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

NCT06470061 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ZK-01-2024
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer Disease; Mild Cognitive Impairment; Cognitive Decline

Keywords

Alzheimer's disease; Mild cognitive impairment; Retinal amyloid-β; Microvascular biomarkers; Early Alzheimer's disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Score

  Baseline to 12 Months, Baseline to 24 Months

• Change in Mini Mental State Examination (MMSE) Score

  Baseline to 12 Months, Baseline to 24 Months

• Change in Superactivated Platelet (SAP) Percentage

  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

  Baseline to 12 Months, Baseline to 24 Months

• Correlation Between Change in Retinal Amyloid-β and Change in Mini Mental State Examination (MMSE) Score

  Baseline to 12 Months, Baseline to 24 Months

Study Arms (2)

Resveratrol, Quercetin, and Curcumin (RQC)

EXPERIMENTAL

Resveratrol, Quercetin, and Curcumin (RQC) galactomannan formulations taken orally twice daily for 24 months.

Drug: Resveratrol, Quercetin, and Curcumin (RQC)

Curcumin

PLACEBO COMPARATOR

Curcumin taken orally twice daily during the 7 days preceding each study visit in order to label retinal amyloid-β.

Drug: Curcumin

Interventions

Resveratrol, Quercetin, and Curcumin (RQC) DRUG

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)

Also known as: Resveratrol, Quercetin, and Curcumin

Resveratrol, Quercetin, and Curcumin (RQC)

Curcumin DRUG

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.

Curcumin

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Zaparackas and Knepper LTD: lead
• Northwestern University Feinberg School of Medicine: collaborator

Study Sites (1)

Zaparackas & Knepper Ltd.

Chicago, Illinois, 60611, United States

Location

Related Publications (7)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 34430703 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 37459141 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

Resveratrol; Quercetin; Curcumin

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Stilbestrols; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polyphenols; Phenols; Flavonols; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Diarylheptanoids; Heptanes; Alkanes; Hydrocarbons, Acyclic; Catechols

Study Officials

• Paul A Knepper, MD, PhD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanie Aman

CONTACT

312-337-1285; knezap@sbcglobal.net

Nicholas M Pfahler

CONTACT

773-677-0447; maxpfahler@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2024
• First Posted: June 24, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: June 26, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF, CSR
• Time Frame: After completion of the study for a period of at least 2 years.
• Access Criteria: Qualified external researchers. Approved by PI.

Locations

US (1)