Clinical Safety and Efficacy Evaluation of NanoLithium® NP03 in Patients With Mild-to-severe Alzheimer's Disease
- Registration Number
- NCT05423522
- Lead Sponsor
- Medesis Pharma SA
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 72
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Description: Homogeneous yellow oily liquid. Dosage: One administration of 3 mL per day (1.8 mg/day) by depositing 1.5 mL in the gingivo-jugal groove of each cheek with the graduated pipette. Duration of treatment: 12 weeks during the double-blind period. NanoLithium® NP03 NanoLithium® NP03 Description: Homogeneous yellow oily liquid. Dosage: One administration of 3 mL per day (1.8 mg/day) by depositing 1.5 mL in the gingivo-jugal groove of each cheek with the graduated pipette. Duration of treatment: Approximately one year (12 weeks for the double-blind period and 36 weeks for the subsequent open-label period).
- Primary Outcome Measures
Name Time Method NPI-12 total score 12 Weeks The change from baseline to end of double-blind period (W12) of the NPI-12 total score in the NanoLithium® NP03 arm and in the placebo arm.
- Secondary Outcome Measures
Name Time Method Safety of treatment - Clinical assessments - Weight approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: General clinical examination: weight (in Kg)
Safety of treatment - Clinical assessments - Height approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: General clinical examination: height (in cm)
Safety of treatment - Clinical assessments - BMI approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: General clinical examination: body mass index (BMI) (weight and height will be combined to report BMI in kg/m\^2)
Safety of treatment - Clinical assessments - cognitive signs approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common neurological assessments: Neurological clinical examination: cognitive signs: questions asked to patients/caregiver to detect execution troubles, attention troubles, language, gnosic troubles, praxis, visuo-spacial troubles and temporo-spacial orientation
Efficacy of treatment_BPSD_NPI-C-IPA After 12 and 48 weeks To assess the BPSD at 12 and 48 weeks, change from baseline to week 12 and week 48 on the Neuropsychiatric Inventory - Clinician items mapped to International Psychogeriatric Association (NPI-C-IPA) scale (Units on a Scale).
Efficacy of treatment_Biomarkers_Peripheral biomarkers After 12 and 48 weeks Pathophysiological peripheral biomarkers (amyloid biomarkers, neurofilaments, Tau protein, BDNF) (pg/ml).
Efficacy of treatment_Biomarkers_Non-specific biomarkers After 12 and 48 weeks Non-specific biomarkers (inflammation cytokines).
Safety of treatment - Clinical assessments - associated pathologies approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: associated pathologies: medical conditions start and end date or ongoing, currently treated or not, recorded from patients file.
Efficacy of treatment_PET-FDG After 12 and 48 weeks Cerebral metabolic rate for glucose measured by Positron Emission Tomography-Fluorodeoxyglucose (PET-FDG).
Safety of treatment - Adverse effects approximately 1 year The number and types of adverse effects during the study and causal role of the study treatment.
Safety of treatment - Clinical assessments - biochemistry - B9 vitamin approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: B9 vitamin (µg/L or nmol/L)
Safety of treatment - Clinical assessments - biochemistry - AST/ALT approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: AST/ALT (UI/L)
Safety of treatment - Clinical assessments - biochemistry - Creatinine approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: Creatinine (mg/L or µmol/L)
Safety of treatment - Clinical assessments - biochemistry - Glomerular filtration rate approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: Glomerular filtration rate -Cockcroft or MDRD method - (ml/min/1,73m2)
Safety of treatment - Clinical assessments - biochemistry - B12 vitamin approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: B12 vitamin (ng/L or pmol/L)
Safety of treatment - Clinical assessments - biochemistry - T3 approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: T3 (µg/L or nmol/L)
Safety of treatment - Clinical assessments - biochemistry - T4 approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: T4 (µg/L or nmol/L)
Safety of treatment - Clinical assessments - biochemistry - TSH approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: TSH (mlU/L)
Safety of treatment - Clinical assessments - Hematology approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: hematology
Safety of treatment - Clinical assessments - Lithium blood level approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: lithium blood level
Safety of treatment - Clinical assessments - Systolic and diastolic blood pressure approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: Vital signs: Systolic and diastolic blood pressure (mm Hg)
Safety of treatment - Clinical assessments - Pulse rate approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: Vital signs: Pulse rate (beats per minute \[bpm\])
Safety of treatment - Clinical assessments - ECG - PR approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: Electrocardiogram (ECG): PR interval (msec)
Safety of treatment - Clinical assessments - ECG - QRS approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: Electrocardiogram (ECG): QRS interval (msec)
Safety of treatment - Clinical assessments - ECG - QT approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: Electrocardiogram (ECG): QT interval (msec)
Safety of treatment - Clinical assessments - ECG - RR approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: Electrocardiogram (ECG): RR interval (msec)
Safety of treatment - Clinical assessments - ECG - QTcB approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: Electrocardiogram (ECG): QTcB interval (msec)
Safety of treatment - Clinical assessments - focal neurological signs approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common neurological assessments: Neurological clinical examination: focal neurological signs: questions asked to patients/caregiver to detect extrapyramidal syndrome, pyramidal syndrome, cerebellar syndrome, frontal syndrome, hallucinations, dysautonomia, sensitive system and epilepsy
Safety of treatment - Clinical assessments - motricity approximately 1 year To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common neurological assessments: Neurological clinical examination: motricity: questions asked to patients/caregiver to detect muscular tonus, abnormal movements, reflex, walking troubles, falls, postural troubles, coordination, sphincter and trophic troubles
Efficacy of treatment_cognitive performances - MMSE Score After 12 and 48 weeks MMSE score (Units on a Scale).
Efficacy of treatment_BPSD_NPI-12 After 12 and 48 weeks To assess the BPSD at 12 and 48 weeks, score of each item of the Neuropsychiatric Inventory (NPI-12) (Units on a Scale).
Efficacy of treatment_cognitive performances - CDRS Score After 12 and 48 weeks Clinical Dementia Rating Scale (CDRS) score (Units on a Scale).
Efficacy of treatment_cognitive performances - ADL Score After 12 and 48 weeks Activity of Daily Living (ADL) score (Units on a Scale).
Efficacy of treatment_Drug compliance After 12 and 48 weeks Drug compliance by assessing the number of buccal deposits.
Trial Locations
- Locations (8)
CHU de Lille
🇫🇷Lille, France
CHU de Limoges - Hôpital Dupuytren
🇫🇷Limoges, France
Hôpital De La Timone
🇫🇷Marseille, France
CHU de Montpellier - Hôpital Gui de Chauliac
🇫🇷Montpellier, France
Hôpital Lariboisière
🇫🇷Paris, France
Hôpital Universitaire de Strasbourg
🇫🇷Strasbourg, France
CHU Toulouse - Hôpital La Grave - Cité de la Santé
🇫🇷Toulouse, France
Hôpital des Charpennes - Hospices Civils de Lyon
🇫🇷Villeurbanne, France