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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Mild Cognitive Impairment; Memory Impairment; Early Alzheimer's Disease
• Intervention / Treatment: Drug: COT; Drug: Sham

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Evaristus Nwulia, MD; Phone Number: 410-227-2005; Email: enwulia@evonmedics.org
• Study Contact Backup: Name: Maria Hipolito, MD; Phone Number: 571-241-2766; Email: mhipolito@evonmedics.org

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20002
      • Recruiting
      • Clinics of Dr. Edwin Chapman @ MHDG
      • Contact: Edwin Chapman, MD; Phone Number: 202-396-8550; Email: echap1647@aol.com
    • Washington, District of Columbia, United States, 20020
      • Recruiting
      • Family and Medical Counseling Service, Inc
      • Contact: Michael Serlin, MD; Phone Number: 573 202-889-7900; Email: mserlin@fmcsinc.org]
    • Washington, District of Columbia, United States, 20060
      • Recruiting
      • Howard University (HU)
      • Contact: Thomas O Obisesan, MD; Phone Number: 202-865-6100; Email: tobisesan@howard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Computerized Olfactory Training (COT) Device with olfactory stimulants; 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.	Drug: COT; The COT with proprietary odorant molecules is designed to stimulate olfactory neural activity over long periods of time combined with orbitofrontal cortex (OFC) dependent olfactory tasks.; Other Names: COT with olfactory stimulants
Sham Comparator: Sham/COT Device; 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.	Drug: Sham; Sham COT uses artificially scented compressed room air instead of olfactory stimulants and has control cognitive olfactory tasks.; Other Names: Sham COT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Logical Memory II subscale (Delayed Paragraph Recall)	Measures patient's ability to recall information after a 20 to 30 minutes delay for story b from the Wechsler Memory Scale-IV (0-25). Higher scores indicate better performance. This is use for evaluation of forgetting or memory decay.	Baseline
Logical Memory II subscale (Delayed Paragraph Recall)	Measures patient's ability to recall information after a 20 to 30 minutes delay for story b from the Wechsler Memory Scale-IV (0-25). Higher scores indicate better performance. This is use for evaluation of forgetting or memory decay.	6 months
Logical Memory II subscale (Delayed Paragraph Recall)	Measures patient's ability to recall information after a 20 to 30 minutes delay for story b from the Wechsler Memory Scale-IV (0-25). Higher scores indicate better performance. This is use for evaluation of forgetting or memory decay.	9 months
ADCS-PACC composite score	Combines tests that assess episodic memory, timed executive function and global cognition. Alzheimer's Disease Cooperative Study (ADCS) PACC (ADAS-PACC) is a composite score of: The Total Recall score from the Free and Cued Selective Reminding Test (FCSRT) (range from 0-48 points), The Delayed Recall score on the Logical Memory IIa subtest from the Wechsler Memory Scale (range from 0-25 points), the Digit Symbol Substitution Test score from the Wechsler Adult Intelligence Scale-Revised (range from 0-93 points), and the MMSE score (range from 0-30 points). Each of the component change scores is divided by the baseline sample standard deviation of that component, to form standardized z scores. These z scores are summed to form the composite. Z Scores could range from -5 to +5 with higher scores indicating less deficit and lower scores indicating greater deficit.	Baseline
ADCS-PACC composite score	Combines tests that assess episodic memory, timed executive function and global cognition. Alzheimer's Disease Cooperative Study (ADCS) PACC (ADAS-PACC) is a composite score of: The Total Recall score from the Free and Cued Selective Reminding Test (FCSRT) (range from 0-48 points), The Delayed Recall score on the Logical Memory IIa subtest from the Wechsler Memory Scale (range from 0-25 points), the Digit Symbol Substitution Test score from the Wechsler Adult Intelligence Scale-Revised (range from 0-93 points), and the MMSE score (range from 0-30 points). Each of the component change scores is divided by the baseline sample standard deviation of that component, to form standardized z scores. These z scores are summed to form the composite. Z Scores could range from -5 to +5 with higher scores indicating less deficit and lower scores indicating greater deficit.	6 months
ADCS-PACC composite score	Combines tests that assess episodic memory, timed executive function and global cognition. Alzheimer's Disease Cooperative Study (ADCS) PACC (ADAS-PACC) is a composite score of: The Total Recall score from the Free and Cued Selective Reminding Test (FCSRT) (range from 0-48 points), The Delayed Recall score on the Logical Memory IIa subtest from the Wechsler Memory Scale (range from 0-25 points), the Digit Symbol Substitution Test score from the Wechsler Adult Intelligence Scale-Revised (range from 0-93 points), and the MMSE score (range from 0-30 points). Each of the component change scores is divided by the baseline sample standard deviation of that component, to form standardized z scores. These z scores are summed to form the composite. Z Scores could range from -5 to +5 with higher scores indicating less deficit and lower scores indicating greater deficit.	9 months
