Efficacy of RGn600 in Patients With Mild-to-moderate Alzheimer's Disease

Study Overview
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Brief Summary
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This is a controlled investigation, with randomization of the patients, which aims at demonstrating the efficacy of device RGn600 in treating patients with mild-to-moderate Alzheimer's disease (AD). RGn600 is a non-invasive medical device which is applied on the head (helmet) and on the abdomen (abdominal belt). It combines 2 technologies: PhotoBioModulation (PBM), which involves exposure to light from the red to near-infrared wavelengths using lasers and Light Emitting Diodes (LEDs) Static Magnetic Stimulation (SMS), which consists in the application of a static magnetic field. Considering previous investigations, this innovative technology could reduce inflammation on the brain-gut axis, implicated in the development of Alzheimer's disease.

Detailed Description
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This multicentric investigation is planned to include 108 patients in France who will be followed up to 52 weeks. Patients meeting all eligibility criteria will be randomized on a 1: 1 ratio into one of the two following treatment groups: active RGn600 device or sham device (inactivated RGn600). The site investigation teams and patients/caregivers will be blinded. The device will be applied to the patients during 26 weeks through 20-min onsite sessions following the below pattern: 5 treatment sessions per week from Week 1 (W1) to W8 3 treatment sessions per week from W9 to W16 2 treatment sessions per week from W17 to W26 Throughout the investigation, patients will be treated per randomization with the device initially allocated by the IWRS. Follow-up will continue up to W52 ± 2 weeks At inclusion visit, after verification of the eligibility criteria, data regarding patients will be collected: demographic data, date of AD diagnosis, comorbidities, concomitant medications, sociological data. A blood sample for APOE genotyping will be also performed. Endpoints will be evaluated during 4 onsite visits at Day 0 (Inclusion, randomization to the active or sham group and first treatment session), W8 (last treatment session of), W26 (last treatment session of) and W52 ± 2 weeks. During these visits: Patient's cognition and autonomy will be assessed through neurological scales and/or neuropsychological tests Patient's quality of life and medico-economic interest of RGn600 treatment with regards to healthcare consumption will be assessed through questionnaires fulfilled by the patient himself/herself with the help of his/her caregiver The safety of RGn600 will be assessed : collection of all AEs and device deficiencies, blood samples for safety analysis, clinical exams Within the context of this investigation, a biobank will be created based on blood and fecal samples of patients included by Toulouse University Hospital Gerontopole site: Blood samples will be collected for all patients included by this site (at D0, W26 and W52) Fecal samples will be collected for the first 30 consecutive patients included by this site (at D0, W26 and W52). The biobank will be located at the site. The objective of this biobank will be to perform subsequent analysis on blood samples of AD blood markers. Other analyses might be conducted on blood and fecal samples as well such as Inflammatory blood markers (iAGE) and fecal microbiota and metabolome.

Official Title
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Efficacy of RGn600 in Patients With Mild-to-moderate Alzheimer's Disease: a Pivotal, Sham-controlled, Randomized, Double-blind, Multicentric Investigation (LIGHT4LIFE)

