RQC for the Prevention of Alzheimer's Disease and Retinal Amyloid-β

Официальное название

A Randomized Phase II Study to Evaluate Oral RQC for the Prevention of Alzheimer's Disease and Retinal Amyloid-β

Обзор

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.

Вмешательства

• Препарат Resveratrol, Quercetin, and Curcumin (RQC)
  2000 mg Curcumin/day, taken twice daily for 24 months (galactomannan formulation, capsule form) 334 mg Resveratrol/day, taken twice daily for 24 months (galactomannan formulation, capsule form) 60 mg Quercetin/day, taken twice daily for 24 months (galactomannan formulation, capsule form)
• Препарат Curcumin
  2000 mg Curcumin/day, taken twice daily for 7 days preceding each study visit (baseline and months 3, 6, 12, 18, and 24 for a total of 42 non-consecutive days over 24 months.

Первичные конечные точки

• Change in Retinal Amyloid-β [Срок оценки: Baseline to 12 Months, Baseline to 24 Months]

Вторичные конечные точки (8)

• Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Score [Срок оценки: Baseline to 12 Months, Baseline to 24 Months]
• Change in Mini Mental State Examination (MMSE) Score [Срок оценки: Baseline to 12 Months, Baseline to 24 Months]
• Change in Superactivated Platelet (SAP) Percentage [Срок оценки: 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 [Срок оценки: Baseline to 12 Months, Baseline to 24 Months]
• Correlation Between Change in Retinal Amyloid-β and Change in Mini Mental State Examination (MMSE) Score [Срок оценки: Baseline to 12 Months, Baseline to 24 Months]
• Progression to Clinically Relevant Cognitive Decline (MMSE) [Срок оценки: Baseline to 12 Months, Baseline to 24 Months]
• Progression to Clinically Relevant Cognitive Decline (CDR-SB) [Срок оценки: Baseline to 12 Months, Baseline to 24 Months]
• Adverse Events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: Baseline, 12 Months, 24 Months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Профилактика

Центры проведения

США · 1 центр

• Zaparackas & Knepper Ltd. — Chicago

Публикации

• 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. PMID 28814675
• 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. PMID 20550967
• 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. PMID 33015311
• 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):e PMID 34430703
• 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. PMID 34366344
• 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. PMID 37459141
• 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. PMID 36449413

Идентификаторы

NCT: NCT06470061 · ZK-01-2024

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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