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

NCT05122598 | Unknown Phase 2 DMC FDA Drug

• 2 other identifiers: COTAG0619812R44AG061981-03
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

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

Keywords

Cognition; Memory; Alzheimer's Disease; Computerized Olfactory Training Device

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (9)

• Changes in the scores of Neuropsychological Test Battery (NTB)

  Baseline, 6 months and 9 months

• Changes in the scores of Mini Mental State Examination (MMSE)

  Baseline, 6 months and 9 months

• Changes in the scores of CDR scale (CDR)

  Baseline, 6 months and 9 months

• Changes in the scores of Global Deterioration Scale(GDS)

  Baseline, 6 months and 9 months

• Changes in the scores of Activities of Daily Living (ADCS-ADL)

  Baseline, 6 months and 9 months

Study Arms (2)

Computerized Olfactory Training (COT) Device with olfactory stimulants

ACTIVE COMPARATOR

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

Sham/COT Device

SHAM COMPARATOR

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

Interventions

COT DRUG

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.

Also known as: COT with olfactory stimulants

Computerized Olfactory Training (COT) Device with olfactory stimulants

Sham DRUG

Sham COT uses artificially scented compressed room air instead of olfactory stimulants and has control cognitive olfactory tasks.

Also known as: Sham COT

Sham/COT Device

Eligibility Criteria

• Age: 55 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 55-95 years; female must be post-menopausal for ≥ 2 consecutive years
• Probable mild AD according to the core clinical criteria outlined in the National Institute on Aging/Alzheimer's Association (NIA-AA) Guidelines
• 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
• 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
• Screening MRI without evidence of infection, infarction, or other focal lesions of neurological disease; and no significant nasal disease.
• All participants must have a study partner with normal cognitive function.

You may not qualify if:

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

Sponsors & Collaborators

• Evon Medics LLC: lead
• Howard University: collaborator
• Family and Medical Counseling Service, Inc: collaborator
• Medical Home Development Group: collaborator
• National Institute on Aging (NIA): collaborator
• Johns Hopkins University: collaborator

Study Sites (3)

Clinics of Dr. Edwin Chapman @ MHDG

Washington D.C., District of Columbia, 20002, United States

RECRUITING

Family and Medical Counseling Service, Inc

Washington D.C., District of Columbia, 20020, United States

RECRUITING

Howard University (HU)

Washington D.C., District of Columbia, 20060, United States

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease; Memory Disorders

Interventions

salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Evaristus Nwulia, MD

  Evon Medics LLC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Evaristus Nwulia, MD

CONTACT

410-227-2005; enwulia@evonmedics.org

Maria Hipolito, MD

CONTACT

571-241-2766; mhipolito@evonmedics.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2021
• First Posted: November 17, 2021
• Study Start: November 15, 2021
• Primary Completion: April 1, 2023
• Study Completion: April 30, 2023
• Last Updated: May 17, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)