Clinical trial NCT05926011: Efficacy of RGn600 in Patients With Mild-to-moderate Alzheimer's Disease
Official title: Efficacy of RGn600 in Patients With Mild-to-moderate Alzheimer's Disease: a Pivotal, Sham-controlled, Randomized, Double-blind, Multicentric Investigation (LIGHT4LIFE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alzheimer Disease
Keywords: Alzheimer
Neurostimulation
Optics and photonics
Photobiomodulation
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Medical Device
Lead sponsor: REGEnLIFE SAS
Sponsor class: INDUSTRY
Collaborators: name: RCTs
name: University Hospital, Toulouse
First posted: 2023-07-03
Enrollment: 108
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An interventional, prospective, multicentric, randomized, comparative and double-blinded pivotal clinical investigation
Primary purpose: TREATMENT

Brief summary: 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: 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, fecal and saliva 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).
* Saliva samples will be collected for the patients included by this site after the substantial modification approval (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, fecal and saliva samples as well such as Inflammatory blood markers (iAGE), fecal microbiota and metabolome and salivary micro RiboNucleic Acid (microRNAs)

Eligibility criteria: 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 taking a disease-modifying treatment such as the Leqembi® or any other disease-modifying treatment that may be authorized in France before the end of the study
* 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, or implanted with a pacemaker
* 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.

Primary outcomes:
measure: Evolution of patient's cognition between Day 0 and Week 26 as measured with the AD Assessment Scale-cognitive subscale (ADAS-cog) score
timeFrame: Day 0, Week 26
Secondary outcomes:
measure: 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
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's cognitive functions
timeFrame: Day 0, Week 26, Week 52
measure: Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's cognitive functions
timeFrame: Day 0, Week 26, Week 52
measure: Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's cognitive functions
timeFrame: Day 0, Week 26, Week 52
measure: Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's cognitive functions
timeFrame: Day 0, Week 26, Week 52
measure: Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's cognitive functions
timeFrame: Day 0, Week 26, Week 52
measure: Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's cognitive functions
timeFrame: Day 0, Week 26, Week 52
measure: Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's cognitive functions
timeFrame: Day 0, Week 26, Week 52
measure: Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's autonomy
timeFrame: Day 0, Week 26, Week 52
measure: Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's Overall clinical response
timeFrame: Day 0, Week 26, Week 52
measure: Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's Quality of life
timeFrame: Day 0, Week 26, Week 52
measure: Incidence of Adverse Events (AEs)
timeFrame: Throughout the investigation (from Day 0 to Week 52)
measure: Incidence of RGn600's Adverse Device Effects (ADEs)
timeFrame: Throughout the investigation (from Day 0 to Week 52)
measure: Incidence of RGn600's Device Deficiencies (DDs)
timeFrame: Throughout the investigation (from Day 0 to Week 52)
measure: 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
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: 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
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: 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
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: 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
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: 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
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: 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
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: 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
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: 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
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: 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
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: 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
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of Blood pressure
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of Weight
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of Heart rate
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of Temperature
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: Evolution from Day 0 to Week 8, Day 0 to Week 26 and from Day 0 to Week 52 of ElectroCardioGram (ECG) interpretation
timeFrame: Day 0, Week 8, Week 26, Week 52
measure: Medico-economic interest of RGn600 treatment with regards to healthcare consumption
timeFrame: Day 0, Week 26
Other outcomes:
measure: [Exploratory endpoint from biobanking] Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's AD blood markers
timeFrame: Day 0, Week 26, Week 52
measure: [Exploratory endpoint from biobanking] Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's AD blood markers
timeFrame: Day 0, Week 26, Week 52
measure: [Exploratory endpoint from biobanking] Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's AD blood markers
timeFrame: Day 0, Week 26, Week 52
measure: [Exploratory endpoint from biobanking] Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's AD blood markers
timeFrame: Day 0, Week 26, Week 52
measure: [Exploratory endpoint from biobanking] Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's microbiota
timeFrame: Day 0, Week 26, Week 52
measure: [Exploratory endpoint from biobanking] Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's metabolome
timeFrame: Day 0, Week 26, Week 52
measure: [Exploratory endpoint from biobanking] Evolution from Day 0 to Week 26 and from Day 0 to Week 52 of patient's AD saliva markers
timeFrame: Day 0, Week 26, Week 52
Locations:
city: Castres
country: France
facility: CHIC Castres Mazamet Site Autan
city: Lavaur
country: France
facility: CH Lavaur
city: Paris
country: France
facility: Hôpital Lariboisière
city: Paris
country: France
facility: Hôpital Broca
city: Timone
country: France
facility: Hôpital de la Timone,
city: Toulouse
country: France
facility: Toulouse University Hospital Gerontopole
Study officials:
affiliation: REGEnLIFE SAS
name: Guillaume BLIVET
role: STUDY_DIRECTOR
affiliation: Montpellier University
name: Jacques TOUCHON
role: STUDY_CHAIR
affiliation: Toulouse University Hospital Gerontopole
name: Julien DELRIEU
role: PRINCIPAL_INVESTIGATOR
References: