Table 4:

Examples of clinical trials assessing treatment interventions in patients with Lewy body dementia

	NCT number	Study design	Proposed mechanism of action	Main outcomes	Comment
Intepirdine (RVT-101)	, , and	Double-blind, randomised, placebo-controlled study of RVT-101 in patients with dementia with Lewy bodies () and a double-blind randomised placebo-controlled study of gait impairment in patients with either Alzheimer’s disease, dementia with Lewy bodies, or Parkinson’s disease (); additionally, there was a planned 6 month extension study with RVT-101 in patients with dementia with Lewy body ()	Serotonin 6 receptor antagonist that causes the release of acetylcholine and other neurotransmitters	Primary outcome for first study () was Unified Parkinson’s Disease Rating Scale-Part III and, for the second study (), quantitative gait function; secondary outcomes included cognitive and Clinician’s Interview-Based Impression of Change score Plus Caregiver Input () and safety outcomes ()	, , and were terminated in 2018. The results indicated a lack of efficacy on all outcomes for . No formal results have been posted for and
Nelotanserin	, , and	Double-blind, randomised, placebo-controlled cross-over study in patients with Lewy body dementia with visual hallucinations () and a double-blind, randomised, placebo-controlled parallel-arm study in patients with dementia with Lewy bodies or Parkinson’s disease dementia who have REM sleep behaviour disorder (); additionally, an open-label study was planned in patients with Lewy body dementia with frequent visual hallucinations or REM Sleep Behavior Disorder ()	Serotonin receptor subtype 5-HT2A inverse agonist	Visual hallucinations and safety data as well as motor function in first trial (), and REM sleep behaviour disorder symptoms in the second ()	No formal results from these trials have been posted or published but further development of this drug has been discontinued
SYN120		Double-blind randomised placebo-controlled study in patients with Parkinson’s disease dementia	Dual HT2A with a dual 5-HT6 or 5-HT5 antagonist	Primary outcomes were attention measures	Results posted (May 2019) to clinicaltrials.gov indicated a lack of statistical difference on primary outcomes between active and placebo arms
LY3154207		Double-blind randomised placebo-controlled study in patients with Parkinson’s disease dementia	Enhancer of dopamine receptor D1	Attention measures (primary) and cognitive, neuropsychiatric outcomes, sleep, motor, and functional measures (secondary)	Recruiting
E2027		Double-blind randomised placebo-controlled study of patients with dementia with Lewy Bodies	A selective phosphodiesterase 9 inhibitor that might maintain cyclic GMP concentration in the brain	Cognitive measures and Global Impression of Change scores with wide range of secondary outcomes including, for example, neuropsychiatric, cognitive fluctuations, global impression of change, and safety data	Recruiting
Ambroxol		Double-blind randomised placebo-controlled parallel study in patients with Parkinson’s disease dementia	Raises the concentrations of the enzyme β-glucocerebrosidase, which might lead to reduced concentrations of α-synuclein	Cognitive measures and Global Impression of Change scores with wide range of secondary outcomes including, for example, motor performance measures, cerebrospinal fluid concentrations of α-synuclein, tau, phospho-tau and β amyloid 42 and structural magnetic resonance biomarkers (ventricular volumes and hippocampal atrophy)	Recruiting
Deep brain stimulation	and	Pilot studies assessing stimulation of the nucleus basalis of Meynert in patients with dementia with Lewy bodies	Enhance cholinergic output of the nucleus basalis of Meynert	Various cognitive and neuropsychiatric outcomes	Completed: awaiting results
HTL0018318		Double-blind randomised placebo-controlled trial of patients with dementia with Lewy bodies	Muscarinic M1 agonist	Primary outcome was to assess safety and secondary outcomes included measures of cognition and psychosis	Trial suspended pending investigation of an unexpected animal toxicology finding (development of tumours)
Ramelteon	and	Double blind, randomised placebo-controlled pilot studies for REM sleep behaviour disorder which included patients with dementia with Lewy body	Selective agonist of melatonin receptors (MT1 and MT2)	Primary outcomes included sleep efficiency and other sleep parameters with a wide range of secondary outcomes (motor, cognitive, and functional etc)	Trials terminated due to low participant enrolment and recruitment
Pimavanserin		Double-blind randomised placebo-controlled trial for the treatment of hallucinations and delusions associated with dementia related psychosis; it will include patients with dementia with Lewy bodies or Parkinson’s disease dementia	Selective 5-HT2A inverse agonist	Time to relapse in double blind period or discontinuation for any reason	Recruiting
Bosutinib		Double blind randomised placebo-controlled study in dementia with Lewy bodies	Tyrosine kinase inhibitor targeting c-Abelson and Src tyrosine kinases. In models of neurodegeneration, it reduces alpha-synuclein, tau, and amyloid β	Primary outcome is safety with secondary outcomes including cerebrospinal fluid markers of, for example, bosutinib levels, cell death, tau, phosphorylated tau, amyloid β, and inflammation	Recruiting

REM=rapid eye movement.