δ in Dementia Clinical Trials (δND)

Novel Methods for Clinical Trials in Dementia and Cognitive Decline

The goal of this clinical trial is to demonstrate potential improvements in clinical trial methods relating to dementia and cognitive decline. The main questions it aims to answer are:

• Can an intervention's outcome be better assessed by a latent variable ("δ") integrating cognitive performance with functional status?
• Can latent biomarkers of δ guide the selection of an intervention that will modulate dementia severity?
• Can a latent variable, derived from information collected remotely from caregivers, preselect subjects most likely to respond to the intervention?
• Is the effect of the intervention in fact medicated by changes in the targeted biomarker?

In this case, the biomarker will be a latent variable derived from several proteins measured in blood (i.e., so-called "adipokines"). The intervention will be donepezil, a medication approved for the treatment of Alzheimer's Disease, but only recently associated with adipokine changes.

Participants with cognitive impairment and their caregivers will be interviewed by telephone and those newly prescribed donepezil by their provider for cognitive impairment will be recruited and enrolled. On the basis of the caregiver's report, the cognitively impaired subjects will be assigned to two groups based on a prediction of their response to donepezil. Researchers will compare those groups to see if dementia severity, as measured by δ, improves in predicted responders, and whether the change in the d-score is mediated by changes in adipokines.

Study Overview

• Status: Recruiting
• Conditions: Dementia; Alzheimer's Disease (AD); Cognitive Decline; Mild Cognitivie Impairment (MCI)
• Intervention / Treatment: Other: Donepezil

Detailed Description

Title: "Novel Methods for Clinical Trials in Dementia and Cognitive Decline"

Study Description: This is a double-blind assignment clinical study to test novel approaches to clinical trial methods. 1) The study team will pre-select cases most likely to benefit from adipokine modulation by a telephone assessment. 2) The study team will pre-select subjects with clinical and preclinical dementia most likely to respond to therapy. 3) The study team will test the drug donepezil's effect on dementia severity, in predicted responders and non-responders, as measured by a latent dementia phenotype "δ' and 4) test a latent Adipokines biomarker construct as a mediator of their association in the predicted responders.

Objectives:

Primary Objective: To assess donepezil's effect on dementia severity as measured by δ in LOI subgroups and across LOI subgroups.

Secondary Objective: To test Adipokines as a mediator of donepezil's effect on dTEL.

Tertiary/Exploratory: To test whether donepezil reverses dementia in cases preselected to by "LOI" analysis.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Samuel Guess; Phone Number: 210 567 8133; Email: guesss@uthscsa.edu
• Study Contact Backup: Name: Floyd Jones; Phone Number: 210 450 3158; Email: JONESFA@uthscsa.edu

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229-3900
      • Recruiting
      • Univeristy of Texas Health Science Center at San Antonio (UTHSCSA)
      • Contact: Samuel Guess; Phone Number: 210 567 8133; Email: guesss@uthscsa.edu
      • Contact: Floyd Jones; Phone Number: JONESFA@uthscsa.edu; Email: JONESFA@uthscsa.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 61 years to 96 years (Older Adult)
• Accepts Healthy Volunteers: No

Study Population

Community-dwelling male and female outpatients with cognitive impairment in Bexar County, Texas.

Description

Inclusion Criteria:

1. Ambulatory outpatient volunteers with co-informants.
2. Aged 65-100 years
3. Clinical diagnosis of AD, or MCI.
4. Capacity to give informed consent.
5. GDS score (15 item) ≤ 8.
6. No significant visual or hearing impairments
7. Standardized dECog score between 1.0 and 5.0 relative to ADNI's cohort.

Exclusion Criteria:

1. A history of psychosis, including visual hallucinations;
2. History or treatment for Parkinson's, or tremor, or Rapid Eye Movement (REM) behavior disorder;
3. History of bradycardia or syncopal events;
4. Treatment for cancer in the last 5 years (excluding skin cancers);
5. Major surgery in the last year;
6. Treatment for a seizure disorder with anticonvulsants;
7. Treatment for agitation or psychosis with neuroleptics (treatment of anxiety or insomnia allowed);
8. Current treatment with donepezil or any other AChEI or exposure within the last six months
9. With a recently started Donepezil Rx (< 2 weeks), inability to stop Donepezil treatment for 14 days prior to study enrollment.
10. AChEI treatment not appropriate due to negative risk/benefit ratio based on medical Hx and symptoms during screening. Evaluated by PI and referring clinician.
11. Co-participation in another study that the PI feels would pose a safety risk or adversely affect data integrity of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Predicted Responders; Group assignment determined by a response predictor algorithm derived from remotely acquired caregiver reports of cognitive performance. The donepezil administered during the study is prescribed by the subject provider as standard of care.	Other: Donepezil; Donepezil is administered as a standard of care treatment by the subject's provider.; Other Names: Aricept ®
Other: Predicted Non-Responders; Group assignment determined by a response predictor algorithm derived from remotely acquired caregiver reports of cognitive performance. The donepezil administered during the study is prescribed by the subject provider as standard of care.	Other: Donepezil; Donepezil is administered as a standard of care treatment by the subject's provider.; Other Names: Aricept ®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
dTEL change	Change in a latent dementia-specific phenotype derived from cognitive assessment.	At baseline, and weeks 4, 12 and 24.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ADIPOKINES change	Change in a latent construct derived from eight "Adipokine" proteins measured in blood.	Baseline and week 24.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dementia "Reversion"	The frequency of dementia "reversion" defined as a final dTEL score > -0.40, i.e., the optimal d-score that discriminates subjects with AD from those with MCI in the Alzheimer's Disease Neuroimaging Initiative (ADNI).	Week 24

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Donald R. Royall, MD, University of Texas

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2024
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2028

Study Registration Dates

• First Submitted: October 13, 2022
• First Submitted That Met QC Criteria: October 19, 2022
• First Posted (Actual): October 25, 2022

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: dementia; cognition; functional status; intelligence; adipokines
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease; Dementia; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Hydrocarbons, Cyclic; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Piperidines; Indans; Indenes; Donepezil
• Other Study ID Numbers: HSC20220551H; R01AG080548 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals. Data from this study may be requested from other researchers 5 years after the completion of the primary endpoint by contacting royall@uthscsa.edu
• IPD Sharing Time Frame: Data from this study may be requested from other researchers 5 years after the completion of the primary endpoint by contacting royall@uthscsa.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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