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Blood biomarkers as surrogate endpoints of treatment responses to aerobic exercise and cognitive training (ACT) in amnestic mild cognitive impairment: the blood biomarkers study protocol of a randomized controlled trial (the ACT Trial).
Trials. 2020 Jan 06; 21(1):19.T

Abstract

BACKGROUND

Alzheimer's disease (AD) is an epidemic with tremendous public health impacts because there are currently no disease-modifying therapeutics. Randomized controlled trials (RCTs) for prevention of AD dementia often use clinical endpoints that take years to manifest (e.g., cognition) or surrogate endpoints that are costly or invasive (e.g., magnetic resonance imaging [MRI]). Blood biomarkers represent a clinically applicable alternative surrogate endpoint for RCTs that would be both cost-effective and minimally invasive, but little is known about their value as surrogate endpoints for treatment responses in the prevention of AD dementia.

METHODS

The objective of this study is to investigate blood neuropathological, neurodegenerative, and neurotrophic biomarkers as surrogate endpoints for treatment responses to three interventions in older adults with amnestic mild cognitive impairment (aMCI, a prodromal stage of AD): aerobic exercise, cognitive training, and combined aerobic exercise and cognitive training (ACT). We chose these three sets of biomarkers for their unique mechanistic associations with AD pathology, neurodegeneration and neurogenesis. This study is built on the ACT Trial (1R01AG055469), a single-blinded, multi-site, 2 × 2 factorial phase II RCT that examines the synergistic effects of a 6-month ACT intervention on cognition and MRI biomarkers (AD-signature cortical thickness and hippocampal volume) (n = 128). In this ACT Trial blood biomarkers study, we will enroll 120 ACT Trial participants with aMCI and measure blood biomarkers at baseline and at 3, 6, 12, and 18 months. The goals are to (1) determine the effect of interventions on blood biomarkers over 6 months, (2) evaluate blood biomarkers as surrogate endpoints for predicting cognitive responses to interventions over 18 months, and (3, exploratory) examine blood biomarkers as surrogate endpoints for predicting brain MRI biomarker responses to interventions over 18 months.

DISCUSSION

This study aims to identify new blood biomarkers that can track cognitive decline or AD-related brain atrophy among patients with aMCI subjected to a regimen of aerobic exercise and cognitive training. Findings from this study will drive the further use of blood biomarkers in developing effective prevention and treatment strategies for AD dementia.

TRIAL REGISTRATION

ClinicalTrials.gov, NCT03313895. Registered on 18 October 2017.

Authors+Show Affiliations

Department of Lab Medicine and Pathology, University of Minnesota, 420 Delaware Street SE, MMC 609, Minneapolis, MN, 55455, USA. dannili@umn.edu.Department of Neurology and Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, 55902, USA.Department of Lab Medicine and Pathology, University of Minnesota, 420 Delaware Street SE, MMC 609, Minneapolis, MN, 55455, USA.Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, 55455, USA.Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, 55455, USA.University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA.School of Nursing, University of Minnesota, 5-140 WDH, 308 Harvard St SE, Minneapolis, MN, 55455, USA. yuxxx244@umn.edu.

Pub Type(s)

Clinical Trial Protocol
Journal Article

Language

eng

PubMed ID

31907024

Citation

Li, Danni, et al. "Blood Biomarkers as Surrogate Endpoints of Treatment Responses to Aerobic Exercise and Cognitive Training (ACT) in Amnestic Mild Cognitive Impairment: the Blood Biomarkers Study Protocol of a Randomized Controlled Trial (the ACT Trial)." Trials, vol. 21, no. 1, 2020, p. 19.
Li D, Mielke MM, Bell WR, et al. Blood biomarkers as surrogate endpoints of treatment responses to aerobic exercise and cognitive training (ACT) in amnestic mild cognitive impairment: the blood biomarkers study protocol of a randomized controlled trial (the ACT Trial). Trials. 2020;21(1):19.
Li, D., Mielke, M. M., Bell, W. R., Reilly, C., Zhang, L., Lin, F. V., & Yu, F. (2020). Blood biomarkers as surrogate endpoints of treatment responses to aerobic exercise and cognitive training (ACT) in amnestic mild cognitive impairment: the blood biomarkers study protocol of a randomized controlled trial (the ACT Trial). Trials, 21(1), 19. https://doi.org/10.1186/s13063-019-3798-1
Li D, et al. Blood Biomarkers as Surrogate Endpoints of Treatment Responses to Aerobic Exercise and Cognitive Training (ACT) in Amnestic Mild Cognitive Impairment: the Blood Biomarkers Study Protocol of a Randomized Controlled Trial (the ACT Trial). Trials. 2020 Jan 6;21(1):19. PubMed PMID: 31907024.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blood biomarkers as surrogate endpoints of treatment responses to aerobic exercise and cognitive training (ACT) in amnestic mild cognitive impairment: the blood biomarkers study protocol of a randomized controlled trial (the ACT Trial). AU - Li,Danni, AU - Mielke,Michelle M, AU - Bell,W Robert, AU - Reilly,Cavan, AU - Zhang,Lin, AU - Lin,Feng Vankee, AU - Yu,Fang, Y1 - 2020/01/06/ PY - 2019/07/17/received PY - 2019/10/11/accepted PY - 2020/1/8/entrez PY - 2020/1/8/pubmed PY - 2020/11/18/medline KW - Aerobic exercise KW - Alzheimer’s disease KW - Blood biomarkers KW - Cognitive training KW - Neurodegenerative biomarkers KW - Neuropathological biomarkers KW - Neurotrophic biomarkers KW - Surrogate endpoints KW - Treatment responses and amnestic mild cognitive impairment SP - 19 EP - 19 JF - Trials JO - Trials VL - 21 IS - 1 N2 - BACKGROUND: Alzheimer's disease (AD) is an epidemic with tremendous public health impacts because there are currently no disease-modifying therapeutics. Randomized controlled trials (RCTs) for prevention of AD dementia often use clinical endpoints that take years to manifest (e.g., cognition) or surrogate endpoints that are costly or invasive (e.g., magnetic resonance imaging [MRI]). Blood biomarkers represent a clinically applicable alternative surrogate endpoint for RCTs that would be both cost-effective and minimally invasive, but little is known about their value as surrogate endpoints for treatment responses in the prevention of AD dementia. METHODS: The objective of this study is to investigate blood neuropathological, neurodegenerative, and neurotrophic biomarkers as surrogate endpoints for treatment responses to three interventions in older adults with amnestic mild cognitive impairment (aMCI, a prodromal stage of AD): aerobic exercise, cognitive training, and combined aerobic exercise and cognitive training (ACT). We chose these three sets of biomarkers for their unique mechanistic associations with AD pathology, neurodegeneration and neurogenesis. This study is built on the ACT Trial (1R01AG055469), a single-blinded, multi-site, 2 × 2 factorial phase II RCT that examines the synergistic effects of a 6-month ACT intervention on cognition and MRI biomarkers (AD-signature cortical thickness and hippocampal volume) (n = 128). In this ACT Trial blood biomarkers study, we will enroll 120 ACT Trial participants with aMCI and measure blood biomarkers at baseline and at 3, 6, 12, and 18 months. The goals are to (1) determine the effect of interventions on blood biomarkers over 6 months, (2) evaluate blood biomarkers as surrogate endpoints for predicting cognitive responses to interventions over 18 months, and (3, exploratory) examine blood biomarkers as surrogate endpoints for predicting brain MRI biomarker responses to interventions over 18 months. DISCUSSION: This study aims to identify new blood biomarkers that can track cognitive decline or AD-related brain atrophy among patients with aMCI subjected to a regimen of aerobic exercise and cognitive training. Findings from this study will drive the further use of blood biomarkers in developing effective prevention and treatment strategies for AD dementia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03313895. Registered on 18 October 2017. SN - 1745-6215 UR - https://www.unboundmedicine.com/medline/citation/31907024/Blood_biomarkers_as_surrogate_endpoints_of_treatment_responses_to_aerobic_exercise_and_cognitive_training__ACT__in_amnestic_mild_cognitive_impairment:_the_blood_biomarkers_study_protocol_of_a_randomized_controlled_trial__the_ACT_Trial__ DB - PRIME DP - Unbound Medicine ER -