δND: δ in Dementia Clinical Trials

Sponsor

The University of Texas Health Science Center at San Antonio (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05592678

Collaborator

National Institute on Aging (NIA) (NIH)

200

Enrollment

Location

Arms

Anticipated Duration (Months)

3.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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?
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 with cognitive impairment will be treated for six-months with donepezil. 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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease (AD) Dementia Cognitive Decline Mild Cognitivie Impairment (MCI)	Drug: Donepezil	Phase 2/Phase 3

Detailed Description

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

Study Description: This is a double-blind assignment open label clinical trial 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 test novel clinical trial methods relevant to dementia.

Secondary Objectives:

To test donepezil's effect on dementia severity as measured by δ.
To test Adipokines as a mediator of donepezil's effect on δ.

Endpoints: Primary Endpoint: Dementia severity as measured by the latent phenotype "δ" using the "dTEL" homolog.

Secondary Endpoint: Change in Adipokines as a mediator of donepezil's effect on dTEL.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

a double-blind assignment open label clinical triala double-blind assignment open label clinical trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Blind to group assignment

Primary Purpose:

Treatment

Official Title:

Novel Methods for Clinical Trials in Dementia and Cognitive Decline

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Feb 1, 2027

Anticipated Study Completion Date :

Nov 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Predicted Responders Group assignment determined by a response predictor algorithm derived from remotely acquired caregiver reports of cognitive performance.	Drug: Donepezil 6 months of open label treatment at 10mg PO QD (maximum) Other Names: Aricept ®
Active Comparator: Predicted Non-Responders Group assignment determined by a response predictor algorithm derived from remotely acquired caregiver reports of cognitive performance.	Drug: Donepezil 6 months of open label treatment at 10mg PO QD (maximum) Other Names: Aricept ®

Arm

Intervention/Treatment

Active Comparator: Predicted Responders

Group assignment determined by a response predictor algorithm derived from remotely acquired caregiver reports of cognitive performance.

Drug: Donepezil

6 months of open label treatment at 10mg PO QD (maximum)

Other Names:

Aricept ®

Active Comparator: Predicted Non-Responders

Group assignment determined by a response predictor algorithm derived from remotely acquired caregiver reports of cognitive performance.

Drug: Donepezil

6 months of open label treatment at 10mg PO QD (maximum)

Other Names:

Aricept ®

Outcome Measures

Primary Outcome Measures

dTEL change [At baseline, and weeks 4, 12 and 24.]
Change in a latent dementia-specific phenotype derived from cognitive assessment.

Secondary Outcome Measures

ADIPOKINES change [Baseline and week 24.]
Change in a latent construct derived from eight "Adipokine" proteins measured in blood.

Other Outcome Measures

Dementia "Reversion" [Week 24]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ambulatory outpatient volunteers with competent informants
Aged 65-100 years
Clinical diagnosis of AD, or MCI
Capacity to give informed consent
Geriatric Depression Scale (GDS) (15 item) score ≤ 6
No significant visual or hearing impairments
A standardized dECog score between 0.0 and -1.0 relative to ADNI's cohort

Exclusion Criteria:

A self-reported diagnosis of "Major Depression" (treatment with "antidepressants" not exclusionary)
A history of psychosis, including visual hallucinations
History or treatment for Parkinson's, or tremor, or Rapid Eye Movement (REM) behavior disorder
History or treatment for atrial fibrillation
Treatment for cancer in the last 5 years (excluding skin cancers)
Major surgery in the last year
Current treatment with acetylcholinesterase inhibitor (AChEI) (memantine is acceptable). -Potential subjects on an AChEI can washout for three months and be rescreened.
Current treatment with anti-convulsants, mood stabilizers, neuroleptics, opiates, muscle relaxants, or systemic steroids