Mild Cognitive Impairment Due to Alzheimer's DiseaseSpSleepNCT07383311
Autophagy-Enhancers to Reduce Sleep Disturbances
A study testing Spermidine Supplementation in people with Mild Cognitive Impairment Due to Alzheimer's Disease and Subjective Cognitive Decline (SCD), run by University Medicine Greifswald at 1 site in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 55 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment Due to Alzheimer's Disease, Subjective Cognitive Decline (SCD)
- What is being tested?
- Spermidine Supplementation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 1 siteGermany
- Study dates
- 28 Oct 2025to May 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and women
- Written consent to participate in the study
- German at native speaker level
- Age between 55 and 75 years
- Subjective Cognitive Decline operationalized as:
- Subjectively reported decline in cognitive function (particularly memory) despite objectively normal cognitive performance (e.g., WMS-LM)
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- Preservation of functional independence
- No dementia
- Men and women
- Written consent to participate in the study
- German at native speaker level
- Age between 55 and 75 years
- Mild cognitive impairment (MCI) operationalized as:
- A change in cognitive abilities reported by the patient, relatives or clinic staff (i.e. historical or observed evidence of deterioration over time)
- Objective evidence of memory impairment (at least 1.0 Standard Deviation (SD) below the normal range on the Wechsler Logical Memory Scale (WMS-LM)); other cognitive domains may also be affected (i.e. amnestic MCI and amnestic + MCI)
- Preservation of independence of functional abilities
- No dementia
- Men and women
- Written consent to participate in the study
- German at native speaker level
- Age between 55 and 75 years
- Subjective cognitive disorders are denied
Who cannot join
- 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
- Diabetes mellitus
- Polycystic ovary syndrome
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- Signs of epilepsy, focal brain lesion or head injury with loss of consciousness or immediate post-injury confusion
- Previous stroke
- Severe untreated medical problems or unstable medical condition
- Current major depressive episode
- Psychotic disorder
- Bipolar disorder
- Current or previous substance abuse
- Other neurodegenerative disease, e.g. Parkinson's disease
- Vascular dementia
- Alcohol abuse
- Participation in an interventional study in the last 3 months and during the entire study period
- Sleep disorders
- Taking medication that primarily affects the central nervous system (e.g. antipsychotics, antidepressants, benzodiazepines or any type of over-the-counter sleep-inducing medication such as valerian; anti-dementia medication)
- Known intolerances or allergies to wheat germ, gluten or histamine
- Subjects who are not able 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)
- Mild cognitive impairment (MCI), defined as described above in the patient inclusion criteria
- Any condition that interferes with clinical or neuropsychological examination procedures
- Diabetes mellitus
- Polycystic ovary syndrome
- Signs of epilepsy, focal brain lesion or head injury with loss of consciousness or immediate post-injury confusion
- Previous stroke
- Severe untreated medical problems or unstable medical condition
- Current major depressive episode
- Psychotic disorder
- Bipolar disorder
- Current or past substance abuse
- Other neurodegenerative disease, e.g. Parkinson's disease
- Vascular dementia
- Alcohol abuse
- Participation in an interventional study in the last 3 months and during the entire study period
- Sleep disorders
- Taking medication that primarily affects the central nervous system (e.g. antipsychotics, antidepressants, benzodiazepines or any type of over-the-counter sleep-inducing medication such as valerian; anti-dementia medication)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
Department of Neurology, University Medicine Greifswald
Greifswald, Mecklenburg-Vorpommern, 17475
Agnes Flöel, Prof. Dr., +49 (0)3834 86-6815, agnes.floeel@med.uni-greifswald.de
About this study
Official title: Autophagy-Enhancers to Reduce Sleep Disturbances: A Combined Approach
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.
Read more
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.
Read the detailed description
Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI) represent early stages along the continuum of cognitive decline preceding dementia. Individuals with SCD report persistent cognitive complaints despite normal performance on standardized cognitive testing, whereas MCI is characterized by objective cognitive impairment that does not yet interfere substantially with activities of daily living. Both conditions are associated with an elevated risk of progression to Alzheimer's disease and other dementias. Disruption of sleep architecture is increasingly implicated in the pathophysiology of neurodegenerative disorders, and early interventions targeting sleep-related mechanisms could help delay further cognitive decline. This clinical trial evaluates the effects of spermidine supplementation on sleep quality and sleep-dependent memory consolidation in older adults with SCD or MCI.
