Background:
Alzheimer’s disease (AD) is the most frequent subtype of incurable neurodegenerative
dementias and its etiopathology is still not clearly elucidated.
Objective:
Outline the ongoing clinical trials (CTs) in the field of AD, in order to find novel master
regulators.
Methods:
We strictly reviewed all scientific reports from Clinicaltrials.gov and PubMed databases
from January 2010 to January 2019. The search terms were “Alzheimer's disease” or “dementia”
and “medicine” or “drug” or “treatment” and “clinical trials” and “interventions”. Manuscripts that
met the objective of this study were included for further evaluations.
Results:
Drug candidates have been categorized into two main groups including antibodies, peptides
or hormones (such as Ponezumab, Interferon β-1a, Solanezumab, Filgrastim, Levemir, Apidra,
and Estrogen), and naturally-derived ingredients or small molecules (such as Paracetamol,
Ginkgo, Escitalopram, Simvastatin, Cilostazo, and Ritalin-SR). The majority of natural candidates
acted as anti-inflammatory or/and anti-oxidant and antibodies exert their actions via increasing
amyloid-beta (Aβ) clearance or decreasing Tau aggregation. Among small molecules, most of
them that are present in the last phases act as specific antagonists (Suvorexant, Idalopirdine, Intepirdine,
Trazodone, Carvedilol, and Risperidone) or agonists (Dextromethorphan, Resveratrol, Brexpiprazole)
and frequently ameliorate cognitive dysfunctions.
Conclusion:
The presences of a small number of candidates in the last phase suggest that a large
number of candidates have had an undesirable side effect or were unable to pass essential eligibility
for future phases. Among successful treatment approaches, clearance of Aβ, recovery of cognitive
deficits, and control of acute neuroinflammation are widely chosen. It is predicted that some
FDA-approved drugs, such as Paracetamol, Risperidone, Escitalopram, Simvastatin, Cilostazoand,
and Ritalin-SR, could also be used in off-label ways for AD. This review improves our ability to
recognize novel treatments for AD and suggests approaches for the clinical trial design for this devastating
disease in the near future.
The Role of Futility Analyses in Alzheimer’s Disease Clinical Trials