Alzheimer's Disease (AD)δNDNCT05592678
δ in Dementia Clinical Trials
A study testing Donepezil in people with Alzheimer's Disease (AD) and Dementia, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial summary
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?… Read more about this study
- Who is it for?
- Ages 65 to 100 years
- Conditions the study is for
- Alzheimer's Disease (AD), Dementia, Cognitive Decline
- What is being tested?
- Donepezil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Aug 2024to 30 Nov 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 100 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Ambulatory outpatient volunteers with co-informants.
- Aged 65-100 years
- Clinical diagnosis of AD, or MCI.
- Capacity to give informed consent.
- GDS score (15 item) ≤ 8.
- No significant visual or hearing impairments
- Standardized dECog score between 1.0 and 5.0 relative to ADNI's cohort.
Who cannot join
- A history of psychosis, including visual hallucinations;
- History or treatment for Parkinson's, or tremor, or Rapid Eye Movement (REM) behavior disorder;
- History of bradycardia or syncopal events;
- Treatment for cancer in the last 5 years (excluding skin cancers);
- Major surgery in the last year;
- Treatment for a seizure disorder with anticonvulsants;
Show all 11Show fewer
- Treatment for agitation or psychosis with neuroleptics (treatment of anxiety or insomnia allowed);
- Current treatment with donepezil or any other AChEI or exposure within the last six months
- With a recently started Donepezil Rx (< 2 weeks), inability to stop Donepezil treatment for 14 days prior to study enrollment.
- AChEI treatment not appropriate due to negative risk/benefit ratio based on medical Hx and symptoms during screening. Evaluated by PI and referring clinician.
- Co-participation in another study that the PI feels would pose a safety risk or adversely affect data integrity of this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Univeristy of Texas Health Science Center at San Antonio (UTHSCSA)
San Antonio, Texas, 78229-3900
Samuel Guess, 210 567 8133, guesss@uthscsa.edu
Floyd Jones, JONESFA@uthscsa.edu, JONESFA@uthscsa.edu
About this study
Official title: 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?
Read more
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.
Read the 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.
- Being tested
- Donepezil
- Keywords
- adipokines, cognition, dementia, functional status, intelligence
- Medical subject headings
- Alzheimer Disease, Dementia, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DonepezilOther
Also called Aricept ®
Donepezil is administered as a standard of care treatment by the subject's provider.
| Study group | Role | What they receive |
|---|---|---|
| Predicted Responders | Other | 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. Receives: Other: Donepezil |
| Predicted Non-Responders | Other | 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. Receives: Other: Donepezil |
What is being measured
The primary outcome is the main question the study is designed to answer.
dTEL change
Change in a latent dementia-specific phenotype derived from cognitive assessment.
Measured: At baseline, and weeks 4, 12 and 24.
Secondary outcomes (1)
ADIPOKINES change
Change in a latent construct derived from eight "Adipokine" proteins measured in blood.
Measured: Baseline and week 24.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2022
- Study start5 Aug 2024
- Primary completion30 Nov 2028 (estimated)
- Study completion30 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer's Disease (AD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- a double-blind group assignment open label study, one group has suspected Adipokine-related dementia and the other group does not.
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Texas Health Science Center at San Antonio
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Donald Royall, The University of Texas Health Science Center at San Antonio
- Investigators
- Donald R. Royall, MD, Principal investigator, University of Texas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05592678
- Sponsor's protocol ID
- HSC20220551H
- Other IDs
- R01AG080548
- Acronym
- δND
- Status last verified
- Apr 2026
- First submitted
- 13 Oct 2022
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Methods for Clinical Trials in Dementia and Cognitive Decline
- ClinicalTrials.gov ID
- NCT05592678
- Acronym / sponsor ID
- δND / HSC20220551H
- Keywords
- adipokines, cognition, dementia, functional status, intelligence
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 5 Aug 2024 (actual)
- Primary completion
- 30 Nov 2028 (estimated)
- Study completion
- 30 Nov 2028 (estimated)
- First posted
- 25 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- a double-blind group assignment open label study, one group has suspected Adipokine-related dementia and the other group does not.
| Arm | Type | Receives |
|---|---|---|
| Predicted Responders | Other | Other: DonepezilGroup 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. |
| Predicted Non-Responders | Other | Other: DonepezilGroup 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. |
Who may qualify
- Ages
- 65 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (7 listed)
- Ambulatory outpatient volunteers with co-informants.
- Aged 65-100 years
- Clinical diagnosis of AD, or MCI.
- Capacity to give informed consent.
- GDS score (15 item) ≤ 8.
Key exclusion criteria (11 listed)
- A history of psychosis, including visual hallucinations;
- History or treatment for Parkinson's, or tremor, or Rapid Eye Movement (REM) behavior disorder;
- History of bradycardia or syncopal events;
- Treatment for cancer in the last 5 years (excluding skin cancers);
- Major surgery in the last year;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DonepezilAlso: Aricept ®Donepezil is administered as a standard of care treatment by the subject's provider. | Other | Predicted Non-Responders, Predicted Responders |
Primary outcome
dTEL change
Time frame: At baseline, and weeks 4, 12 and 24.
Change in a latent dementia-specific phenotype derived from cognitive assessment.
1 secondary outcome
ADIPOKINES change
Time frame: Baseline and week 24.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Donald R. Royall, MD principal investigator
University of Texas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Donepezil in people with Alzheimer's Disease (AD) and Dementia, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Samuel Guess (210 567 8133, guesss@uthscsa.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
dTEL change (time frame: At baseline, and weeks 4, 12 and 24.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2026.