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, Claudia Schwarz, Gloria Benson, Nora Horn, Ralph Buchert, Catharina Lange, Theresa Köbe, Stefan Hetzer, Marta Maglione, Eva Michael, Stefanie Märschenz, Knut Mai, Ute Kopp, Dietmar Schmitz, Ulrike Grittner, Stephan J Sigrist, Slaven Stekovic, Frank Madeo, Agnes Flöel, Miranka Wirth, Claudia Schwarz, Gloria Benson, Nora Horn, Ralph Buchert, Catharina Lange, Theresa Köbe, Stefan Hetzer, Marta Maglione, Eva Michael, Stefanie Märschenz, Knut Mai, Ute Kopp, Dietmar Schmitz, Ulrike Grittner, Stephan J Sigrist, Slaven Stekovic, Frank Madeo, Agnes Flöel

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.

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

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