Autophagy-Enhancers to Reduce Sleep Disturbances

NCT07383311 | Recruiting

• 2 other identifiers: Autophagy and Sleep508402643
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial investigates the effects of spermidine supplementation on sleep quality and memory function in older adults with Mild Cognitive Impairment (MCI), a condition associated with an increased risk of developing dementia, particularly in patients with MCI due to Alzheimer's disease. 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 subjective cognitive decline 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 70 years with 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 MCI patients 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.

Conditions

Mild Cognitive Impairment Due to Alzheimer's Disease

Keywords

Mild Cognitive Impairment; Autophagy; sleep; Spermidine; memory consolidation; electroencephalography; polysomnography; randomized controlled trial

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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 MCI patients 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

  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 MCI patients 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

  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 MCI patients are compared with each other.

  baseline, 12-week follow-up

Secondary Outcomes (14)

• Differences in autophagy-related blood markers pre and post spermidine intervention in MCI as measured by polyamine concentration

  baseline, 2 weeks after baseline, 12-week follow-up

• Differences in sleep quality between MCI and healthy controls (HC) as measured by electroencephalography (EEG) mean power spectra

  baseline data

• Differences in sleep quality between MCI and healthy controls (HC) as measured by sleep spindle count assessed from EEG

  baseline data

• Differences in sleep quality between MCI and healthy controls (HC) as measured by sleep spindle power assessed from EEG

  baseline data

• Differences in autophagy-related blood markers pre and post spermidine intervention in MCI as measured by eIF5A hypusination

  baseline, 2 weeks after baseline, 12-week follow-up

Study Arms (3)

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

Interventions

Spermidine Supplementation DIETARY_SUPPLEMENT

supplementation of 6 mg Spermidine per day across 3 doses

Dietary Supplement

Dietary Placebo DIETARY_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))

Dietary Placebo

Eligibility Criteria

• Age: 55 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women
• Written consent to participate in the study
• German at native speaker level
• Age between 55 and 70 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medicine Greifswald: lead
• Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald: collaborator
• Institute of Biology, Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin: collaborator
• Department of Experimental Neuroimmunology, University Medicine: collaborator

Study Sites (1)

Department of Neurology, University Medicine Greifswald

Greifswald, Mecklenburg-Vorpommern, 17475, Germany

RECRUITING

Related Publications (4)

• 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.

  PMID: 17086200 BACKGROUND

• Gupta 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.

  PMID: 27684064 BACKGROUND

• Minois 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.

  PMID: 21869457 BACKGROUND

• Madeo F, Eisenberg T, Pietrocola F, Kroemer G. Spermidine in health and disease. Science. 2018 Jan 26;359(6374):eaan2788. doi: 10.1126/science.aan2788.

  PMID: 29371440 BACKGROUND

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Agnes Flöel, Prof. Dr.

CONTACT

+49 (0)3834 86-6815; agnes.floeel@med.uni-greifswald.de

Silke M Wortha, Dr.

CONTACT

+49 3834 86 - 6704; SilkeMaria.Wortha@med.uni-greifswald.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med Agnes Flöel, Head of Department of Neurology

Study Record Dates

• First Submitted: September 17, 2025
• First Posted: February 3, 2026
• Study Start: October 28, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: February 3, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)