Clinical Trial

. 2019 May 1;11(1):36.

doi: 10.1186/s13195-019-0484-1.

Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)-study protocol for a randomized controlled trial

Miranka Wirth^#^{1

2

3

4}, Claudia Schwarz^#^{1

2}, Gloria Benson^#^{1

2}, Nora Horn^{1

2}, Ralph Buchert^{5

6}, Catharina Lange⁵, Theresa Köbe^{1

2

7

8}, Stefan Hetzer^{9

10}, Marta Maglione^{2

11}, Eva Michael^{2

11}, Stefanie Märschenz², Knut Mai^{12

13}, Ute Kopp¹, Dietmar Schmitz^{2

14}, Ulrike Grittner^{15

16}, Stephan J Sigrist^{2

11

14}, Slaven Stekovic¹⁷, Frank Madeo^{18

19}, Agnes Flöel^{20

21}

Affiliations

¹ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik und Hochschulambulanz für Neurologie, Berlin, Germany.
² Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Clinical Research Center, Berlin, Germany.
³ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Research Berlin, Berlin, Germany.
⁴ German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.
⁵ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Nuclear Medicine, Berlin, Germany.
⁶ University Hospital Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Hamburg, Germany.
⁷ Douglas Mental Health University Institute, Studies on Prevention of Alzheimer's Disease (StOP-AD) Centre, Montreal, Quebec, Canada.
⁸ Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
⁹ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin Center for Advanced Neuroimaging, Berlin, Germany.
¹⁰ Bernstein Center for Computational Neuroscience, Berlin, Germany.
¹¹ Institute for Biology/Genetics, Freie Universität Berlin, Berlin, Germany.
¹² Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology & Metabolism, Berlin, Germany.
¹³ Charité-Center for Cardiovascular Research (CCR), Berlin, Germany.
¹⁴ German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
¹⁵ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Berlin, Germany.
¹⁶ Berlin Institute of Health (BIH), Berlin, Germany.
¹⁷ Institute of Molecular Biosciences, University of Graz, NAWI Graz, Graz, Austria.
¹⁸ Institute of Molecular Biosciences, University of Graz, NAWI Graz, Graz, Austria. frank.madeo@uni-graz.at.
¹⁹ BioTechMed, Graz, Austria. frank.madeo@uni-graz.at.
²⁰ Department of Neurology, University Medicine Greifswald, Greifswald, Germany. agnes.floeel@uni-greifswald.de.
²¹ German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Rostock, Germany. agnes.floeel@uni-greifswald.de.

^# Contributed equally.

PMID: 31039826
PMCID: PMC6492385
DOI: 10.1186/s13195-019-0484-1

Clinical Trial

Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)-study protocol for a randomized controlled trial

Miranka Wirth et al. Alzheimers Res Ther. 2019.

. 2019 May 1;11(1):36.

doi: 10.1186/s13195-019-0484-1.

Authors

Affiliations

¹ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik und Hochschulambulanz für Neurologie, Berlin, Germany.
² Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Clinical Research Center, Berlin, Germany.
³ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Research Berlin, Berlin, Germany.
⁴ German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.
⁵ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Nuclear Medicine, Berlin, Germany.
⁶ University Hospital Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Hamburg, Germany.
⁷ Douglas Mental Health University Institute, Studies on Prevention of Alzheimer's Disease (StOP-AD) Centre, Montreal, Quebec, Canada.
⁸ Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
⁹ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin Center for Advanced Neuroimaging, Berlin, Germany.
¹⁰ Bernstein Center for Computational Neuroscience, Berlin, Germany.
¹¹ Institute for Biology/Genetics, Freie Universität Berlin, Berlin, Germany.
¹² Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology & Metabolism, Berlin, Germany.
¹³ Charité-Center for Cardiovascular Research (CCR), Berlin, Germany.
¹⁴ German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
¹⁵ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Berlin, Germany.
¹⁶ Berlin Institute of Health (BIH), Berlin, Germany.
¹⁷ Institute of Molecular Biosciences, University of Graz, NAWI Graz, Graz, Austria.
¹⁸ Institute of Molecular Biosciences, University of Graz, NAWI Graz, Graz, Austria. frank.madeo@uni-graz.at.
¹⁹ BioTechMed, Graz, Austria. frank.madeo@uni-graz.at.
²⁰ Department of Neurology, University Medicine Greifswald, Greifswald, Germany. agnes.floeel@uni-greifswald.de.
²¹ German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Rostock, Germany. agnes.floeel@uni-greifswald.de.

^# Contributed equally.

