Subjective Cognitive DeclineNCT04744922
Clinical and Biological Effects of Citrus-phytochemicals in Subjective Cognitive Decline.
A study testing Extracts of citrus peels standardized in AUR and NAR (phytocomplex). in people with Subjective Cognitive Decline, run by IRCCS Centro San Giovanni di Dio Fatebenefratelli at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Subjective Cognitive Decline
- What is being tested?
- Extracts of citrus peels standardized in AUR and NAR (phytocomplex).
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteItaly
- Study dates
- 7 Apr 2021to 15 May 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 60 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- subjective cognitive decline,
- lack of objective cognitive impairment.
Who cannot join
- clinically significant depression and anxiety,
- psychiatric disorders,
- unstable medical conditions.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical and Biological Effects of Citrus-phytochemicals in Subjective Cognitive Decline: a Pilot Randomized Controlled Trial.
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.
Read the detailed description
Background: Alzheimer's disease (AD) is a neurodegenerative disorder which represents a major health issue and financial burden for health care systems around the world. The impact will further increase over the next decades due to increasing life expectancies. AD leads to progressive and irreversible disturbances of cognition and functional abilities. AD is the fifth-leading cause of death among those age 65 and older and is also a leading cause of disability and poor health. Due to the absence of a cure against AD, the public health priority has focused more recently on improvement of cognitive performance in older age and, possibly, prevention of cognitive decline. Subjective cognitive decline (SCD) in older adults is increasingly recognized as a potential indicator of non-normative cognitive decline and eventual progression to dementia. Longitudinal studies in SCD showed an up to 4.5-fold increased risk for progression to mild cognitive impairment. SCD has also been characterized by pathological changes of the brain associated with AD. These findings suggest that SCD may be an early clinical marker for AD, making an ideal target to test preventive interventions. Several nutraceuticals have displayed over the years the ability or potential to improve cognitive impairment. Among these, auraptene (AUR) and naringenin (NAR) are natural bioactive compounds derived from peels of Citrus fruits, with a strong preclinical rationale for cognitive enhancement. In fact, preclinical studies showed that they have anti-inflammatory, antioxidant, and neuroprotective effects in mouse brain and, specifically, in AD mouse models. These effects are mediated by a number of neuropeptides, growth factors, hormones, and cytokines, which are components of the neuroendocrine and immune (NEI) system, a complex network of communication, which showed altered functioning in ageing and neurodegenerative diseases.
The capacity of some nutraceutical in restoring and remodelling the NEI response at both neuroendocrine and immune level, could represent a new strategy in order to reach healthy ageing and prevent cognitive decline in the elderly. This perspective is supported by the results of a randomized, placebo-controlled, double blind study of 84 older adults, in which administration of AUR for 24 weeks showed significantly higher percentage of improvement in the immediate memory in the AUR group compared to the placebo.
Specific aims: This is a pilot randomized controlled trial to determine the cognitive and biological effects of Citrus peels extracts standardized in auraptene and naringenin, in individuals with SCD.
Specific aim 1. The investigators will enrol 80 individuals with SCD randomized into two groups of treatments, i.e. control and Citrus peels extracts. Cognitive assessment will be carried out at baseline and after 9 months of treatment, in order to evaluate the effect on cognition.
The investigators hypothesize that treatment group has an improvement in cognition compared to placebo group.
Specific aim 2. To evaluate the biological effects of the Citrus peels extracts treatment on the NEI system, through blood samples taken at baseline, and after 9 months of treatment.
The investigators hypothesize that treatment group has an improvement in the NEI functions as indicated by biological markers (increase of the growth factors, reduction of stress hormones levels, reduction of inflammation) compared to placebo group.
- Conditions
- Subjective Cognitive Decline
- Being tested
- Extracts of citrus peels standardized in AUR and NAR (phytocomplex).
