An Exploratory Clinical Study on Autophagy and Multi-level Molecular Profiling During Spermidine Supplementation

NCT04823806 | Unknown

• 1 other identifier: StressLess
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Recently, the autophagy inducing caloric restriction mimic spermidine became available. Autophagy is essential for energy and cellular homeostasis through protein catabolism and dysregulation results in compromised proteostasis, stress-coping behavior, and in excessive secretion of signaling molecules and inflammatory cytokines. Antidepressants for example effect autophagy dependent pathways to exert their beneficial effects. It can therefore be hypothesized that autophagy induction through spermidine supplementation also shows beneficial clinical effect, particularly in the field of psychiatric conditions. It would be safe, low cost and easy to implement in relay to psychotropic medication in the treatment of psychiatric patients.Therefore, the aim of the project is to analyze clinical effects of spermidine supplementation in correlation to the underlying, multi-level molecular profiling.

Conditions

Depression; Healthy

Keywords

Spermidine; Autophagy; Depression

Outcome Measures

Primary Outcomes (1)

• Proteomics and autophagy processes

  Change in protein levels of autophagy biomarkers (LC3II \& p62) of isolated PBMCs (peripheral blood mononuclear cells) by Western Blotting.

  change from baseline over 21 days of supplementation to 7 day follow up

Secondary Outcomes (25)

• Epigenetic patterns

  change from baseline to day 21 of supplementation to 7 day follow up

• Proteome/phosphoproteome/ubiquitinome patterns

  change from baseline over 21 days of supplementation to 7 day follow up

• Metabolic processes

  change from baseline over 21 days of supplementation to 7 day follow up

• Lipid profiling

  change from baseline over 21 days of supplementation to 7 day follow up

• Exosomal protein patterns

  change from baseline over 21 days of supplementation to 7 day follow up

Study Arms (2)

Healthy participants and participants with depressive disorder: dietary spermidine supplementation

EXPERIMENTAL

Dietary Supplement: Polyamine 21 days of spermidine supplementation (3 sachets/day = 6mg spermidine/day)

Dietary Supplement: Spermidine (spermidineLIFE ®) OR Placebo

Healthy participants and participants with depressive disorder: dietary placebo supplementation

PLACEBO COMPARATOR

Dietary Supplement: Placebo 21 days of Placebo supplementation (3 sachets/day)

Dietary Supplement: Spermidine (spermidineLIFE ®) OR Placebo

Interventions

Spermidine (spermidineLIFE ®) OR Placebo DIETARY_SUPPLEMENT

21 day of 6mg spermidine OR Placebo supplementation per day

Healthy participants and participants with depressive disorder: dietary placebo supplementation; Healthy participants and participants with depressive disorder: dietary spermidine supplementation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Present written declaration of consent
• Healty or diagnosed with depression
• BMI between 17 and 40

You may not qualify if:

• Insufficient linguistic communication
• Pregnancy or lactation
• Gluten, histamine or wheat seedling intolerance
• Drug abuse or alcohol dependency
• Current spermidine substitution

Sponsors & Collaborators

• University Hospital, Bonn: lead

Study Sites (1)

University Hospital Bonn, Clinic for psychiatry and psychotherapy

Bonn, 53111, Germany

Location

Related Publications (5)

• Eisenberg T, Knauer H, Schauer A, Buttner S, Ruckenstuhl C, Carmona-Gutierrez D, Ring J, Schroeder S, Magnes C, Antonacci L, Fussi H, Deszcz L, Hartl R, Schraml E, Criollo A, Megalou E, Weiskopf D, Laun P, Heeren G, Breitenbach M, Grubeck-Loebenstein B, Herker E, Fahrenkrog B, Frohlich KU, Sinner F, Tavernarakis N, Minois N, Kroemer G, Madeo F. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 2009 Nov;11(11):1305-14. doi: 10.1038/ncb1975. Epub 2009 Oct 4.

  PMID: 19801973 RESULT

• 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 RESULT

• Fond G, Macgregor A, Leboyer M, Michalsen A. Fasting in mood disorders: neurobiology and effectiveness. A review of the literature. Psychiatry Res. 2013 Oct 30;209(3):253-8. doi: 10.1016/j.psychres.2012.12.018. Epub 2013 Jan 15.

  PMID: 23332541 RESULT

• Galluzzi L, Bravo-San Pedro JM, Levine B, Green DR, Kroemer G. Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat Rev Drug Discov. 2017 Jul;16(7):487-511. doi: 10.1038/nrd.2017.22. Epub 2017 May 19.

  PMID: 28529316 RESULT

• Jia J, Le W. Molecular network of neuronal autophagy in the pathophysiology and treatment of depression. Neurosci Bull. 2015 Aug;31(4):427-34. doi: 10.1007/s12264-015-1548-2. Epub 2015 Aug 8.

  PMID: 26254058 RESULT

MeSH Terms

Conditions

Depression

Interventions

Spermidine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Putrescine; Biogenic Polyamines; Biogenic Amines; Amines; Organic Chemicals; Polyamines

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double-blind study (participants nor experimenters know who receives placebo or spermidine supplementation)
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. rer. nat. Nils Gassen

Model Details: 2 groups of different inclusion criteria (healthy or depressive disorder) each group undergoing one out of two conditions (spermidine vs. placebo Supplementation) (randomized)

Study Record Dates

• First Submitted: March 24, 2021
• First Posted: April 1, 2021
• Study Start: December 1, 2020
• Primary Completion: June 1, 2022
• Study Completion: December 1, 2024
• Last Updated: November 10, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)