PMID: 31039826
PMCID: PMC6492385
DOI: 10.1186/s13195-019-0484-1

Erratum in

Correction: Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)-study protocol for a randomized controlled trial.
Wirth M, Schwarz C, Benson G, Horn N, Buchert R, Lange C, Köbe T, Hetzer S, Maglione M, Michael E, Märschenz S, Mai K, Kopp U, Schmitz D, Grittner U, Sigrist SJ, Stekovic S, Madeo F, Flöel A. Wirth M, et al. Alzheimers Res Ther. 2022 Jun 11;14(1):81. doi: 10.1186/s13195-022-01012-9. Alzheimers Res Ther. 2022. PMID: 35690844 Free PMC article. No abstract available.

Abstract

Background: Given the global increase in the aging population and age-related diseases, the promotion of healthy aging is one of the most crucial public health issues. This trial aims to contribute to the establishment of effective approaches to promote cognitive and brain health in older individuals with subjective cognitive decline (SCD). Presence of SCD is known to increase the risk of objective cognitive decline and progression to dementia due to Alzheimer's disease. Therefore, it is our primary goal to determine whether spermidine supplementation has a positive impact on memory performance in this at-risk group, as compared with placebo. The secondary goal is to examine the effects of spermidine intake on other neuropsychological, behavioral, and physiological parameters.

Methods: The SmartAge trial is a monocentric, randomized, double-blind, placebo-controlled phase IIb trial. The study will investigate 12 months of intervention with spermidine-based nutritional supplementation (target intervention) compared with 12 months of placebo intake (control intervention). We plan to recruit 100 cognitively normal older individuals with SCD from memory clinics, neurologists and general practitioners in private practice, and the general population. Participants will be allocated to one of the two study arms using blockwise randomization stratified by age and sex with a 1:1 allocation ratio. The primary outcome is the change in memory performance between baseline and post-intervention visits (12 months after baseline). Secondary outcomes include the change in memory performance from baseline to follow-up assessment (18 months after baseline), as well as changes in neurocognitive, behavioral, and physiological parameters (including blood and neuroimaging biomarkers), assessed at baseline and post-intervention.

Discussion: The SmartAge trial aims to provide evidence of the impact of spermidine supplementation on memory performance in older individuals with SCD. In addition, we will identify possible neurophysiological mechanisms of action underlying the anticipated cognitive benefits. Overall, this trial will contribute to the establishment of nutrition intervention in the prevention of Alzheimer's disease.

Trial registration: ClinicalTrials.gov, NCT03094546 . Registered 29 March 2017-retrospectively registered.

Protocol version: Based on EA1/250/16 version 1.5.

Keywords: Aging; Autophagy; Dietary supplementation; Health; Memory; Nutrition; Polyamines.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

The study protocol, participant information sheet, and participant informed consent were submitted for ethical review and have received approval from the Ethics Committee of the Charité – Universitätsmedizin, Berlin, Germany (EA1/ 250 /16, date of first approval: 13.10.2016). The FBB PET measurements were approved by the Federal Radiation Protection Authority (Bundesamt für Strahlenschutz (BfS)) Salzgitter Germany (Z5 – 22461/2 – 2016-010, date of approval: 17.07.2017). All procedures conducted during the SmartAge trial will be carried out in compliance with the Declaration of Helsinki.

Consent for publication

Not applicable

Competing interests

Slaven Stekovic, Stephan J. Sigrist, and Frank Madeo have a financial interest in TLL. All other authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
SmartAge study flowchart. Abbreviations: MRI: magnetic resonance imaging; *PET* positron emission tomography, *SCD* subjective cognitive decline

See this image and copyright information in PMC

References

1. United Nations DoEaSA, Population Division;: World Population Ageing. New York: United Nations; 2015.
1. Prince M, Wimo A, Guerchet M, Ali G, Wu Y, Prina M. World Alzheimer report 2015—the global impact of dementia: an analysis of prevalence, incidence, cost and trends. London; 2015.
1. Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C. Potential for primary prevention of Alzheimer's disease: an analysis of population-based data. Lancet Neurol. 2014;13:788–794. doi: 10.1016/S1474-4422(14)70136-X. - DOI - PubMed
1. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR, Jr, Kaye J, Montine TJ, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s Dementia. 2011;7:280–292. doi: 10.1016/j.jalz.2011.03.003. - DOI - PMC - PubMed
1. Jack CR, Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010;9:119–128. doi: 10.1016/S1474-4422(09)70299-6. - DOI - PMC - PubMed

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Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)-study protocol for a randomized controlled trial

Affiliations

Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)-study protocol for a randomized controlled trial

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Figures

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical