Clinical trial NCT05423522: Clinical Safety and Efficacy Evaluation of NanoLithium® NP03 in Patients With Mild-to-severe Alzheimer's Disease
Official title: Prospective, Multicenter, First Part Randomized, Placebo-controlled, Parallel-group, Double-blind Period Followed by Open-label Trial Period to Evaluate Clinical Safety & Efficacy of NanoLithium® NP03 in Patients With Mild-to-severe Alzheimer's Disease: Proof-of-concept Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Lead sponsor: Medesis Pharma SA
Sponsor class: INDUSTRY
First posted: 2022-06-21
Enrollment: 72
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A prospective, multicenter, with a first randomized, placebo-controlled, parallel-group, double-blind period followed by an open-label trial period to evaluate the clinical safety and efficacy of NanoLithium® NP03 in patients with mild-to-severe Alzheimer's disease: a proof-of-concept study.
Primary purpose: TREATMENT

Brief 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).

Detailed description: 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.

Primary outcomes:
measure: NPI-12 total score
timeFrame: 12 Weeks
Secondary outcomes:
measure: Safety of treatment - Adverse effects
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - associated pathologies
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - biochemistry - AST/ALT
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - biochemistry - Creatinine
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - biochemistry - Glomerular filtration rate
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - biochemistry - B9 vitamin
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - biochemistry - B12 vitamin
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - biochemistry - T3
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - biochemistry - T4
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - biochemistry - TSH
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - Hematology
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - Lithium blood level
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - Systolic and diastolic blood pressure
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - Pulse rate
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - ECG - PR
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - ECG - QRS
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - ECG - QT
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - ECG - RR
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - ECG - QTcB
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - Weight
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - Height
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - BMI
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - cognitive signs
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - focal neurological signs
timeFrame: approximately 1 year
measure: Safety of treatment - Clinical assessments - motricity
timeFrame: approximately 1 year
measure: Efficacy of treatment_BPSD_NPI-C-IPA
timeFrame: After 12 and 48 weeks
measure: Efficacy of treatment_BPSD_NPI-12
timeFrame: After 12 and 48 weeks
measure: Efficacy of treatment_cognitive performances - MMSE Score
timeFrame: After 12 and 48 weeks
measure: Efficacy of treatment_cognitive performances - CDRS Score
timeFrame: After 12 and 48 weeks
measure: Efficacy of treatment_cognitive performances - ADL Score
timeFrame: After 12 and 48 weeks
measure: Efficacy of treatment_PET-FDG
timeFrame: After 12 and 48 weeks
measure: Efficacy of treatment_Biomarkers_Peripheral biomarkers
timeFrame: After 12 and 48 weeks
measure: Efficacy of treatment_Biomarkers_Non-specific biomarkers
timeFrame: After 12 and 48 weeks
measure: Efficacy of treatment_Drug compliance
timeFrame: After 12 and 48 weeks
Other outcomes:
Locations:
city: Lille
country: France
facility: CHU de Lille
city: Limoges
country: France
facility: CHU de Limoges - Hôpital Dupuytren
city: Marseille
country: France
facility: Hôpital De La Timone
city: Montpellier
country: France
facility: CHU de Montpellier - Hôpital Gui de Chauliac
city: Paris
country: France
facility: Hôpital Lariboisière
city: Strasbourg
country: France
facility: Hôpital Universitaire de Strasbourg
city: Toulouse
country: France
facility: CHU Toulouse - Hôpital La Grave - Cité de la Santé
city: Villeurbanne
country: France
facility: Hôpital des Charpennes - Hospices Civils de Lyon
Study officials:
affiliation: CHU Toulouse - Hôpital La Grave - Cité de la Santé
name: Maria SOTO MARTIN, Prof.
role: PRINCIPAL_INVESTIGATOR
References: