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Potenziatori dell'Autofagia per Ridurre i Disturbi del Sonno (SpSleep)

28 settembre 2026 aggiornato da: Nina Unger, University Medicine Greifswald

Autofagia-Potenziatori per Ridurre i Disturbi del Sonno: Un Approccio Combinato

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.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Stimato)

76

Fase

  • Non applicabile

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

  • Germania
    • Mecklenburg-Vorpommern
      • Greifswald, Mecklenburg-Vorpommern, Germania, 17475
        • Reclutamento
        • Department of Neurology, University Medicine Greifswald
        • Contatto:

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 55 anni a 75 anni (Adulto, Adulto più anziano)

Accetta volontari sani

Sì

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria (SCD participants):

  • 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:

    1. Subjectively reported decline in cognitive function (particularly memory) despite objectively normal cognitive performance (e.g., WMS-LM)
    2. Preservation of functional independence
    3. No dementia

Inclusion Criteria (MCI patients):

  • 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:

    1. A change in cognitive abilities reported by the patient, relatives or clinic staff (i.e. historical or observed evidence of deterioration over time)
    2. 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)
    3. Preservation of independence of functional abilities
    4. No dementia

Exclusion Criteria (SCD and MCI participants):

  • 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
  • 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

Inclusion criteria (healthy controls):

  • 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

Exclusion criteria (healthy controls):

  • 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)

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Scienza basilare
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Doppio

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Supplemento dietetico
Integratore alimentare: Spermidine Supplementation

supplementation of 6 mg Spermidine per day across 3 doses
Comparatore placebo: Dietary Placebo
Integratore alimentare: Dietary Placebo

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))
Nessun intervento: Healthy elderly controls

baseline comparison, healthy controls are not part of the intervention

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Effects of spermidine supplementation on sleep quality as measured by electroencephalography (EEG) mean power spectra
Lasso di tempo: 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.
baseline, 12-week follow-up
Effects of spermidine supplementation on sleep quality as measured by sleep spindle count assessed from EEG
Lasso di tempo: 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.
baseline, 12-week follow-up
Effects of spermidine supplementation on sleep quality as measured by sleep spindle power assessed from EEG
Lasso di tempo: 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.
baseline, 12-week follow-up
Effects of spermidine supplementation on sleep-related alertness as measured by computer-based task
Lasso di tempo: 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.
baseline, 12-week follow-up
Effects of spermidine supplementation on sleep-related visual-spatial memory as measured by computer-based task
Lasso di tempo: 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.
baseline, 12-week follow-up
Effects of spermidine supplementation on sleep-related verbal memory as measured by computer-based task
Lasso di tempo: 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.
baseline, 12-week follow-up

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Differences in autophagy-related blood markers pre and post spermidine intervention in SCD and MCI as measured by polyamine concentration
Lasso di tempo: baseline, 2 weeks after baseline, 12-week follow-up

concentration in nmol / mg Protein assessed via Peripheral Blood Mononuclear Cells (PBMCs)
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
Lasso di tempo: baseline data

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.
baseline data
Differences in sleep quality between SCD or MCI and healthy controls (HC) as measured by sleep spindle count assessed from EEG
Lasso di tempo: baseline data

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.
baseline data
Differences in sleep quality between SCD or MCI and healthy controls (HC) as measured by sleep spindle power assessed from EEG
Lasso di tempo: baseline data

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.
baseline data
Differences in autophagy-related blood markers pre and post spermidine intervention in SCD or MCI as measured by eIF5A hypusination
Lasso di tempo: baseline, 2 weeks after baseline, 12-week follow-up

assessed via Hypusinated eIF5A levels (Western Blot) from Peripheral Blood Mononuclear Cells (PBMCs)
baseline, 2 weeks after baseline, 12-week follow-up
Differences in neuropeptide Y blood levels pre and post spermidine intervention in SCD or MCI
Lasso di tempo: baseline, 12-week follow-up

Neuropeptide Y blood levels in pg/ml analyzed from serum blood sample
baseline, 12-week follow-up
Differences in sleep-related alertness between SCD or MCI participants and healthy controls as measured by computer-based task
Lasso di tempo: baseline

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.
baseline
Differences in sleep-related visual-spatial memory between SCD or MCI participants and healthy controls as measured by computer-based task
Lasso di tempo: baseline

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.
baseline
Differences in sleep-related verbal memory between SCD or MCI participants and healthy controls as measured by computer-based task
Lasso di tempo: baseline

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.
baseline
Differences in neuropeptide Y blood levels between SCD or MCI and healthy controls
Lasso di tempo: baseline data

blood levels in pg/ml analyzed from serum blood sample
baseline data
Differences in autophagy-related blood markers between SCD or MCI and healthy controls as measured by polyamine concentration
Lasso di tempo: baseline data

concentration in nmol / mg Protein assessed via Peripheral Blood Mononuclear Cells (PBMCs)
baseline data
Differences in autophagy-related blood markers between SCD or MCI and healthy controls as measured by eIF5A hypusination
Lasso di tempo: baseline data

assessed via Hypusinated eIF5A levels (Western Blot) from Peripheral Blood Mononuclear Cells (PBMCs)
baseline data
Differences in numerical skills between SCD or MCI patients and healthy controls as measured by lexical decision task
Lasso di tempo: assessed at baseline only

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.
assessed at baseline only
Differences in numerical skills between SCD or MCI participants and healthy controls as measured by Berlin Numeracy Test
Lasso di tempo: assessed at baseline only

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.
assessed at baseline only

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

University Medicine Greifswald

Collaboratori

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

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

28 ottobre 2025

Completamento primario (Stimato)

1 dicembre 2028

Completamento dello studio (Stimato)

1 maggio 2029

Date di iscrizione allo studio

Primo inviato

17 settembre 2025

Primo inviato che soddisfa i criteri di controllo qualità

28 gennaio 2026

Primo Inserito (Effettivo)

3 febbraio 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

2 ottobre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

28 settembre 2026

Ultimo verificato

1 giugno 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • Autophagy and Sleep
  • 508402643 (Altro numero di sovvenzione/finanziamento: Deutsche Forschungsgemeinschaft (DFG))

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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