Clinical Safety and Efficacy Evaluation of NanoLithium® NP03 in Patients With Mild-to-severe Alzheimer's Disease

NCT05423522 | Completed Phase 2

• 1 other identifier: 2021 NanoLi-CT01
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 8

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).

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• NPI-12 total score

  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.

  12 Weeks

Secondary Outcomes (34)

• Safety of treatment - Adverse effects

  approximately 1 year

• Safety of treatment - Clinical assessments - associated pathologies

  approximately 1 year

• Safety of treatment - Clinical assessments - biochemistry - AST/ALT

  approximately 1 year

• Safety of treatment - Clinical assessments - biochemistry - Creatinine

  approximately 1 year

• Safety of treatment - Clinical assessments - biochemistry - Glomerular filtration rate

  approximately 1 year

Study Arms (2)

NanoLithium® NP03

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

NanoLithium® NP03 DRUG

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.

NanoLithium® NP03

Placebo DRUG

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

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medesis Pharma SA: lead

Study Sites (8)

CHU de Lille

Lille, 59037, France

Location

CHU de Limoges - Hôpital Dupuytren

Limoges, 87042, France

Location

Hôpital De La Timone

Marseille, 13005, France

Location

CHU de Montpellier - Hôpital Gui de Chauliac

Montpellier, 34295, France

Location

Hôpital Lariboisière

Paris, 75010, France

Location

Hôpital Universitaire de Strasbourg

Strasbourg, 67000, France

Location

CHU Toulouse - Hôpital La Grave - Cité de la Santé

Toulouse, 31059, France

Location

Hôpital des Charpennes - Hospices Civils de Lyon

Villeurbanne, 69100, France

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Maria SOTO MARTIN, Prof.

  CHU Toulouse - Hôpital La Grave - Cité de la Santé

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind period followed by an open-label trial period. The double-blind will be maintained throughout the double-blind period treatment (except exceptional unblinding in emergency situations for reasons of patient safety).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 15, 2022
• First Posted: June 21, 2022
• Study Start: May 20, 2022
• Primary Completion: January 23, 2024
• Study Completion: October 29, 2024
• Last Updated: January 17, 2025

Record last verified: 2025-01

Locations

FR (8)