Clinical trial NCT06470061: RQC for the Prevention of Alzheimer's Disease and Retinal Amyloid-β
Official title: A Randomized Phase II Study to Evaluate Oral RQC for the Prevention of Alzheimer's Disease and Retinal Amyloid-β
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Alzheimer Disease
Mild Cognitive Impairment
Cognitive Decline
Keywords: Alzheimer's disease
Mild cognitive impairment
Retinal amyloid-β
Microvascular biomarkers
Early Alzheimer's disease
Lead sponsor: Zaparackas and Knepper LTD
Sponsor class: OTHER
Collaborators: name: Northwestern University Feinberg School of Medicine
First posted: 2024-06-24
Enrollment: 200
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: Inclusion Criteria:

* 50-90 years of age at screening.
* Male or female
* Any race or ethnicity.
* Provide written informed consent.
* Availability for the duration of the study.
* Ability to speak, read, and understand English.
* Ability to take oral medication and be willing to adhere to the RQC regimen.
* Have adequate literacy, vision, and hearing for neuropsychological testing at screening

Exclusion Criteria:

* MMSE score 0-25, indicating more than subtle cognitive abnormalities
* CDR-SB score \> 0, indicating functional impairment
* Clinical diagnosis of any non-Alzheimer's disease (AD) type of mild cognitive impairment (MCI) or dementia
* Taking pharmaceutical anti-Aβ monoclonal antibodies (i.e., Leqembi, Aduhelm).
* Participation in another clinical study with an investigational product during the last 90 days.
* Presence of hepatic disease or kidney disease
* Clinically significant or unstable hematologic, cardiovascular, pulmonary, gastrointestinal, endocrine metabolic, or other systemic disease.
* Diagnosis of gastrointestinal or stomach condition including but not limited to irritable bowel syndrome (IBS), ulcerative colitis, peptic ulcers, Crohn's disease, gastroesophageal reflux disease, gastritis, severe dyspepsia, and intestinal malabsorption.
* Clinically significant abnormal values in hematology, coagulation and platelet function, clinical chemistry, or urinalysis at screening (such as those with prolonged prothrombin time (PT), anemia, low neutrophil or platelet count, elevated liver function tests, low glomerular filtration rate).

Primary outcomes:
measure: Change in Retinal Amyloid-β
timeFrame: Baseline to 12 Months, Baseline to 24 Months
Secondary outcomes:
measure: Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Score
timeFrame: Baseline to 12 Months, Baseline to 24 Months
measure: Change in Mini Mental State Examination (MMSE) Score
timeFrame: Baseline to 12 Months, Baseline to 24 Months
measure: Change in Superactivated Platelet (SAP) Percentage
timeFrame: Baseline to 12 Months, Baseline to 24 Months
measure: Correlation Between Change in Retinal Amyloid-β and Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Score
timeFrame: Baseline to 12 Months, Baseline to 24 Months
measure: Correlation Between Change in Retinal Amyloid-β and Change in Mini Mental State Examination (MMSE) Score
timeFrame: Baseline to 12 Months, Baseline to 24 Months
measure: Progression to Clinically Relevant Cognitive Decline (MMSE)
timeFrame: Baseline to 12 Months, Baseline to 24 Months
measure: Progression to Clinically Relevant Cognitive Decline (CDR-SB)
timeFrame: Baseline to 12 Months, Baseline to 24 Months
measure: Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline, 12 Months, 24 Months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Zaparackas & Knepper Ltd.
state: Illinois
Study officials:
affiliation: Northwestern University
name: Paul A Knepper, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koronyo Y, Biggs D, Barron E, Boyer DS, Pearlman JA, Au WJ, Kile SJ, Blanco A, Fuchs DT, Ashfaq A, Frautschy S, Cole GM, Miller CA, Hinton DR, Verdooner SR, Black KL, Koronyo-Hamaoui M. Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer's disease. JCI Insight. 2017 Aug 17;2(16):e93621. doi: 10.1172/jci.insight.93621. eCollection 2017 Aug 17.
citation: Koronyo-Hamaoui M, Koronyo Y, Ljubimov AV, Miller CA, Ko MK, Black KL, Schwartz M, Farkas DL. Identification of amyloid plaques in retinas from Alzheimer's patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. Neuroimage. 2011 Jan;54 Suppl 1:S204-17. doi: 10.1016/j.neuroimage.2010.06.020. Epub 2010 Jun 13.
citation: Dumitrascu OM, Lyden PD, Torbati T, Sheyn J, Sherzai A, Sherzai D, Sherman DS, Rosenberry R, Cheng S, Johnson KO, Czeszynski AD, Verdooner S, Frautschy S, Black KL, Koronyo Y, Koronyo-Hamaoui M. Sectoral segmentation of retinal amyloid imaging in subjects with cognitive decline. Alzheimers Dement (Amst). 2020 Sep 28;12(1):e12109. doi: 10.1002/dad2.12109. eCollection 2020.
citation: Ngolab J, Donohue M, Belsha A, Salazar J, Cohen P, Jaiswal S, Tan V, Gessert D, Korouri S, Aggarwal NT, Alber J, Johnson K, Jicha G, van Dyck C, Lah J, Salloway S, Sperling RA, Aisen PS, Rafii MS, Rissman RA. Feasibility study for detection of retinal amyloid in clinical trials: The Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial. Alzheimers Dement (Amst). 2021 Aug 17;13(1):e12199. doi: 10.1002/dad2.12199. eCollection 2021.
citation: Tadokoro K, Yamashita T, Kimura S, Nomura E, Ohta Y, Omote Y, Takemoto M, Hishikawa N, Morihara R, Morizane Y, Abe K. Retinal Amyloid Imaging for Screening Alzheimer's Disease. J Alzheimers Dis. 2021;83(2):927-934. doi: 10.3233/JAD-210327.
citation: Sims JR, Zimmer JA, Evans CD, Lu M, Ardayfio P, Sparks J, Wessels AM, Shcherbinin S, Wang H, Monkul Nery ES, Collins EC, Solomon P, Salloway S, Apostolova LG, Hansson O, Ritchie C, Brooks DA, Mintun M, Skovronsky DM; TRAILBLAZER-ALZ 2 Investigators. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. 2023 Aug 8;330(6):512-527. doi: 10.1001/jama.2023.13239.
citation: van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, Sabbagh M, Vellas B, Watson D, Dhadda S, Irizarry M, Kramer LD, Iwatsubo T. Lecanemab in Early Alzheimer's Disease. N Engl J Med. 2023 Jan 5;388(1):9-21. doi: 10.1056/NEJMoa2212948. Epub 2022 Nov 29.