Potential Therapeutic Strategies for Alzheimer’s Disease Targeting or Beyond β-Amyloid: Insights from Clinical Trials

Table 3

Other novel approaches in AD clinical trials.

Mechanism	RCT	Status	Estimated end	Dementia stage	Enrollment	Duration	Reported outcomes	Details of drugs/RCTS
Anti-inflammation and antioxidation	Curcumin	Phase 2; completed	2007.12	Mild-to-moderate	33			NSAID, cholesterol-lowering properties
	Etanercept	Phase 1; ongoing	2015.6	Mild-to-moderate	12	12 months	↑cognitive function with other nutrients.	Approved drug for arthritis; may modulate immune system; benefit AD patients
	dl-alpha-tocopherol (vitamin E)	Phase 3; completed	2012.10	Mild-to-moderate	613
	PUFA	Phase 1/2; ongoing*	2015.1		100	18 months		Tested alone or together with lipoic acid
	RO4602522	Phase 1; completed	2013.5		17
PDE inhibitors	PF-04447943	Phase 2, completed	2010.9	Mild-to-moderate	198			Selective PDE 9A inhibitor
	MK0952	Phase 2; completed	2007.11	Mild-to-moderate				Selective PDE 4 inhibitor
	Cilostazol	Phase 4; completed	2013.7	Mild-to-moderate	46			PDE3 inhibitor, Antiplatelet agent in WMHI; ↑pCREB
Tyrosine kinase inhibitor	Masitinib	Phase 3; ongoing*	2015.12	Mild-to-moderate	396			In combination with AChEI and/or memantine
Insulin and GLP1-R agonists	Intranasal insulin (glulisine)	Phase 2/3; ongoing	2015.2	MCI/mild AD	240	12 months
	Exendin-4 (exenatide)	Phase 2; ongoing	2016.7	MCI/early stage	100	3 years	Showed neuroprotection	Diabetes agent
	Liraglutide	Phase 2; ongoing	2017.1	early stage	206	12 months
Modulating mitochondrial function	AC-1204	Phase 2/3; ongoing	2015.1	Mild-to-moderate	480	26 weeks
	Latrepirdine (Dimebon)	Phase 3; completed	2009.12	Mild-to-moderate	598	6 months
RXR agonist	Bexarotene	Phase 2; ongoing	2014.3	Mild-to-moderate	20			Approved anticancer drug; linked to key pathways relevant to AD and Aβ
NGF delivery	CERE-110	Phase 2; ongoing	2014.12	Mild-to-moderate	50	24 months	24 months	Designed to help neurons function better; uses a virus to transfer NGF gene
	Encapsulated Cell biodelivery of NGF	Phase 1b	2011.12		6	12 months

RCT: randomized controlled trial; NSAID: nonsteroidal anti-inflammatory drugs; PDE: phosphodiesterase; WMHI: subcortical vascular disease; pCREB: phosphorylated cAMP-response element binding protein; AChEI: acetylcholinesterase inhibitor; GLP1-R: glucagon-likepeptide1 receptor; MCI: mild cognitive impairment; RXR: retinoid X receptors; NGF: nerve growth factor.
*RCTs with a combination of another drug.
Data sources: http://www.clinicaltrials.gov/.