements, Dementia Cognitive Fluctuation Scale (DCFS))	• CANTAB Cognitive Assessments • Change in physical activity and sleep at home (digital wearable device (BioStamp))	NCT04739423	2	Recruiting
Bosutinib	Tyrosine kinase inhibitor	DLB (MoCA ≥ 18)	• Safety and tolerability Go/NoGo (25% discontinuations)	• Bosutinib levels in CSF and plasma • Changes in DLB-related CSF and plasma biomarkers (e.g., HVA, DOPAC, Abeta40/42, total tau, ptau231/181 and total and oligomeric alpha-synuclein)	NCT03888222	2	Active, not recruiting
Neflamapimod	p38 alpha kinase inhibitor	DLB (MMSE 15–28)	• Cogstate Neurological Test Battery (NTB)	• Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) • MMSE • NPI-10 • ISLT • Timed Up and Go Test (TUG) • Quantitative EEG	NCT04001517	2	Active, not recruiting

LBD Lewy body disease, DLB dementia with Lewy bodies, PD Parkinson disease, PDD Parkinson disease dementia, MOCA Montreal, Montreal Cognitive Assessment, MMSE Mini-Mental State Examination, CGIC Clinician’s Global Impression of Change, NPI Neuropsychological Inventory, UPDRS Unified Parkinson Disease Rating Scale, GDS Geriatric Depression Scale, EKG electrocardiogram, CIBIC-Plus Clinician Interview-Based Impression of Change plus Caregiver Input, CSF cerebrospinal fluid, MRI magnetic resonance imaging, ATP adenosine triphosphate, HVA homovanillic acid, DOPAC 3,4-dihydroxyphenylacetic acid, cGMP cyclic guanosine monophosphate, NMDA N-methyl-D-aspartate, CANTAB Cambridge Neuropsychological Test Automated Battery, EEG electroencephalogram, RBD rapid eye movement sleep behavior disorder