NanoLi®_AD: Clinical Safety and Efficacy Evaluation of NanoLithium® NP03 in Patients With Mild-to-severe Alzheimer's Disease
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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:
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NanoLithium® NP03 (N=34)
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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). |
Drug: NanoLithium® NP03
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.
|
| Placebo Comparator: 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. |
Drug: Placebo
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.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 - 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.
- 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 - 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 - 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 - 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
- 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_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_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 - MMSE Score [After 12 and 48 weeks]
MMSE score (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_PET-FDG [After 12 and 48 weeks]
Cerebral metabolic rate for glucose measured by Positron Emission Tomography-Fluorodeoxyglucose (PET-FDG).
- 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).
- Efficacy of treatment_Drug compliance [After 12 and 48 weeks]
Drug compliance by assessing the number of buccal deposits.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male and female patients between 50 and 90 years inclusive;
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Sufficient clinical and paraclinical information for the diagnosis of AD according to the international diagnosis criteria from McKhann G. M. et al. 2011;
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Patient presents clinically significant behavioral and psychological symptoms of dementia (BPSD) requiring medication in the opinion of the study physician;
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Mild to-severe AD with a Minimal Mental State Examination (MMSE) score from 10 to 26 included;
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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
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True abstinence [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception]
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Male patient must be willing to use male contraception (condom) during the study;
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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;
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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;
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Patient affiliated to French social security;
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Patient is willing to and can comply with the study protocol requirements, in the opinion of the investigator.
Exclusion Criteria:
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Patient with genetic form of AD (known genetic mutation);
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Patient with major physical or neurosensory problems likely to interfere with the tests; contraindication or refusal to perform functional brain imaging examinations;
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Absence of caregivers to complete psychological and behavioral scales and/or questionnaires;
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Patient with illiteracy and/or inability to perform psychological and behavioral evaluations;
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Pathologies involving short term vital prognosis (progressive cancer, unstable heart failure, severe liver, kidney or respiratory diseases);
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Primary chronic psychosis or psychotic episodes not associated with the AD pathology;
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Addiction to alcohol or drugs;
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Pregnancy or breast-feeding;
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Epilepsy or other neurodegenerative disorders;
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Vitamin B12 or folic acid deficiency without supplementation;
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Patient participating in another drug trial;
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Thyroid disorders not treated;
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Patient living in institution;
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Patient deprived of liberty by law;
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Patient with contraindications to drugs containing lithium: heart failure, renal failure, Addison disease, and Brugada syndrome.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CHU Toulouse - Hôpital La Grave - Cité de la Santé | Toulouse | France | 31059 |
Sponsors and Collaborators
- Medesis Pharma SA
Investigators
- Principal Investigator: Maria SOTO MARTIN, Prof., CHU Toulouse - Hôpital La Grave - Cité de la Santé
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2021 NanoLi-CT01