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Device: RGn600
* Device: RGn600 Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 55 to 85 years old (both included) Diagnosed with AD according to McKhann et al. international criteria dated 2011 With mild-to-moderate AD, i.e., 10 ≤ MMSE score ≤ 26 With blood analyses results (for: thyroid-stimulating hormone, vitamin B12, folate, complete blood count including platelets, electrolytes including calcium, creatinine, clearance, alanine aminotransferase, aspartate aminotransferase, bilirubin, coagulation, C-reactive protein) dated less than 1 year ago in line with AD diagnosis, as deemed by the investigator With brain Computed Tomography (CT) or/and Magnetic Resonance Imaging (MRI) scan dated less than 1 year ago in line with AD diagnosis, as deemed by the investigator In case of treatment with AD symptomatic treatments (memantine and acetylcholinesterase inhibitors) and psychotropic treatments (anxiolytics, antidepressants and neuroleptics): with a stable dose of such treatments 4 weeks before inclusion Who has a caregiver who is sufficiently and regularly present and can help the patient throughout the investigation, as deemed by the investigator Affiliated to French social security Who provided, with his/her caregiver, a dated and signed informed consent form. Exclusion Criteria: Patient protected by a French legal measure (sauvegarde de justice, tutelle or curatelle) Patient deprived of liberty or hospitalized without consent Non-menopausal woman Patient living in a medical facility Patient who experienced a surgery at the treatment application area (abdomen or head) within 3 months prior inclusion Patient with skin lesions on the treatment application area (abdomen or head) Patient with a short-term life-threatening pathology (e.g., evolving cancer; non-stable heart failure; severe hepatic, renal or respiratory failure, etc.) Patient diagnosed with a stroke within 3 months prior inclusion Patients with ferromagnetic material (i.e., iron, nickel, cobalt or any metal alloy) on or near the head or abdomen Patient with a risk of epileptic seizure Patient with a genetic form of AD Patient with major physical or neurosensorial disorders that may interfere with neurological assessments Patient with chronic psychosis or psychotic episodes Patient addicted to alcohol or drugs Patient with known and non-supplemented vitamin B12 and folic acid deficiencies Patient with known untreated hypothyroidism Patient who participated to another investigation/study involving the use of an investigational medical device/drug within the 30 days prior inclusion Patient not able to meet treatment sessions as deemed by the investigator Patient not able to complete requested investigation assessments as deemed by the investigator.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An interventional, prospective, multicentric, randomized, comparative and double-blinded pivotal clinical investigation
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active RGn600<br>RGn600 with a 10 Hz-pulsed wave mode light emission | Device: RGn600<br>* RGn600 with a 10 Hz-pulsed wave mode light emission<br>|
| Sham Comparator: Sham<br>Inactivated RGn600 | Device: RGn600 Sham<br>* RGn600 inactivated<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of patient's cognition between Day 0 and Week 26 as measured with the AD Assessment Scale-cognitive subscale (ADAS-cog) score | Absolute change (Week 26-Day 0) in ADAS-cog score | Day 0, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of patient's cognition from Day 0 to Week 8, from Day 0 to Week 52 and from Week 26 to Week 52 as measured with the AD Assessment Scale-cognitive subscale (ADAS-cog) score |  | Day 0, Week 8, Week 26, Week 52 | 
| Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's cognitive functions | Evolution of the score of the Mini Mental State Examination (MMSE) | Day 0, Week 26, Week 52 | 
| Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's cognitive functions | Evolution of the score of the Category Naming Test (CNT) | Day 0, Week 26, Week 52 | 
| Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's cognitive functions | Evolution of the scores of the Digit Symbol Substitution Test (DSST) | Day 0, Week 26, Week 52 | 
| Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's cognitive functions | Evolution of the score of the Trail Making Test part A and B (TMT A & B) | Day 0, Week 26, Week 52 | 
| Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's cognitive functions | Evolution of the score of the Clinical Dementia Rating - Sum of Boxes (CDR-SB) scale | Day 0, Week 26, Week 52 | 
| Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's cognitive functions | Evolution of the score of the AD Composite Score (ADCOMS) | Day 0, Week 26, Week 52 | 
| Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's cognitive functions | Evolution of the score of the Digit span test | Day 0, Week 26, Week 52 | 
| Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's autonomy | Evolution of the Instrumental Activities of Daily Living (IADL) questionnaire score | Day 0, Week 26, Week 52 | 
| Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's Overall clinical response | Evolution of the Clinical Global Impression (CGI) scale score | Day 0, Week 26, Week 52 | 
| Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's Quality of life | Evolution of the EuroQoL 5 Dimensions-5 Levels (EQ-5D-5L) score | Day 0, Week 26, Week 52 | 
| Incidence of Adverse Events (AEs) | Proportion of subjects with at least one Adverse Event (AE) | Throughout the investigation (from Day 0 to Week 52) | 
| Incidence of RGn600's Adverse Device Effects (ADEs) | Proportion of subjects with at least one Adverse Device Effect (ADE) | Throughout the investigation (from Day 0 to Week 52) | 
| Incidence of RGn600's Device Deficiencies (DDs) | Proportion of subjects with at least one Device Deficiency (DD) | Throughout the investigation (from Day 0 to Week 52) | 
| Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of level of safety blood markers | Change from baseline (Day 0) of level of Complete blood count, including platelets | Day 0, Week 8, Week 26, Week 52 | 
| Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of level of safety blood markers | Change from baseline (Day 0) of level of electrolytes, including calcium | Day 0, Week 8, Week 26, Week 52 | 
| Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of level of safety blood markers | Change from baseline (Day 0) of level of Creatinine | Day 0, Week 8, Week 26, Week 52 | 
| Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of level of safety blood markers | Change from baseline (Day 0) of level of creatinine clearance | Day 0, Week 8, Week 26, Week 52 | 
| Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of level of safety blood markers | Change from baseline (Day 0) of level of urea | Day 0, Week 8, Week 26, Week 52 | 
| Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of level of safety blood markers | Change from baseline (Day 0) of level of ASpartate AminoTransferase (ASAT) | Day 0, Week 8, Week 26, Week 52 | 
| Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of level of safety blood markers | Change from baseline (Day 0) of level of ALanine AminoTransferase (ALAT) | Day 0, Week 8, Week 26, Week 52 | 
| Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of level of safety blood markers | Change from baseline (Day 0) of level of Gamma-GT | Day 0, Week 8, Week 26, Week 52 | 
| Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of level of safety blood markers | Change from baseline (Day 0) of level of ALkalyne Phosphatase (ALP) | Day 0, Week 8, Week 26, Week 52 | 
| Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of level of safety blood markers | Change from baseline (Day 0) of level of bilirubin | Day 0, Week 8, Week 26, Week 52 | 
| Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of Blood pressure | Measure of Blood pressure (mmHg) | Day 0, Week 8, Week 26, Week 52 | 
| Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of Weight | Measure of Weight (Kg) | Day 0, Week 8, Week 26, Week 52 | 
| Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of Heart rate | Measure of Heart rate (beats/min) | Day 0, Week 8, Week 26, Week 52 | 
| Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of Temperature | Measure of Temperature (°C) | Day 0, Week 8, Week 26, Week 52 | 
| Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of ElectroCardioGram (ECG) interpretation | ElectroCardioGram (ECG) interpretation (Normal / Abnormal - Abnormality description) | Day 0, Week 8, Week 26, Week 52 | 
| Medico-economic interest of RGn600 treatment with regards to healthcare consumption | Resource Utilization in Dementia (RUD) questionnaire filled in by the patient/caregiver. | Day 0, Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer, Neurostimulation, Optics and photonics, Photobiomodulation, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Medical Device