Autophagy-Enhancers to Reduce Sleep Disturbances
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age55-75
SponsorUniversity Medicine Greifswald
About this trial
This clinical trial investigates the effects of spermidine supplementation on sleep quality and sleep-dependent memory consolidation in older adults with Subjective Cognitive Decline (SCD) or Mild Cognitive Impairment (MCI), two populations at increased risk of future cognitive decline and dementia. Impaired sleep has been identified as a modifiable factor contributing to cognitive decline, and interventions targeting sleep architecture could offer therapeutic potential to prevent or slow down this decline.
Spermidine is a naturally occurring polyamine found in foods such as wheat germ and soybeans. It induces autophagy, a cellular degradation and recycling process essential for neuronal maintenance and function. In animal studies, spermidine has been shown to improve memory performance, reduce neuroinflammation, and support mitochondrial health. Preliminary findings from human trials in individuals with SCD or MCI suggest potential cognitive benefits of spermidine, but results are not unequivocal, and the impact on sleep has not been systematically evaluated.
In this randomized, double-blind, placebo-controlled trial, 76 participants aged 55 to 75 years with SCD or MCI will receive either spermidine (6 mg/day) or a placebo for 12 weeks. Sleep will be evaluated using overnight EEG in a controlled laboratory setting, focusing on measures such as slow-wave sleep and sleep spindle activity. Memory performance will be assessed before and after the intervention using standardized neuropsychological testing. Numerical skills will be tested at baseline only to compare SCD and MCI participants with healthy controls.
Blood samples will be collected to quantify metabolic indicators, neurodegeneration-related biomarkers, and autophagy-associated proteins. A control group of 38 cognitively healthy individuals will undergo comparable sleep and cognitive assessments without receiving any supplementation.
The primary objective of the study is to characterize the impact of spermidine on sleep-dependent memory consolidation and to identify associated biological changes relevant to aging and neurodegeneration. The results may inform the development of non-pharmacological strategies aimed at preserving cognitive function in individuals at risk for dementia.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Men and women
Written consent to participate in the study
German at native speaker level
Age between 55 and 75 years
Disqualifiers
Patients who are unable to give informed consent
Polyamine intake via dietary supplements and/or participation in corresponding intervention studies
Dementia according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)
Any condition that impairs clinical or neuropsychological examination procedures
Trial design
Design model
Parallel
Treatments tested in this trial
Spermidine Supplementation
Dietary supplementsupplementation of 6 mg Spermidine per day across 3 doses
Dietary Placebo
Dietary supplementsupplementation of 6 mg Placebo per day across 3 doses (placebo consists of maltodextrin, rice extract microcrystalline cellulose mixture, citric acid (anhydrous), silicon oxide (precipitated, E551))
Treatment groups
76 Participants
are divided into 3 treatment groupsGroup A: Healthy elderly controlsNo intervention 0 interventions
Group B: Dietary PlaceboPlacebo comparator 1 intervention
Group C: Dietary SupplementExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Effects of spermidine supplementation on sleep quality as measured by electroencephalography (EEG) mean power spectra
Individual mean power spectra are calculated. Subsequently, the mean power is calculated in the following EEG bands: slow oscillations (0.5-1 Hz), low delta (1-1.5 Hz), delta (1-4 Hz), theta (4-8 Hz), and beta (15-25 Hz). For the spermidine effect, baseline and follow-up EEG data are compared with each other.
Time frame
baseline, 12-week follow-up2
Effects of spermidine supplementation on sleep quality as measured by sleep spindle count assessed from EEG
Individual mean power spectra are calculated. Subsequently, the mean power is calculated in the following EEG bands: slow frontal spindle (8-12 Hz), fast parietal spindle (12-15 Hz), and the number of slow frontal and fast parietal discrete spindles are counted. Spindle detection is performed based on an algorithm adopted from previous studies. For the spermidine effect, baseline and follow-up EEG data are compared with each other.
Time frame
baseline, 12-week follow-up3
Effects of spermidine supplementation on sleep quality as measured by sleep spindle power assessed from EEG
Individual mean power spectra are calculated. Subsequently, the mean power is calculated in the following EEG bands: slow frontal spindle (8-12 Hz), fast parietal spindle (12-15 Hz). Spindle power is analyzed as a further measure of spindle activity. Spindle detection is performed based on an algorithm adopted from previous studies. For the spermidine effect, baseline and follow-up EEG data are compared with each other.
Time frame
baseline, 12-week follow-up4
Effects of spermidine supplementation on sleep-related alertness as measured by computer-based task
The alertness task is trained at adaptation night and assessed at baseline and follow-up before and after sleep. It comprises two runs without and two runs with a prior warning tone. For the spermidine effect, baseline and follow-up task performances of SCD and MCI participants are compared with each other. Task performance is measured by speed (in ms) and hit/false or miss.
Time frame
baseline, 12-week follow-upSecondary outcomes
1
Differences in autophagy-related blood markers pre and post spermidine intervention in SCD and MCI as measured by polyamine concentration
concentration in nmol / mg Protein assessed via Peripheral Blood Mononuclear Cells (PBMCs)
Time frame
baseline, 2 weeks after baseline, 12-week follow-up2
Differences in sleep quality between SCD or MCI and healthy controls (HC) as measured by electroencephalography (EEG) mean power spectra
Individual mean power spectra are calculated. Subsequently, the mean power is calculated in the following EEG bands: slow oscillations (0.5-1 Hz), low delta (1-1.5 Hz), delta (1-4 Hz), theta (4-8 Hz), and beta (15-25 Hz). The differences between SCD / MCI and healthy controls are assessed from baseline EEG data.
Time frame
baseline data3
Differences in sleep quality between SCD or MCI and healthy controls (HC) as measured by sleep spindle count assessed from EEG
Individual mean power spectra are calculated. Subsequently, the mean power is calculated in the following EEG bands: slow frontal spindle (8-12 Hz), fast parietal spindle (12-15 Hz), and the number of slow frontal and fast parietal discrete spindles are counted. Spindle detection is performed based on an algorithm adopted from previous studies. The differences between SCD / MCI and healthy controls are assessed from baseline EEG data.
Time frame
baseline data4
Differences in sleep quality between SCD or MCI and healthy controls (HC) as measured by sleep spindle power assessed from EEG
Individual mean power spectra are calculated. Subsequently, the mean power is calculated in the following EEG bands: slow frontal spindle (8-12 Hz), fast parietal spindle (12-15 Hz). Spindle power is analyzed as a further measure of spindle activity. Spindle detection is performed based on an algorithm adopted from previous studies. The differences between SCD / MCI and healthy controls are assessed from baseline EEG data.
Time frame
baseline dataSponsors and contacts
Click on the lead sponsor to view all of their trials.
University Medicine Greifswald
Lead sponsor
Department of Experimental Neuroimmunology, University Medicine
Collaborator
Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald
Collaborator
Institute of Biology, Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin
Collaborator
Source ClinicalTrials.gov