Olfactory Psychophysical Tasks scores	Using Sniffin' sticks, defines patient's olfactory threshold (T), discrimination (D) and identification (I). Scores: Male and Female threshold score (1-16); Male and Female discrimination score (4-16); Identification score (male: 3-16; female: 4-16); Threshold Discrimination Identification (TDI) composite score (male: 9-44; female: 11-43). Higher score indicates better olfactory performance.	Baseline
Olfactory Psychophysical Tasks scores	Using Sniffin' sticks, defines patient's olfactory threshold (T), discrimination (D) and identification (I). Scores: Male and Female threshold score (1-16); Male and Female discrimination score (4-16); Identification score (male: 3-16; female: 4-16); TDI composite score (male: 9-44; female: 11-43). Higher score indicates better olfactory performance.	6 months
Olfactory Psychophysical Tasks scores	Using Sniffin' sticks, defines patient's olfactory threshold (T), discrimination (D) and identification (I). Scores: Male and Female threshold score (1-16); Male and Female discrimination score (4-16); Identification score (male: 3-16; female: 4-16); TDI composite score (male: 9-44; female: 11-43). Higher score indicates better olfactory performance.	9 months
Changes in cortical thickness and grey matter volumes	Defines as MRI imaging changes of the hippocampus and entorhinal cortex	Baseline and 9 months
Changes in subfield segmentations of the hippocampus and entorhinal cortex	Using the Automatic Segmentation of Hippocampal subfields looking for changes in the hippocampus and entorhinal cortex	Baseline and 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the scores of Neuropsychological Test Battery (NTB)	Neuropsychological Test Battery (NTB) is a combination of widely used clinical neuropsychological tests measuring memory and executive function. he total Neuropsychological Test Battery (NTB) executive function is a composite score obtained from averaging the following three z-scores from the NTB: Wechsler Memory Scale Digit Span, Controlled Word Association Test (COWAT), and Category Fluency Test (CFT). The range in z scores is from -3 to 3; higher scores indicating less executive function deficit.	Baseline, 6 months and 9 months
Changes in the scores of Mini Mental State Examination (MMSE)	Mini Mental State Examination (MMSE) measures cognitive function and includes tests of orientation, attention, memory, language and visual-spatial skills. MMSE range 0 - 30; higher scores indicating less deficit.	Baseline, 6 months and 9 months
Changes in the scores of CDR scale (CDR)	Clinical Dementia Rating Scale (CDR) is a 5- point scale used to characterize six domains of cognitive and functional performance (Memory, Orientation, Judgment & Problem Solving, Community Affairs, Home & Hobbies, and Personal Care) applicable to Alzheimer's disease and related dementias. CDR Score is the sum of boxes scores range from 0 - 18; higher scores indicating worse deficit.	Baseline, 6 months and 9 months
Changes in the scores of Global Deterioration Scale(GDS)	GDS provides an overview of the stages of cognitive function for those suffering from primary degenerative dementia such as Alzheimer's disease. Geriatric Depression Scale (GDS) scores range from 0 - 30; higher scores indicating worse depression.	Baseline, 6 months and 9 months
Changes in the scores of Activities of Daily Living (ADCS-ADL)	ADCS-ADL is used for assessment of patient's ability to perform activities of daily living. ADCS-ADL is a 23-item activities of daily with score range from 0 - 78; lower scores indicating greater impairment.	Baseline, 6 months and 9 months
Changes in the scores of Quality of Life scale (QOL)	QOL measures satisfaction, perceptions of control, involvement, commitment and work-life balance, in terms of one's personal perception. QOL-AD score ranges from 13 - 52; higher scores indicating less deficit.	Baseline, 6 months and 9 months
Changes in odor discrimination scores	Odor discrimination score defines patient's ability to detect differences between odors.	Baseline, 9 months
Changes in the grey matter volumes of other structures of the primary olfactory cortex	Primary olfactory region images will use MPRAGE MRI sequence for grey matter volume	Baseline, 9 months
Changes in the cortical thickness of other structures of the primary olfactory cortex	Primary olfactory region images will use MPRAGE MRI sequence for cortical thickness	Baseline, 9 months

Collaborators and Investigators

• Sponsor: Evon Medics LLC
• Collaborators: Johns Hopkins University; National Institute on Aging (NIA); Howard University; Medical Home Development Group; Family and Medical Counseling Service, Inc
• Investigators: Principal Investigator: Evaristus Nwulia, MD, Evon Medics LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): April 30, 2023

Study Registration Dates

• First Submitted: September 28, 2021
• First Submitted That Met QC Criteria: November 4, 2021
• First Posted (Actual): November 17, 2021

Study Record Updates

• Last Update Posted (Actual): May 17, 2022
• Last Update Submitted That Met QC Criteria: May 12, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Memory; Cognition; Computerized Olfactory Training Device
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction; Physiological Effects of Drugs; Central Nervous System Stimulants
• Other Study ID Numbers: COTAG061981; 2R44AG061981-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No