clinical safety and efficacy evaluation of nanolithium® np03 in patients with mild-to-severe alzheimer's disease

Conditions: Alzheimer's Disease

Summary: this proof-of-concept study will assess safety, tolerance, and efficacy of nanolithium® np03 in patients with mild-to-severe alzheimer's disease (ad).

this french study is a prospective, multicenter, randomized (1:1), placebo-controlled, parallel-group, double-blind period followed by an open-label trial period to evaluate clinical safety and efficacy of nanolithium® np03 in patients with mild-to-severe alzheimer's disease. patients will be randomized into two treatment arms: * nanolithium® np03 (n=34) * placebo (n=34) the first phase will consist of a double blind 12-week -period, which will be followed by an open-label 36-week period for each arm. a total of 18 clinical or phone call visits are scheduled during this study. during the follow-up, clinical, biological, electrophysiological, imaging assessments and questionnaires will be performed to determine the safety, efficacy, and disease-modifying effect of nanolithium® np03.

Eligibility criteria:
inclusion criteria: * male and female patients between 50 and 90 years inclusive; * sufficient clinical and paraclinical information for the diagnosis of ad according to the international diagnosis criteria from mckhann g. m. et al. 2011; * patient presents clinically significant behavioral and psychological symptoms of dementia (bpsd) requiring medication in the opinion of the study physician (at least one item of the neuropsychiatric inventory-12 \[npi-12\] with a score ≥ 4); * mild to-severe ad with a minimal mental state examination (mmse) score from 10 to 26 included; * symptomatic treatments of ad (acetylcholinesterase inhibitors and memantine) and psychotics drugs (benzodiazepines, antidepressants, anxiolytics, neuroleptics) are allowed but need to be maintained during at least 4 weeks before inclusion and during the follow-up; * female patient of childbearing potential must be willing to use an efficient birth control method during the study and until 5 days after the end of the treatment. a woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus, tubal ligation). the following are acceptable contraceptive methods: - established use of oral, injected, or implanted hormonal methods of contraception - intrauterine system or placement of an intrauterine device - double barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam, gel, film, cream, or suppository - true abstinence \[periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception\] * male patient must be willing to use male contraception (condom) during the study; * patient must have availability of a person ("study partner" or caregiver) who has frequent and sufficient contact with the patient, can provide accurate information regarding the patient's behavior, cognitive, and functional abilities as well as his/her health throughout the study, and agrees to provide information at investigational site visits; * patient is willing and able to give informed consent. if the study patient is not competent, a legally authorized representative must provide informed consent on his/her behalf, and the patient must provide assent; * patient affiliated to french social security; * patient is willing to and can comply with the study protocol requirements, in the opinion of the investigator. * if the patient took part to another therapeutic clinical trial, he/she must systematically observe a wash-out period of \> 4 weeks, or of \> 6 months if he/she received a biologic disease modifying treatment (antibodies targeting the β-amyloid protein or the p-tau protein) or 5 half-lives of investigational drug(s), whichever is longer. exclusion criteria: * patient with genetic form of ad (known genetic mutation); * patient with major physical or neurosensory problems likely to interfere with the tests; contraindication or refusal to perform functional brain imaging examinations; * absence of caregivers to complete psychological and behavioral scales and/or questionnaires; * patient with illiteracy and/or inability to perform psychological and behavioral evaluations; * pathologies involving short term vital prognosis (progressive cancer, unstable heart failure, severe liver, kidney or respiratory diseases); * primary chronic psychosis or psychotic episodes not associated with the ad pathology; * addiction to alcohol or drugs; * pregnancy or breast-feeding; * epilepsy or other neurodegenerative disorders; * vitamin b12 or folic acid deficiency without supplementation; * patient participating in another drug trial; * thyroid disorders not treated; * patient living in institution; * patient deprived of liberty by law; * patient with contraindications to drugs containing lithium: heart failure, renal failure, addison disease, and brugada syndrome.