Development and Evaluation of Computerized Olfactory Training Program for Cognitive Decline in Early Alzheimer's Disease

EvOn Medics

Status and phase: Unknown; Phase 2

Conditions: Mild Cognitive Impairment; Memory Impairment; Early Alzheimer's Disease

Treatments: Drug: COT; Drug: Sham

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT05122598

2R44AG061981-03 (U.S. NIH Grant/Contract)

COTAG061981

Details and patient eligibility

About

The purpose of this study is to determine whether daily treatment with this new treatment approach, called COT would be effective in protecting the memory and brain regions of people who are already showing signs of memory loss.

Full description

Alzheimer's disease process starts in parts of the brain used for perceiving and interpreting smell many years before people begin to lose their memory and other cognitive functions. These parts of the brain are called the "olfactory regions." From these olfactory regions, Alzheimer's disease spread to involve other parts of the brain. Scientists have shown that stimulating the olfactory regions through exposure to multiple naturally occurring essential or plant oils help to reduce the brain changes of Alzheimer's disease in animals. Also, many components from these plant oils have been shown to protect nerve cells from various kinds of stress and injuries; and we say they are 'neuroprotective'. A novel home-based olfactory chemosensory stimulation program that uses a portable, programmed, device known as the Computerized Olfactory Training (COT) program, administers olfactory psychophysical tasks while patients are being stimulated repeatedly with neuroprotective olfactory stimulants, using neuroscience-guided stimulation parameters to ensure sustained activation of all primary and secondary olfactory structures.

Enrollment: 200 estimated patients

Sex: All

Ages: 55 to 95 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age 55-95 years; female must be post-menopausal for ≥ 2 consecutive years
2. Probable mild AD according to the core clinical criteria outlined in the National Institute on Aging/Alzheimer's Association (NIA-AA) Guidelines
3. MMSE score between the range of 21 to 27; CDR score of 1.0 (mild AD); scores on Logical Memory II subscale (Delayed Recall) from the Wechsler Memory Scale-Revised (WMS) within the recommended education-adjusted ranges
4. Have either cerebrospinal fluid (CSF) Aβ42 levels that are consistent with Alzheimer's disease as measured via mass spectrometry by C2N, or document elevated amyloid burden consistent with Alzheimer's disease from positron emission tomography (PET) imaging
5. Screening MRI without evidence of infection, infarction, or other focal lesions of neurological disease; and no significant nasal disease.
6. All participants must have a study partner with normal cognitive function.

Exclusion criteria

1. Any significant neurologic disease
2. Major psychiatric disorder within the past 2 years
3. Substance use disorder within the past 2 years
4. Any unstable medical condition
5. Contraindications to MRI
6. Any Alzheimer's disease modifying therapy (DMT) in the past 6 months
7. Antipsychotics, anticholinergics, anticonvulsants, and other antidepressants, benzodiazepines, or other psychotropic medications and blood thinners, except for aspirin at a prophylactic dose or less.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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200 participants in 2 patient groups

Computerized Olfactory Training (COT) Device with olfactory stimulants

Active Comparator group

Description:

COT device with olfactory stimulants consists of daily 40 cycles of intervention with a combination of olfactory stimulation and training tasks, lasting \~45 minutes, delivered once daily over 6 months period by the participant or their partner/caregiver.

Treatment:

Drug: COT

Sham/COT Device

Sham Comparator group

Description:

This is COT device that uses compressed room air scented with phenylethylamine (rose scent) instead of olfactory stimulants and has shape pattern matching tasks instead of cognitive tasks, in order to blind users to their treatment assignment. Similar to the COT, sham COT will be used daily for 45 minutes.

Treatment:

Drug: Sham