- Keywords
- Citrus-phytochemicals, auraptene, naringenin, subjective cognitive decline, randomized, efficacy, cognitive tests, R-BANS, interleukins, Interleukin-8
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extracts of citrus peels standardized in AUR and NAR (phytocomplex).Dietary supplement
One capsule a day for 9 months
| Study group | Role | What they receive |
|---|---|---|
| Auraptene and Naringenin Arm | Experimental | One capsule a day for 9 months Receives: Dietary Supplement: Extracts of citrus peels standardized in AUR and NAR (phytocomplex). |
| Control Arm | Placebo comparator | One capsule a day for 9 months Receives: Dietary Supplement: Extracts of citrus peels standardized in AUR and NAR (phytocomplex). |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 9 months
Secondary outcomes (1)
Biological outcome
Interleukin-8
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2021
- Study start7 Apr 2021
- Primary completion15 May 2023
- Study completion15 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Subjective Cognitive DeclineStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS Centro San Giovanni di Dio Fatebenefratelli
- Sponsor type
- University, hospital or other
- Collaborators
- University of Chieti
- Responsible party
- Sponsor
- Investigators
- Samantha Galluzzi, Principal investigator, IRCCS Centro San Giovanni di Dio Fatebenefratelli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04744922
- Sponsor's protocol ID
- 270/2020
- Status last verified
- Mar 2023
- First submitted
- 5 Feb 2021
- Last updated
- 18 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data collected in this study will not be publicly available but will be provided to any qualified researcher interested in the topic of this project, upon presentation of a research study and approval of the local Ethics Committee.
Publications
Rebello CJ, Beyl RA, Lertora JJL, Greenway FL, Ravussin E, Ribnicky DM, Poulev A, Kennedy BJ, Castro HF, Campagna SR, Coulter AA, Redman LM. Safety and pharmacokinetics of naringenin: A randomized, controlled, single-ascending-dose clinical trial. Diabetes Obes Metab. 2020 Jan;22(1):91-98. doi: 10.1111/dom.13868. Epub 2019 Sep 30.
PubMed 31468636Jessen F, Amariglio RE, van Boxtel M, Breteler M, Ceccaldi M, Chetelat G, Dubois B, Dufouil C, Ellis KA, van der Flier WM, Glodzik L, van Harten AC, de Leon MJ, McHugh P, Mielke MM, Molinuevo JL, Mosconi L, Osorio RS, Perrotin A, Petersen RC, Rabin LA, Rami L, Reisberg B, Rentz DM, Sachdev PS, de la Sayette V, Saykin AJ, Scheltens P, Shulman MB, Slavin MJ, Sperling RA, Stewart R, Uspenskaya O, Vellas B, Visser PJ, Wagner M; Subjective Cognitive Decline Initiative (SCD-I) Working Group. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease. Alzheimers Dement. 2014 Nov;10(6):844-52. doi: 10.1016/j.jalz.2014.01.001. Epub 2014 May 3.
PubMed 24798886Rabin LA, Smart CM, Crane PK, Amariglio RE, Berman LM, Boada M, Buckley RF, Chetelat G, Dubois B, Ellis KA, Gifford KA, Jefferson AL, Jessen F, Katz MJ, Lipton RB, Luck T, Maruff P, Mielke MM, Molinuevo JL, Naeem F, Perrotin A, Petersen RC, Rami L, Reisberg B, Rentz DM, Riedel-Heller SG, Risacher SL, Rodriguez O, Sachdev PS, Saykin AJ, Slavin MJ, Snitz BE, Sperling RA, Tandetnik C, van der Flier WM, Wagner M, Wolfsgruber S, Sikkes SA. Subjective Cognitive Decline in Older Adults: An Overview of Self-Report Measures Used Across 19 International Research Studies. J Alzheimers Dis. 2015 Sep 24;48 Suppl 1(0 1):S63-86. doi: 10.3233/JAD-150154.
PubMed 26402085Reisberg B, Shulman MB, Torossian C, Leng L, Zhu W. Outcome over seven years of healthy adults with and without subjective cognitive impairment. Alzheimers Dement. 2010 Jan;6(1):11-24. doi: 10.1016/j.jalz.2009.10.002.
PubMed 20129317Amariglio 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.
PubMed 26048028Mecocci P, Tinarelli C, Schulz RJ, Polidori MC. Nutraceuticals in cognitive impairment and Alzheimer's disease. Front Pharmacol. 2014 Jun 23;5:147. doi: 10.3389/fphar.2014.00147. eCollection 2014.
PubMed 25002849Okuyama 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.
PubMed 26569206Okuyama 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.
PubMed 31061292Ghofrani 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.
PubMed 26148826Okuyama 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.
PubMed 29424280Sanchez-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.
PubMed 30845690ThyagaRajan 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.
PubMed 25205962Rolandi 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.
PubMed 40366507Galluzzi 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.
PubMed 39482712Galluzzi 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.
PubMed 36253765
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical and Biological Effects of Citrus-phytochemicals in Subjective Cognitive Decline: a Pilot Randomized Controlled Trial.