Following an adaptation night and an initial baseline sleep assessment with overnight electroencephalography (EEG), participants will be randomly assigned to either the spermidine or placebo group. The intervention consists of a daily oral dose of 6 mg spermidine (administered as three 2 mg sachets), continued over a 12-week period. The trial employs a randomized, double-blind, placebo-controlled design. Placebo sachets, identical in appearance and taste, contain only microcrystalline cellulose. After the 12-week supplementation period, participants will return for a second overnight EEG assessment.
A healthy control group (n=38), matched for age and sex, will undergo comparable baseline assessments but will not receive any intervention. These data will provide normative reference values for sleep and cognitive parameters.
The primary objective of the study is to assess the impact of spermidine on sleep architecture, measured via overnight polysomnography, with a specific focus on slow-wave sleep and sleep spindle activity, EEG markers associated with sleep-dependent memory consolidation and known to decline with age and neurodegeneration. Secondary outcomes include changes in memory consolidation (assessed using a battery of cognitive tasks that target declarative, procedural, and visuospatial memory domains), as well as numerical skills (tested via e.g., digit-letter-decision task, Berlin Numeracy Test). Testing occurs before and after each EEG night to evaluate overnight consolidation effects. All participants will wear actigraphs prior to both EEG nights to monitor sleep-wake cycles and physical activity.
Additional biological endpoints will examine changes in circulating neuropeptides, insulin-glucose homeostasis, and autophagy-related biomarkers. Blood samples are collected at each EEG session and two weeks after the start of supplementation. Physiological assessments include measurements of inflammatory markers (e.g., interleukin (IL)-6, tumor necrosis factor (TNF-α), neuroprotective factors (e.g., Neuropeptide Y, eukaryotic translation initiation factor 5A (eIF5A) hypusination), and metabolic indicators (e.g., fasting insulin, glucose, and lipid profiles).
Participants will undergo structural brain imaging using a 3-Tesla MRI scanner to exclude individuals with comorbid neurological conditions (e.g., prior stroke, other neurodegenerative diseases) and to assess brain morphology. Eligibility is determined through standardized pre-screening procedures, including clinical interviews and neuropsychological assessments.
The study includes 76 participants with SCD or MCI, aged 55-75 years, randomly allocated to either the spermidine or placebo group (n=38 per group). The sample size provides adequate statistical power to detect medium-to-large effect sizes, based on previous pilot findings and anticipated attrition rates.
This study aims to investigate the effects of spermidine supplementation on neurophysiological and cognitive outcomes in individuals with early-stage cognitive decline. The results are expected to contribute to the growing body of evidence evaluating spermidine as a safe, nutrition-based strategy for maintaining brain health and cognitive function in the context of aging.
- Being tested
- Spermidine Supplementation, Dietary Placebo
- Keywords
- Mild Cognitive Impairment, Autophagy, sleep, Spermidine, memory consolidation, electroencephalography, polysomnography, randomized controlled trial, subjective cognitive decline
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Spermidine SupplementationDietary supplement
supplementation of 6 mg Spermidine per day across 3 doses
Dietary PlaceboDietary supplement
supplementation 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))
| Study group | Role | What they receive |
|---|---|---|
| Healthy elderly controls | No intervention | baseline comparison, healthy controls are not part of the intervention |
| Dietary Placebo | Placebo comparator | Not described Receives: Dietary Supplement: Dietary Placebo |
| Dietary Supplement | Experimental | Not described Receives: Dietary Supplement: Spermidine Supplementation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline, 12-week follow-up
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.
Measured: baseline, 12-week follow-up
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.
Measured: baseline, 12-week follow-up
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.
Measured: baseline, 12-week follow-up
Effects of spermidine supplementation on sleep-related visual-spatial memory as measured by computer-based task
The visual-spatial memory task is trained at adaptation night and assessed at baseline and follow-up before and after sleep. After an encoding phase consisting of 60 objects (e.g., photo of a band-aid) placed in front of a background (e.g., photo of a treatment room in a doctor's office), a retrieval phase follows directly after encoding in the evening before bedtime, in which 30 randomly selected images from the total of 60 are tested. Participants should memorize the position of the object placed in front of the background and select the correct position by pressing a button.
