Evaluating How Red-light Therapy Applied to the Head Affects Symptoms, Daily Life, and Brain Activity in People With Dementia With Lewy Bodies

Official title

Effect of Transcranial Photobiomodulation on Clinical Symptoms, Quality of Life and Cerebral Connectivity Modifications in Dementia With Lewy Bodies

Overview

Dementia with Lewy bodies (DLB) is a neurodegenerative disease diagnosed primarily based on the presence of cognitive decline, which may include difficulties with memory, attention, and more. Additionally, at least two of the following symptoms are needed for a probable diagnosis of DLB, and at least one for a possible DLB diagnosis (McKeith et al. 2017 and 2020): * Fluctuations in cognition, attention, and/or alertness * Visual hallucinations * Spontaneous parkinsonism * REM sleep behavior disorder Patients with DLB can experience cognitive deficits that can fluctuate and can vary for each patient. These may include deficits in memory, executive functions (planning and organizing), attention, visual processing, and language. This study aims to evaluate the effect of red-light therapy, delivered using a helmet that contains small LED lights, in patients with DLB. Participants' cognitive functions, clinical symptoms, quality of life and functional cerebral connectivity will be evaluated before starting therapy and again after three and six months of twice daily therapy use. As DLB also indirectly affects caregivers, the caregiver's quality of life and burden will also be evaluated before and at three and six months of therapy use by the participant. The study's inclusion period is 24 months and the duration of participation for each patient is 8 months (+/-10 days) maximum.

Detailed description

Dementia with Lewy bodies (DLB) is the second most frequent neurodegenerative disease after Alzheimer's disease and represents 15 to 20% of dementia cases (Ballard et al. 2001; Zaccai et al. 2005; Aarsland et al. 2008). DLB is diagnosed primarily based on the presence of cognitive decline, which is most often perceived as difficulties relating to attention, visuospatial capacities and executive functions like planning, decision making and more.

Additionally, at least two of the following core clinical symptoms are needed for a probable diagnosis of DLB, and at least one for a possible DLB diagnosis (McKeith et al. 2017 and 2020):

* Fluctuations in cognition, attention, and/or alertness * Visual hallucinations * Spontaneous parkinsonism * REM sleep behavior disorder

Suggestive symptoms may support the diagnosis of probable DLB when at least one core clinical symptom is present together with one of the following features, or possible DLB when one or more of the following features are present in the absence of any core clinical feature (McKeith et al. 2017 and 2020):

* Severe sensitivity to neuroleptics * Postural instability * Recurrent falls * Syncope or transient episodes of responsiveness * Severe autonomic dysfunction: constipation, urinary incontinence, etc. * Hallucinations in other sensory modalities (ex. auditory) * Delusions * Apathy, anxiety, depression * Reduced dopamine transporter uptake in basal ganglia on DAT scan * Abnormal cardiac I-MIBG scintigraphy (reduced myocardial MIBG uptake) * MRI or CT: relative preservation of medial temporal lobe structures * SPECT or PET: reduced tracer uptake with occipital hypometabolism * EEG: prominent posterior slow wave activity with periodic fluctuations in the pre-alpha/theta range

There is currently no treatment for DLB (Mueller et al. 2017). The effectiveness of available symptomatic treatments is also limited and sometimes accompanied by severe side effects (Boot et al. 2013; Boot, 2015). There is therefore an urgent need to develop therapeutic solutions adapted to DLB, aiming at neuroprotection and/or improvement of the quality of life of patients through better management of clinical symptoms. We are particularly interested in non-invasive and non-pharmacological approaches, with the aim of identifying methods without side effects and can easily be used by patients daily.

In this context, a new approach is the subject of growing interest within the medical and scientific communities, as well as the general public. Known as photobiomodulation (PBM), this technique involves applying red to infrared light (λ=600-1000nm) on biological tissues.

This study aims to evaluate the effect of transcranial PBM in patients with DLB.

Participants' cognitive functions, clinical symptoms, quality of life and cerebral connectivity will be evaluated before starting therapy and again after three and six months of twice daily therapy use. As DLB also indirectly affects caregivers, the caregiver's quality of life and burden will also be evaluated before and at three and six months of therapy use by the participant.

Interventions

• Device LUCIOLE CAP
  The LUCIOLE Cap is a medical device (without CE mark) designed for transcranial photobiomodulation (PBM). The cap was developed specifically for this purpose by the CLINATEC Endowment Fund (FDC), and it has not been used in any clinical investigation before. The LUCIOLE Cap will be used for the first time in this study with patients diagnosed with Dementia with Lewy bodies. The LUCIOLE cap is a non-invasive device that delivers PBM to the brain by shining light through the skin and bone. The LE
• Device LUCIOLE CAP (sham version)
  The CLINATEC Endowment Fund (FDC) designed this sham cap exclusively for scientific studies. It is built specifically to provide an accurate comparison against the active cap. This precise control allows investigators to clearly evaluate whether the active LUCIOLE cap delivers true, measurable benefits. The sham cap mimics the active LUCIOLE cap's operational characteristics and heat output without delivering actual PBM. The devices look identical and are distinguishable only by their serial nu

Primary outcome measures

• Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [Time frame: Measurements done right before start of PBM (at month 0 (M0)), after 3 months of PBM (M3), after six months of PBM (M6), and one month after end of PBM (M7)]

Eligibility criteria

Inclusion criteria

• Man or woman, 50 years or older
• Probable DLB diagnosed according to the criteria of McKeith et al., 2017, or the criteria of McKeith et al., 2020 for prodromal DLB
• Score on the Mini Mental State Examination (MMSE; Folstein et al., 1983) ≥ 18/30 at their last medical visit
• Good mastery of the French language
• Accompanied by a caregiver or a person able to provide information about them (interview, by telephone).
• Able to understand the objectives and risks associated with the research and to give informed consent, dated and signed
• Covered by a social health insurance plan
• Having a head circumference between 54 and 62 cm.

Exclusion criteria

• Not able to understand the objectives and risks related to research and to give informed consent
• Presence of another neurological disorder, including but not limited to brain tumors, stroke with potential cognitive impairment, or diagnosis of another progressive neurological disease (e.g., Alzheimer's disease, Parkinson's disease, etc.), and as determined by the investigator
• Having an MMSE score < 18 at the screening visit
• Unable to undergo a brain MRI due to medical reasons
• Participants whose follow-up would likely be disrupted during the study period (e.g., due to planned relocation or other reasons)
• Insufficient proficiency of the French language
• Participants experiencing an emergency of life-threatening situation
• Alone, without a caregiver present
• Participants presenting with a head/scalp injury
• Participants with a silicone allergy
• Participants with cranial/skull shape abnormalities
• Participants with a head circumference outside the range of 54-62 cm
• Participants requiring life support, continuous monitoring, and/or implanted medical devices (AIMD)
• Participants taking the antiepileptic Keppra (Levetiracetam)
• Participants whose anticholinesterase treatments have been changed within the past 2 months
• Participants whose antipsychotic treatments have been changed within the last 15 days
• Pregnant or breastfeeding women

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Supportive care

Study locations

France · 1 center

• Hôpitaux Universitaires de Strasbourg — Strasbourg

Identifiers

NCT: NCT07602296 · 9609

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