Clinical and Biological Effects of Citrus-phytochemicals in Subjective Cognitive Decline.

NCT04744922 | Completed

• 1 other identifier: 270/2020
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Subjective cognitive decline (SCD) is receiving increasing attention as a risk factor for incident dementia due to AD. SCD manifests prior to the onset of clinical impairment, and as such could serve as a potential target population for early intervention trials. The pathogenesis of AD is complex and involves a dysregulation of the neuroendocrine immune (NEI) system, a network of signaling molecules, such as neurotransmitters, hormones and cytokines. As a result, it may be unlikely that cognitive decline may be mitigated by drugs acting on a single specific target. Plant extracts acting at different levels of the NEI regulation could represent appealing therapeutic strategies for cognitive decline. Citrus-derived phytochemicals, like auraptene and naringenin, showed antioxidant, anti-inflammatory, and neuroprotective effects in preclinical studies of AD mouse models and preservation of cognition in elderly without cognitive impairment. This is a pilot randomized controlled trial to determine clinical and biological effects of Citrus-phytochemicals in individuals with SCD. Participants will be randomized to receive Citrus-phytochemicals standardized in auraptene and naringenin or placebo for 9 months. Cognitive tests and blood-based biological markers will be done at baseline and at the end of treatment as outcome measures.

Conditions

Subjective Cognitive Decline

Keywords

Citrus-phytochemicals, auraptene, naringenin; subjective cognitive decline, randomized, efficacy; cognitive tests, R-BANS, interleukins, Interleukin-8

Outcome Measures

Primary Outcomes (1)

• Cognitive outcome

  Repeatable Battery for the Assessment of the Neuropsychological Status (R-BANS). The minimum score is 40 and the maximum is 160. Higher scores mean a better performances.

  9 months

Secondary Outcomes (1)

• Biological outcome

  9 months

Study Arms (2)

Auraptene and Naringenin Arm

EXPERIMENTAL

One capsule a day for 9 months

Dietary Supplement: Extracts of citrus peels standardized in AUR and NAR (phytocomplex).

Control Arm

PLACEBO COMPARATOR

One capsule a day for 9 months

Dietary Supplement: Extracts of citrus peels standardized in AUR and NAR (phytocomplex).

Interventions

Extracts of citrus peels standardized in AUR and NAR (phytocomplex). DIETARY_SUPPLEMENT

One capsule a day for 9 months

Auraptene and Naringenin Arm; Control Arm

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• subjective cognitive decline,
• lack of objective cognitive impairment.

You may not qualify if:

• clinically significant depression and anxiety,
• psychiatric disorders,
• unstable medical conditions.

Sponsors & Collaborators

• IRCCS Centro San Giovanni di Dio Fatebenefratelli: lead
• University of Chieti: collaborator

Study Sites (1)

IRCCS Centro San Giovanni di Dio Fatebenefratelli

Brescia, 25125, Italy

Location

Related Publications (15)

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  PMID: 31468636 BACKGROUND

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  PMID: 24798886 BACKGROUND

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  PMID: 20129317 BACKGROUND

• Amariglio RE, Mormino EC, Pietras AC, Marshall GA, Vannini P, Johnson KA, Sperling RA, Rentz DM. Subjective cognitive concerns, amyloid-beta, and neurodegeneration in clinically normal elderly. Neurology. 2015 Jul 7;85(1):56-62. doi: 10.1212/WNL.0000000000001712. Epub 2015 Jun 5.

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  PMID: 25002849 BACKGROUND

• Okuyama S, Morita M, Kaji M, Amakura Y, Yoshimura M, Shimamoto K, Ookido Y, Nakajima M, Furukawa Y. Auraptene Acts as an Anti-Inflammatory Agent in the Mouse Brain. Molecules. 2015 Nov 10;20(11):20230-9. doi: 10.3390/molecules201119691.

  PMID: 26569206 BACKGROUND

• Okuyama S, Kanzaki T, Kotani Y, Katoh M, Sawamoto A, Nakajima M, Furukawa Y. Continual Treatment with the Peels of Citrus kawachiensis (Kawachi Bankan) Protects against Dopaminergic Neuronal Cell Death in a Lipopolysaccharide-Induced Model of Parkinson's Disease. J Nutr Sci Vitaminol (Tokyo). 2019;65(2):205-208. doi: 10.3177/jnsv.65.205.