In the next morning, the remaining 30 images are tested in a recall phase.
Task performance is measured by speed (in ms) and hit/false or miss.
For the spermidine effect, baseline and follow-up task performances of SCD and MCI participants are compared with each other.
Measured: baseline, 12-week follow-up
Effects of spermidine supplementation on sleep-related verbal memory as measured by computer-based task
The verbal memory task is trained at adaptation night and assessed at baseline and follow-up before and after sleep. After an encoding phase consisting of 44 word pairs, a retrieval phase follows directly after encoding in the evening before bedtime, in which all word pairs are tested in randomized order. The next morning, all word pairs are tested in a recall phase.
Task performance is measured by hit/false or miss.
For the spermidine effect, baseline and follow-up task performances of SCD and MCI participants are compared with each other.
Measured: baseline, 12-week follow-up
Secondary outcomes (14)
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)
Measured: baseline, 2 weeks after baseline, 12-week follow-up
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.
Measured: baseline data
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.
Measured: baseline data
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.
Measured: baseline data
Differences in autophagy-related blood markers pre and post spermidine intervention in SCD or MCI as measured by eIF5A hypusination
assessed via Hypusinated eIF5A levels (Western Blot) from Peripheral Blood Mononuclear Cells (PBMCs)
Measured: baseline, 2 weeks after baseline, 12-week follow-up
Differences in neuropeptide Y blood levels pre and post spermidine intervention in SCD or MCI
Neuropeptide Y blood levels in pg/ml analyzed from serum blood sample
Measured: baseline, 12-week follow-up
Differences in sleep-related alertness between SCD or MCI participants and healthy controls 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.
The differences between SCD / MCI and healthy controls are assessed from baseline task data. Task performance is measured by speed (in ms) and hit/false or miss.
Measured: baseline
Differences in sleep-related visual-spatial memory between SCD or MCI participants and healthy controls as measured by computer-based task
The visual-spatial memory task is trained at adaptation night and assessed at baseline and follow-up before and after sleep. After an encoding phase consisting of 60 objects (e.g., photo of a band-aid) placed in front of a background (e.g., photo of a treatment room in a doctor's office), a retrieval phase follows directly after encoding in the evening before bedtime, in which 30 randomly selected images from the total of 60 are tested. Participants should memorize the position of the object placed in front of the background and select the correct position by pressing a button.
In the next morning, the remaining 30 images are tested in a recall phase.
Task performance is measured by speed (in ms) and hit/false or miss.
The differences between SCD / MCI and healthy controls are assessed from baseline task data.
Measured: baseline
Differences in sleep-related verbal memory between SCD or MCI participants and healthy controls as measured by computer-based task
The verbal memory task is trained at adaptation night and assessed at baseline and follow-up before and after sleep. After an encoding phase consisting of 44 word pairs, a retrieval phase follows directly after encoding in the evening before bedtime, in which all word pairs are tested in randomized order. The next morning, all word pairs are tested in a recall phase.
Task performance is measured by hit/false or miss.
The differences between SCD / MCI and healthy controls are assessed from baseline task data.
Measured: baseline
Differences in neuropeptide Y blood levels between SCD or MCI and healthy controls
blood levels in pg/ml analyzed from serum blood sample
Measured: baseline data
Differences in autophagy-related blood markers between SCD or MCI and healthy controls as measured by polyamine concentration
concentration in nmol / mg Protein assessed via Peripheral Blood Mononuclear Cells (PBMCs)
Measured: baseline data
Differences in autophagy-related blood markers between SCD or MCI and healthy controls as measured by eIF5A hypusination
assessed via Hypusinated eIF5A levels (Western Blot) from Peripheral Blood Mononuclear Cells (PBMCs)
Measured: baseline data
Differences in numerical skills between SCD or MCI patients and healthy controls as measured by lexical decision task
Participants complete a computer-based lexical decision task, in which a row of six symbols is presented after a fixation cross. Depending on the condition, the test subjects must decide by pressing a key on the keyboard whether the row presented contains a letter (e.g., condition 1) or a digit (e.g., condition 2). Each condition consists of two blocks. After the first block, there is a short pause before the second block starts. The condition (digit or letter) with which the trial starts is randomized for each test subject.
