REGEnLIFE RGn530 - Feasibility Pilot

REGEnLIFE RGn530 is a photobiomodulation medical device, consisting in a modular helmet and abdominal panel, composed of near-infrared low-level lasers (LLLT), near-infrared and red LEDs as well as a static magnetic field. RGn device application on both head and abdomen have demonstrated striking efficacy in preclinical studies. The investigator's results clearly indicated that RGn treatment produces a normalization of all parameters that are strongly modified in the model, including memory performances associated to oxidative stress, neuroinflammation or apoptosis markers, microbiota composition and specific markers related to the amyloid or tau processes (Blivet et al., Alzheimers Dement (NY), 2018).

Following such promising results, this pilot clinical study will evaluate the safety and efficacy of REGEnLIFE RGn530 device on cognitive performances evolution from mild-to-moderate Alzheimer's disease patients. The double-blind, randomized, monocentric sham-controlled clinical trial will be performed at the CHU de Montpellier. 64 patients will be enrolled: 32 in photobiomodulation group and 32 in sham group. Each patient will follow 8 weeks of treatment with 5 sessions of 25min per week (total of 40 sessions) and will undergo, for a total period of three months, series of clinical examinations including cognitive evaluation, biological and electrophysiological analyses, sleep recordings, and imaging assessments.

REGEnLIFE RGn530 medical device will follow EC labelling if proven to be safe and effective. In the light of anti-amyloid therapeutic approaches lack of success, RGn530 dual treatment is hoped to be particularly valuable as an innovative and extensive treatment strategy for AD.

Design : Prospective monocentric double-blind pilot study with 2 parallel groups of 32 patients. One with photobiomodulation (device set up and activated), the other with placebo-sham procedure (device set up but not activated). The study will consist of an inclusion visit (V0, D-30 to D-10), a photobiomodulation start visit (V1, D0), followed by 3 follow-up visits (V2 to D30, V3 to D60 and V4 to D90).

Dispositive : Photobiomodulation device developed by REGEnLIFE, RGn530 consisting of a modular helmet and an abdominal modular panel each comprising modules composed of low intensity infrared lasers (LLLT - Low Level Laser Therapy), infrared and red LEDs and a static magnetic field. The helmet and abdominal panel devices are connected to a steering console. Activation of the device will be done by personnel trained for this purpose by REGEnLIFE.

Originality and innovation : This study proposes to evaluate a new medical photobiomodulation device in the field of neurodegenerative diseases. These techniques have shown positive and promising results in the following areas: wound healing, pain management, inflammation, tissue regeneration, and the following disciplines: neuropsychiatry, dermatology and neurology.

Photobiomodulation is a technology of the same family as phototherapy, also called LLLT (Low Level Laser Therapy). It can be defined as the directional use of monochromatic or polychromatic light from low energy lasers and / or LEDs, in wavelengths included in the visible, infrared and near infrared, to modulate a function or induce a therapeutic effect in an athermal, non-invasive and non-destructive manner.

This pilot study aims to evaluate the efficacy and safety of this new non-invasive pre-marking device in patients with mild to moderate AD. To date, no study has been published with this device on this typology of patients.

Duration of treatment : 8 weeks with 5 sessions of 25 minutes per week, for a total of 40 sessions.

Study population : Patients with international AD diagnosis criteria according to McKhann et al., 2011 at mild to moderate stage (MMSE score between 16-26), having agreed and signed free and informed consent to participate in this study, without contraindications to the carrying out of the complementary investigations necessary for the evaluation of the efficiency and the tolerance of the RGn530.

Schedule of visits : Each patient will be followed for 3 months at the rate of 5 visits: inclusion V0 (D-10 to D-30), V1 (D0), V2 (M1), V3 (M2) and V4 (M3).

Number of patients : 64 patients will be included in this study: 32 in the photobiomodulation group and 32 in the placebo-sham group.

Duration of patient follow-up : Each patient will be followed for a total duration of 3 months with visits involving clinical, biological, electrophysiological, imaging, tests and questionnaires to assess the efficacy and tolerance of RGn530.

Eligibility Criteria:
Inclusion Criteria:

* Male and/or Female ;
* Age between 55-85 years old ;
* Diagnostic of AD according to international criteria of McKhann et al., 2011 \[1\] ;
* Mild-to-moderate Alzheimer's disease stage with MMSE score between 16 and 26 ;
* Symptomatic treatments specific to AD (Memantine, acetylcholinesterase inhibitors) and pyshotropic treatments (anxiolytics, anti-depressants, neuroleptics) are allowed but must be maintained at fixed doses during the 4 weeks previous to inclusion and during all the study length ;
* Patient approval for biological, eletrophysiological and imaging tests ;
* Enough availability to participate daily to the proposed treatment sessions ;
* Given informed, free consent, written and signed by participant and investigator (at the latest on the day of inclusion and before any examination needed for the research) ;
* Affiliated to social security regime or beneficiary of such a regime ;
* Patient given approval to perform a second lumbar puncture (without contraindication) if tests results and/or neurological follow-up need a CSF test for biomarkers ;

Exclusion Criteria:

* Exclusion criteria:
* Clinical and paraclinical details insufficient for AD diagnostic ;
* Genetic form of AD (genetic mutation characterized) ;
* No caregiver to complete neuropsychological scales and evaluation forms ;
* Patient living in a medical institution ;
* Illiteracy or inability to perform psycho-behavioral tests ;
* Physical or neurosensory problems susceptible to interfere with tests
* Contraindication or refusal to perform MRI imagerie examinations, PET-FDG, P300 and/or actimetry tests ;
* Patient carrying a pacemaker device or a ferromagnetic compound ;
* Short-term life-threatening pathologies (evolutive cancer, unstable cardiac failure, liver or kidney failure, severe respiratory insufficiency) ;
* Chronic psychosis or psychotic episodes ;
* Alcohol or drug addiction ;
* Epilpesy or other non-neurodegenerative diseases of the central nervous system ;
* Deficits in B12 and non-supplemented folic acid levels ;
* Untreated hypothyroidism ;
* Major skin lesions on treatment application regions (possibility to apply a bandage during the treatment if minor lesions) ;
* Recent major chirurgical intervention at the abdomen in the past three month before inclusion ;