  PMID: 31061292 BACKGROUND

• Ghofrani S, Joghataei MT, Mohseni S, Baluchnejadmojarad T, Bagheri M, Khamse S, Roghani M. Naringenin improves learning and memory in an Alzheimer's disease rat model: Insights into the underlying mechanisms. Eur J Pharmacol. 2015 Oct 5;764:195-201. doi: 10.1016/j.ejphar.2015.07.001. Epub 2015 Jul 3.

  PMID: 26148826 BACKGROUND

• Okuyama S, Kotani Y, Yamamoto K, Sawamoto A, Sugawara K, Sudo M, Ohkubo Y, Tamanaha A, Nakajima M, Furukawa Y. The peel of Citrus kawachiensis (kawachi bankan) ameliorates microglial activation, tau hyper-phosphorylation, and suppression of neurogenesis in the hippocampus of senescence-accelerated mice. Biosci Biotechnol Biochem. 2018 May;82(5):869-878. doi: 10.1080/09168451.2018.1433993. Epub 2018 Feb 9.

  PMID: 29424280 BACKGROUND

• Sanchez-Rodriguez E, Biel-Glesson S, Fernandez-Navarro JR, Calleja MA, Espejo-Calvo JA, Gil-Extremera B, de la Torre R, Fito M, Covas MI, Vilchez P, Alche JD, Martinez de Victoria E, Gil A, Mesa MD. Effects of Virgin Olive Oils Differing in Their Bioactive Compound Contents on Biomarkers of Oxidative Stress and Inflammation in Healthy Adults: A Randomized Double-Blind Controlled Trial. Nutrients. 2019 Mar 6;11(3):561. doi: 10.3390/nu11030561.

  PMID: 30845690 BACKGROUND

• ThyagaRajan S, Priyanka HP. Bidirectional communication between the neuroendocrine system and the immune system: relevance to health and diseases. Ann Neurosci. 2012 Jan;19(1):40-6. doi: 10.5214/ans.0972.7531.180410.

  PMID: 25205962 BACKGROUND

• Rolandi E, Dodich A, Mandelli S, Canessa N, Ferrari C, Ribaldi F, Munaretto G, Ambrosi C, Gasparotti R, Violi D, Iannaccone S, Marcone A, Falini A, Frisoni GB, Galluzzi S, Cerami C, Cavedo E. Targeting brain health in subjective cognitive decline: insights from a multidomain randomized controlled trial. Aging Clin Exp Res. 2025 May 14;37(1):151. doi: 10.1007/s40520-025-03062-z.

  PMID: 40366507 DERIVED

• Galluzzi S, Marizzoni M, Gatti E, Bonfiglio NS, Cattaneo A, Epifano F, Frisoni GB, Genovese S, Geviti A, Marchetti L, Sgro G, Solorzano CS, Pievani M, Fiorito S. Citrus supplementation in subjective cognitive decline: results of a 36-week, randomized, placebo-controlled trial. Nutr J. 2024 Nov 1;23(1):135. doi: 10.1186/s12937-024-01039-8.

  PMID: 39482712 DERIVED

• Galluzzi S, Zanardini R, Ferrari C, Gipponi S, Passeggia I, Rampini M, Sgro G, Genovese S, Fiorito S, Palumbo L, Pievani M, Frisoni GB, Epifano F. Cognitive and biological effects of citrus phytochemicals in subjective cognitive decline: a 36-week, randomized, placebo-controlled trial. Nutr J. 2022 Oct 17;21(1):64. doi: 10.1186/s12937-022-00817-6.

  PMID: 36253765 DERIVED

Related Links

• Related Info

Study Officials

• Samantha Galluzzi

  IRCCS Centro San Giovanni di Dio Fatebenefratelli

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2021
• First Posted: February 9, 2021
• Study Start: April 7, 2021
• Primary Completion: May 15, 2023
• Study Completion: May 15, 2023
• Last Updated: June 18, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Access Criteria: Local Ethics Committee approval.

Locations

IT (1)