Measured: assessed at baseline only
Differences in numerical skills between SCD or MCI participants and healthy controls as measured by Berlin Numeracy Test
The Berlin Numeracy Test contains 4 short, text-based questions testing statistical numeracy and risk literacy, requiring Bayesian inference for problems like understanding probabilities in health concerns (e.g., poisonous mushrooms) or lotteries, often presenting data in relative/absolute numbers and asking for probability estimates. Correct answers scored for a total of 0-4 points.
Measured: assessed at baseline only
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2026
- Study start28 Oct 2025
- Primary completionDec 2028 (estimated)
- Study completionMay 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive Impairment Due to Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 76 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medicine Greifswald
- Sponsor type
- University, hospital or other
- Collaborators
- Department of Experimental Neuroimmunology, University Medicine, Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Institute of Biology, Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin
- Responsible party
- Principal investigator, Nina Unger, University Medicine Greifswald
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07383311
- Sponsor's protocol ID
- Autophagy and Sleep
- Other IDs
- 508402643
- Acronym
- SpSleep
- Status last verified
- Jun 2026
- First submitted
- 17 Sep 2025
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Marshall L, Helgadottir H, Molle M, Born J. Boosting slow oscillations during sleep potentiates memory. Nature. 2006 Nov 30;444(7119):610-3. doi: 10.1038/nature05278. Epub 2006 Nov 5.
PubMed 17086200Gupta VK, Pech U, Bhukel A, Fulterer A, Ender A, Mauermann SF, Andlauer TF, Antwi-Adjei E, Beuschel C, Thriene K, Maglione M, Quentin C, Bushow R, Schwarzel M, Mielke T, Madeo F, Dengjel J, Fiala A, Sigrist SJ. Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release. PLoS Biol. 2016 Sep 29;14(9):e1002563. doi: 10.1371/journal.pbio.1002563. eCollection 2016 Sep.
PubMed 27684064Minois N, Carmona-Gutierrez D, Madeo F. Polyamines in aging and disease. Aging (Albany NY). 2011 Aug;3(8):716-32. doi: 10.18632/aging.100361.
PubMed 21869457Madeo F, Eisenberg T, Pietrocola F, Kroemer G. Spermidine in health and disease. Science. 2018 Jan 26;359(6374):eaan2788. doi: 10.1126/science.aan2788.
PubMed 29371440
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autophagy-Enhancers to Reduce Sleep Disturbances: A Combined Approach
- ClinicalTrials.gov ID
- NCT07383311
- Acronym / sponsor ID
- SpSleep / Autophagy and Sleep
- Keywords
- Mild Cognitive Impairment, Autophagy, sleep, Spermidine, memory consolidation, electroencephalography, polysomnography, randomized controlled trial
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 76 participants (estimated)
- Lead sponsor
- University Medicine GreifswaldUniversity, hospital or other
- Collaborators
- Department of Experimental Neuroimmunology, University Medicine, Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Institute of Biology, Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin
- Study start
- 28 Oct 2025 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- May 2029 (estimated)
- First posted
- 3 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI) represent early stages along the continuum of cognitive decline preceding dementia. Individuals with SCD report persistent cognitive complaints despite normal performance on standardized cognitive testing, whereas MCI is characterized by objective cognitive impairment that does not yet interfere substantially with activities of daily living. Both conditions are associated with an elevated risk of progression to Alzheimer's disease and other dementias. Disruption of sleep architecture is increasingly implicated in the pathophysiology of neurodegenerative disorders, and early interventions targeting sleep-related mechanisms could help delay further cognitive decline. This clinical trial evaluates the effects of spermidine supplementation on sleep quality and sleep-dependent memory consolidation in older adults with SCD or MCI.
Following an adaptation night and an initial baseline sleep assessment with overnight electroencephalography (EEG), participants will be randomly assigned to either the spermidine or placebo group. The intervention consists of a daily oral dose of 6 mg spermidine (administered as three 2 mg sachets), continued over a 12-week period. The trial employs a randomized, double-blind, placebo-controlled design. Placebo sachets, identical in appearance and taste, contain only microcrystalline cellulose. After the 12-week supplementation period, participants will return for a second overnight EEG assessment.
