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

June 24, 2024 updated by: Zaparackas and Knepper LTD

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Resveratrol, Quercetin, and Curcumin (RQC)
Resveratrol, Quercetin, and Curcumin (RQC) galactomannan formulations taken orally twice daily for 24 months.
Drug: 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)

Other Names:
  • Resveratrol, Quercetin, and Curcumin
Placebo Comparator: Curcumin
Curcumin taken orally twice daily during the 7 days preceding each study visit in order to label retinal amyloid-β.
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Retinal Amyloid-β
Time Frame: Baseline to 12 Months, Baseline to 24 Months
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

Outcome Measure
Measure Description
Time Frame
Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Score
Time Frame: Baseline to 12 Months, Baseline to 24 Months
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
Time Frame: Baseline to 12 Months, Baseline to 24 Months
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
Time Frame: Baseline to 12 Months, Baseline to 24 Months
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
Time Frame: Baseline to 12 Months, Baseline to 24 Months
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
Time Frame: Baseline to 12 Months, Baseline to 24 Months
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)
Time Frame: Baseline to 12 Months, Baseline to 24 Months
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)
Time Frame: Baseline to 12 Months, Baseline to 24 Months
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)
Time Frame: Baseline, 12 Months, 24 Months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zaparackas and Knepper LTD

Collaborators

Northwestern University Feinberg School of Medicine

Investigators

  • Principal Investigator: Paul A Knepper, MD, PhD, Northwestern University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2024

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

July 1, 2027

Study Registration Dates

First Submitted

May 22, 2024

First Submitted That Met QC Criteria

June 19, 2024

First Posted (Actual)

June 24, 2024

Study Record Updates

Last Update Posted (Actual)

June 26, 2024

Last Update Submitted That Met QC Criteria

June 24, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZK-01-2024

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All IPD that underlie results in a publication will be shared with qualified external researchers upon request and PI approval. All data provided is anonymized to respect the privacy of participants in the trial according to applicable laws and regulations.

IPD Sharing Time Frame

After completion of the study for a period of at least 2 years.

IPD Sharing Access Criteria

Qualified external researchers. Approved by PI.

IPD Sharing Supporting Information Type

  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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