δ in Dementia Clinical Trials

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Novel Methods for Clinical Trials in Dementia and Cognitive Decline

Conditions
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Alzheimer's Disease (AD), Dementia, Cognitive Decline, Mild Cognitivie Impairment (MCI)

Intervention / Treatment
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* Drug: Donepezil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: a double-blind assignment open label clinical trial
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adipokines, cognition, dementia, functional status, intelligence