A healthy control group (n=38), matched for age and sex, will undergo comparable baseline assessments but will not receive any intervention. These data will provide normative reference values for sleep and cognitive parameters.
The primary objective of the study is to assess the impact of spermidine on sleep architecture, measured via overnight polysomnography, with a specific focus on slow-wave sleep and sleep spindle activity, EEG markers associated with sleep-dependent memory consolidation and known to decline with age and neurodegeneration. Secondary outcomes include changes in memory consolidation (assessed using a battery of cognitive tasks that target declarative, procedural, and visuospatial memory domains), as well as numerical skills (tested via e.g., digit-letter-decision task, Berlin Numeracy Test). Testing occurs before and after each EEG night to evaluate overnight consolidation effects. All participants will wear actigraphs prior to both EEG nights to monitor sleep-wake cycles and physical activity.
Additional biological endpoints will examine changes in circulating neuropeptides, insulin-glucose homeostasis, and autophagy-related biomarkers. Blood samples are collected at each EEG session and two weeks after the start of supplementation. Physiological assessments include measurements of inflammatory markers (e.g., interleukin (IL)-6, tumor necrosis factor (TNF-α), neuroprotective factors (e.g., Neuropeptide Y, eukaryotic translation initiation factor 5A (eIF5A) hypusination), and metabolic indicators (e.g., fasting insulin, glucose, and lipid profiles).
Participants will undergo structural brain imaging using a 3-Tesla MRI scanner to exclude individuals with comorbid neurological conditions (e.g., prior stroke, other neurodegenerative diseases) and to assess brain morphology. Eligibility is determined through standardized pre-screening procedures, including clinical interviews and neuropsychological assessments.
The study includes 76 participants with SCD or MCI, aged 55-75 years, randomly allocated to either the spermidine or placebo group (n=38 per group). The sample size provides adequate statistical power to detect medium-to-large effect sizes, based on previous pilot findings and anticipated attrition rates.
This study aims to investigate the effects of spermidine supplementation on neurophysiological and cognitive outcomes in individuals with early-stage cognitive decline. The results are expected to contribute to the growing body of evidence evaluating spermidine as a safe, nutrition-based strategy for maintaining brain health and cognitive function in the context of aging.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy elderly controls | No intervention | –baseline comparison, healthy controls are not part of the intervention |
| Dietary Placebo | Placebo comparator | Dietary Supplement: Dietary Placebo |
| Dietary Supplement | Experimental | Dietary Supplement: Spermidine Supplementation |
Who may qualify
- Ages
- 55 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Men and women
- Written consent to participate in the study
- German at native speaker level
- Age between 55 and 75 years
- Subjective Cognitive Decline operationalized as:
Key exclusion criteria (40 listed)
- 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
- Diabetes mellitus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Spermidine Supplementationsupplementation of 6 mg Spermidine per day across 3 doses | Dietary supplement | Dietary Supplement |
| Dietary Placebosupplementation 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)) | Dietary supplement | Dietary Placebo |
Primary outcome
Effects of spermidine supplementation on sleep quality as measured by electroencephalography (EEG) mean power spectra
Time frame: baseline, 12-week follow-up
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.
Effects of spermidine supplementation on sleep quality as measured by sleep spindle count assessed from EEG
Time frame: baseline, 12-week follow-up
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.
Effects of spermidine supplementation on sleep quality as measured by sleep spindle power assessed from EEG
Time frame: baseline, 12-week follow-up
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.
Effects of spermidine supplementation on sleep-related alertness as measured by computer-based task
Time frame: baseline, 12-week follow-up
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.
Effects of spermidine supplementation on sleep-related visual-spatial memory as measured by computer-based task
Time frame: baseline, 12-week follow-up
The visual-spatial memory task is trained at adaptation night and assessed at baseline and follow-up before and after sleep. After an encoding phase consisting of 60 objects (e.g., photo of a band-aid) placed in front of a background (e.g., photo of a treatment room in a doctor's office), a retrieval phase follows directly after encoding in the evening before bedtime, in which 30 randomly selected images from the total of 60 are tested. Participants should memorize the position of the object placed in front of the background and select the correct position by pressing a button. In the next morning, the remaining 30 images are tested in a recall phase. Task performance is measured by speed (in ms) and hit/false or miss. For the spermidine effect, baseline and follow-up task performances of SCD and MCI participants are compared with each other.
