Clinical trial NCT05172128: Effect of Blueberry Supplementation on Alzheimer's Biomarkers
Official title: Effect of Blueberry Supplementation on Alzheimer's Biomarkers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mild Cognitive Impairment
Alzheimer Disease
Keywords: MCI
biomarkers
memory loss
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: U.S. Highbush Blueberry Council
First posted: 2021-12-29
Enrollment: 12
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to study the effects of blueberries on neuronal, glial, and pathology blood biomarkers in Mild Cognitive Impairment (MCI) and to estimate sample size for future confirmatory studies. The blood biomarkers to be measured are Neurofilament light (NfL), glial fibrillary acidic protein (GFAP), Aß40, Aß42, p-tau181, and cytokines, using an ultra-sensitive state-of-the-art immunoassay.

Detailed description: After determining subject eligibility and after subjects have abstained from consuming all berry fruits (including red wine) for 2 weeks, subjects will have blood drawn for biomarkers and will then will undergo 12 weeks of blueberry supplementation in the form of 18 grams lyophilized blueberry powder mixed with water and taken twice daily with meals. All subjects will be asked to abstain from berry fruits (including red wine) for the duration of the 12 week trial. Subjects will receive telephone calls at 4 and 8 weeks to check compliance as well as concomitant medications and adverse events and then all subjects will return at 12 weeks for a repeat biomarker blood draw. Plasma NfL, GFAP, Aβ40, Aβ42, p-tau181, and cytokine biomarker assays will be done using the Quanterix SR-X instrument, a new, state-of-the-art digital immunoassay platform employing Simoa technology, which enables the detection and quantification of biomarkers previously difficult or impossible to measure.

Eligibility criteria: Inclusion Criteria:

1. 55 to 85 years old inclusive
2. Meets criteria for amnestic Mild Cognitive Impairment defined by education adjusted performance on the Wechsler Memory Scale (WMS) III Logical Memory delayed recall score and clinical evaluation.
3. Medically stable

Exclusion Criteria:

1. Dementia
2. Significant confounding active neurological/psychiatric disease
3. Participation in an experimental investigational drug trial in the past 30 days
4. Unwilling to restrict consumption of anthocyanin-rich foods
5. Inability to complete cognitive testing (e.g. significant visual or hearing impairment)
6. Allergy or intolerance to blueberries
7. Significant gastrointestinal disorders or surgery that influences digestion and absorption
8. Presence of unstable, acutely symptomatic, or life-limiting illness
9. Women of childbearing potential

Primary outcomes:
measure: Change in Blood Neurofilament Light (NfL) Levels as Measured by Blood Biomarker Assay
timeFrame: Baseline, 12 weeks
measure: Change in Blood Glial Fibrillary Acidic Protein (GFAP) Levels as Measured by Blood Biomarker Assay
timeFrame: Baseline, 12 weeks
measure: Change in Blood Amyloid Beta 42/40 as Measured by Blood Biomarker Assay
timeFrame: Baseline, 12 weeks
measure: Change in P-tau 181 as Measured by Blood Biomarker Assay
timeFrame: Baseline, 12 weeks
measure: Change in Blood Interleukin-6 (IL-6) Levels as Measured by Blood Biomarker Assay
timeFrame: Baseline, 12 weeks
measure: Change in Tumor Necrosis Factor (TNF-alpha) Levels as Measured by Blood Biomarker Assay
timeFrame: Baseline, 12 weeks
measure: Change in Brain-derived Neurotrophic Factor (BDNF)
timeFrame: Baseline, 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Murali Doraiswamy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Miller MG, Hamilton DA, Joseph JA, Shukitt-Hale B. Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial. Eur J Nutr. 2018 Apr;57(3):1169-1180. doi: 10.1007/s00394-017-1400-8. Epub 2017 Mar 10.
citation: Wang S, Cui Y, Wang C, Xie W, Ma L, Zhu J, Zhang Y, Dang R, Wang D, Wu Y, Wu Q. Protective Effects of Dietary Supplementation with a Combination of Nutrients in a Transgenic Mouse Model of Alzheimer's Disease. PLoS One. 2015 Nov 25;10(11):e0143135. doi: 10.1371/journal.pone.0143135. eCollection 2015.
citation: Jeong HR, Jo YN, Jeong JH, Kim HJ, Kim MJ, Heo HJ. Blueberry (Vaccinium virgatum) leaf extracts protect against Abeta-induced cytotoxicity and cognitive impairment. J Med Food. 2013 Nov;16(11):968-76. doi: 10.1089/jmf.2013.2881. Epub 2013 Oct 11.
citation: Brewer GJ, Torricelli JR, Lindsey AL, Kunz EZ, Neuman A, Fisher DR, Joseph JA. Age-related toxicity of amyloid-beta associated with increased pERK and pCREB in primary hippocampal neurons: reversal by blueberry extract. J Nutr Biochem. 2010 Oct;21(10):991-8. doi: 10.1016/j.jnutbio.2009.08.005. Epub 2009 Dec 1.
citation: Ou Y, Hu H, Wang Z, Xu W, Tan L, et al. Plasma neurofilament light as a longitudinal biomarker of neurodegeneration in Alzheimer's disease. Brain Science Advances. 2019;5(2):94-105.