RQC for the Prevention of Alzheimer's Disease and Retinal Amyloid-β
NCT Number: NCT06470061
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Alzheimer Disease|Mild Cognitive Impairment|Cognitive Decline
Interventions: DRUG: Resveratrol, Quercetin, and Curcumin (RQC)|DRUG: Curcumin
Sponsor: Zaparackas and Knepper LTD
Collaborators: Northwestern University Feinberg School of Medicine
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 200
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: DOUBLE (INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: PREVENTION
Start Date: 2024-07
Completion Date: 2027-07
Locations: Zaparackas & Knepper Ltd., Chicago, Illinois, 60611, United States

Summary:
The goal of this clinical trial is to evaluate whether oral resveratrol, quercetin, and curcumin (RQC) can prevent the accumulation of retinal amyloid-β and/or cognitive decline over 24 months in adults aged 50-90 with Stage 1 or 2 Alzheimer's disease as described in FDA-2013-D-0077. The trial will also evaluate the safety and tolerability of RQC. Curcumin, which binds to amyloid-β, will act as a fluorescent label to identify retinal amyloid-β in vivo using optical coherence tomography (OCT)-autofluorescence imaging. The investigators will longitudinally evaluate the effect of RQC on retinal amyloid-β load cognitive outcomes including the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) and the Mini Mental State Examination (MMSE), and potential microvascular biomarkers. The investigators will also evaluate associations between retinal amyloid-β and progression to early Alzheimer's disease (mild cognitive impairment). The investigators will compare RQC, taken daily for 24 months, with curcumin alone, taken only during the 7 days preceding each of the six study visits to see if RQC can prevent (or reduce) amyloid-β and prevent the onset of mild cognitive impairment.

Primary Outcome Measures: Change in Retinal Amyloid-β, Retinal amyloid-β is identified using optical coherence tomography (OCT)-autofluorescence imaging and measured using a composite score called the retinal amyloid index (RAI), a continuous variable incorporating number, total area, and total fluorescence intensity of retinal Aβ spots. The change in RAI scores will be compared between RQC and control groups using linear mixed-effects models for repeated measures., Baseline to 12 Months, Baseline to 24 Months
Secondary Outcome Measures: Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Score, The Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) is used to differentiate stages of cognitive impairment. It assesses six cognitive and functional domains including memory, orientation, judgement, community affairs, home hobbies, and personal care. Each of the six CDR domains is scored 0 to 3, with the Sum of Boxes (SB) being the sum of the six domains on a 0-18 numerical scale. The CDR-SB is scored by trained physicians after interviewing both participants and their informants. Change in CDR-SB scores will be compared between RQC and control groups using linear mixed-effects models for repeated measures., Baseline to 12 Months, Baseline to 24 Months|Change in Mini Mental State Examination (MMSE) Score, The Mini Mental State Examination (MMSE) is an instrument used to screen for cognitive impairment. The test consists of 11-questions that evaluate five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. The MMSE is scored on a numerical 0-30 scale by trained physicians after interviewing participants. Change in MMSE scores will be compared between RQC and control groups using linear mixed-effects models for repeated measures., Baseline to 12 Months, Baseline to 24 Months|Change in Superactivated Platelet (SAP) Percentage, Superactivated platelets (SAPs) are a procoagulant sub-type of activated platelet that are increased in mild cognitive impairment (MCI) and Alzheimer's disease and are associated with disease progression \[Pfahler, 2018; Prodan, 2011\]. SAPs are prepared from whole blood samples and induced in vitro by dual platelet agonists thrombin and convulxin (collagen substitute). SAPs are identified by inactivated integrin αIIbβ3 and high levels of surface fibrinogen binding and measured using flow cytometry as the percentage of total platelets positive for SAP markers. Change in the percentage of SAPs will be compared between RQC and control groups using linear mixed-effects models for repeated measures., Baseline to 12 Months, Baseline to 24 Months|Correlation Between Change in Retinal Amyloid-β and Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Score, The Pearson correlation coefficient (r) between change in retinal amyloid-β as measured using the retinal amyloid index (RAI) score and change in CDR-SB scores as measured using the 0-18 numerical scale equating to the sum of the six CDR domains, each of which is scored 0 to 3. The retinal amyloid-β RAI score is a continuous variable that incorporates number, total area, and total fluorescence intensity of retinal Aβ spots. For example, a subject may have a RAI score of 20.4 and a CDR-SB score of 1., Baseline to 12 Months, Baseline to 24 Months|Correlation Between Change in Retinal Amyloid-β and Change in Mini Mental State Examination (MMSE) Score, The Pearson correlation coefficient (r) between change in retinal amyloid-β as measured using the retinal amyloid index (RAI) score and change in MMSE scores as measured using the 0-30 numerical MMSE scale. The retinal amyloid-β RAI score is a continuous variable that incorporates number, total area, and total fluorescence intensity of retinal Aβ spots. For example, a subject may have a RAI score of 20.4 and a MMSE score of 26., Baseline to 12 Months, Baseline to 24 Months|Progression to Clinically Relevant Cognitive Decline (MMSE), The effect of RQC on clinically significant cognitive decline (defined as a decrease of 4 or more points from baseline on MMSE) will be evaluated using Cox proportional hazards models., Baseline to 12 Months, Baseline to 24 Months|Progression to Clinically Relevant Cognitive Decline (CDR-SB), The effect of RQC on clinically significant cognitive decline (defined as an increase of 0.5 or more points from baseline on CDR-SB) will be evaluated using Cox proportional hazards models., Baseline to 12 Months, Baseline to 24 Months|Adverse Events (AEs) and Serious Adverse Events (SAEs), Adverse events (AEs) and serious adverse events (SAEs) will be identified and graded according to the CTCAE v5.0 after interviewing participants and reviewing study records., Baseline, 12 Months, 24 Months