Effects of spermidine supplementation on sleep-related verbal memory as measured by computer-based task
Time frame: baseline, 12-week follow-up
The verbal memory task is trained at adaptation night and assessed at baseline and follow-up before and after sleep. After an encoding phase consisting of 44 word pairs, a retrieval phase follows directly after encoding in the evening before bedtime, in which all word pairs are tested in randomized order. The next morning, all word pairs are tested in a recall phase. Task performance is measured by hit/false or miss. For the spermidine effect, baseline and follow-up task performances of SCD and MCI participants are compared with each other.
14 secondary outcomes
Differences in autophagy-related blood markers pre and post spermidine intervention in SCD and MCI as measured by polyamine concentration
Time frame: baseline, 2 weeks after baseline, 12-week follow-up
Differences in sleep quality between SCD or MCI and healthy controls (HC) as measured by electroencephalography (EEG) mean power spectra
Time frame: baseline data
Differences in sleep quality between SCD or MCI and healthy controls (HC) as measured by sleep spindle count assessed from EEG
Time frame: baseline data
Differences in sleep quality between SCD or MCI and healthy controls (HC) as measured by sleep spindle power assessed from EEG
Time frame: baseline data
Differences in autophagy-related blood markers pre and post spermidine intervention in SCD or MCI as measured by eIF5A hypusination
Time frame: baseline, 2 weeks after baseline, 12-week follow-up
Differences in neuropeptide Y blood levels pre and post spermidine intervention in SCD or MCI
Time frame: baseline, 12-week follow-up
Differences in sleep-related alertness between SCD or MCI participants and healthy controls as measured by computer-based task
Time frame: baseline
Differences in sleep-related visual-spatial memory between SCD or MCI participants and healthy controls as measured by computer-based task
Time frame: baseline
Differences in sleep-related verbal memory between SCD or MCI participants and healthy controls as measured by computer-based task
Time frame: baseline
Differences in neuropeptide Y blood levels between SCD or MCI and healthy controls
Time frame: baseline data
Differences in autophagy-related blood markers between SCD or MCI and healthy controls as measured by polyamine concentration
Time frame: baseline data
Differences in autophagy-related blood markers between SCD or MCI and healthy controls as measured by eIF5A hypusination
Time frame: baseline data
Differences in numerical skills between SCD or MCI patients and healthy controls as measured by lexical decision task
Time frame: assessed at baseline only
Differences in numerical skills between SCD or MCI participants and healthy controls as measured by Berlin Numeracy Test
Time frame: assessed at baseline only
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Background: PubMed 17086200Marshall L, Helgadottir H, Molle M, Born J. Boosting slow oscillations during sleep potentiates memory. Nature. 2006 Nov 30;444(7119):610-3. doi: 10.1038/nature05278. Epub 2006 Nov 5.
- Background: PubMed 27684064Gupta VK, Pech U, Bhukel A, Fulterer A, Ender A, Mauermann SF, Andlauer TF, Antwi-Adjei E, Beuschel C, Thriene K, Maglione M, Quentin C, Bushow R, Schwarzel M, Mielke T, Madeo F, Dengjel J, Fiala A, Sigrist SJ. Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release. PLoS Biol. 2016 Sep 29;14(9):e1002563. doi: 10.1371/journal.pbio.1002563. eCollection 2016 Sep.
- Background: PubMed 21869457Minois N, Carmona-Gutierrez D, Madeo F. Polyamines in aging and disease. Aging (Albany NY). 2011 Aug;3(8):716-32. doi: 10.18632/aging.100361.
- Background: PubMed 29371440Madeo F, Eisenberg T, Pietrocola F, Kroemer G. Spermidine in health and disease. Science. 2018 Jan 26;359(6374):eaan2788. doi: 10.1126/science.aan2788.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Spermidine Supplementation in people with Mild Cognitive Impairment Due to Alzheimer's Disease and Subjective Cognitive Decline (SCD), run by University Medicine Greifswald at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Agnes Flöel, Prof. Dr. (+49 (0)3834 86-6815, agnes.floeel@med.uni-greifswald.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effects of spermidine supplementation on sleep quality as measured by electroencephalography (EEG) mean power spectra (time frame: baseline, 12-week follow-up). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07383311, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.