- ClinicalTrials.gov ID
- NCT04744922
- Acronym / sponsor ID
- 270/2020
- Conditions
- Subjective Cognitive Decline
- Keywords
- Citrus-phytochemicals, auraptene, naringenin, subjective cognitive decline, randomized, efficacy, cognitive tests, R-BANS, interleukins, Interleukin-8
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- IRCCS Centro San Giovanni di Dio FatebenefratelliUniversity, hospital or other
- Collaborators
- University of Chieti
- Study start
- 7 Apr 2021 (actual)
- Primary completion
- 15 May 2023 (actual)
- Study completion
- 15 May 2023 (actual)
- First posted
- 9 Feb 2021 (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.
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.
Detailed description
Background: Alzheimer's disease (AD) is a neurodegenerative disorder which represents a major health issue and financial burden for health care systems around the world. The impact will further increase over the next decades due to increasing life expectancies. AD leads to progressive and irreversible disturbances of cognition and functional abilities. AD is the fifth-leading cause of death among those age 65 and older and is also a leading cause of disability and poor health. Due to the absence of a cure against AD, the public health priority has focused more recently on improvement of cognitive performance in older age and, possibly, prevention of cognitive decline. Subjective cognitive decline (SCD) in older adults is increasingly recognized as a potential indicator of non-normative cognitive decline and eventual progression to dementia. Longitudinal studies in SCD showed an up to 4.5-fold increased risk for progression to mild cognitive impairment. SCD has also been characterized by pathological changes of the brain associated with AD. These findings suggest that SCD may be an early clinical marker for AD, making an ideal target to test preventive interventions. Several nutraceuticals have displayed over the years the ability or potential to improve cognitive impairment. Among these, auraptene (AUR) and naringenin (NAR) are natural bioactive compounds derived from peels of Citrus fruits, with a strong preclinical rationale for cognitive enhancement. In fact, preclinical studies showed that they have anti-inflammatory, antioxidant, and neuroprotective effects in mouse brain and, specifically, in AD mouse models. These effects are mediated by a number of neuropeptides, growth factors, hormones, and cytokines, which are components of the neuroendocrine and immune (NEI) system, a complex network of communication, which showed altered functioning in ageing and neurodegenerative diseases.
The capacity of some nutraceutical in restoring and remodelling the NEI response at both neuroendocrine and immune level, could represent a new strategy in order to reach healthy ageing and prevent cognitive decline in the elderly. This perspective is supported by the results of a randomized, placebo-controlled, double blind study of 84 older adults, in which administration of AUR for 24 weeks showed significantly higher percentage of improvement in the immediate memory in the AUR group compared to the placebo.
Specific aims: This is a pilot randomized controlled trial to determine the cognitive and biological effects of Citrus peels extracts standardized in auraptene and naringenin, in individuals with SCD.
Specific aim 1. The investigators will enrol 80 individuals with SCD randomized into two groups of treatments, i.e. control and Citrus peels extracts. Cognitive assessment will be carried out at baseline and after 9 months of treatment, in order to evaluate the effect on cognition.
The investigators hypothesize that treatment group has an improvement in cognition compared to placebo group.
Specific aim 2. To evaluate the biological effects of the Citrus peels extracts treatment on the NEI system, through blood samples taken at baseline, and after 9 months of treatment.
The investigators hypothesize that treatment group has an improvement in the NEI functions as indicated by biological markers (increase of the growth factors, reduction of stress hormones levels, reduction of inflammation) compared to placebo group.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Auraptene and Naringenin Arm | Experimental | Dietary Supplement: Extracts of citrus peels standardized in AUR and NAR (phytocomplex).One capsule a day for 9 months |
| Control Arm | Placebo comparator | Dietary Supplement: Extracts of citrus peels standardized in AUR and NAR (phytocomplex).One capsule a day for 9 months |
Who may qualify
- Ages
- 60 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- subjective cognitive decline,
- lack of objective cognitive impairment.
Key exclusion criteria (3 listed)
- clinically significant depression and anxiety,
- psychiatric disorders,
- unstable medical conditions.
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 |
|---|---|---|
| Extracts of citrus peels standardized in AUR and NAR (phytocomplex).One capsule a day for 9 months | Dietary supplement | Auraptene and Naringenin Arm, Control Arm |
Primary outcome
Cognitive outcome
Time frame: 9 months
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.
1 secondary outcome
Biological outcome
Time frame: 9 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2023.
- Background: PubMed 31468636Rebello CJ, Beyl RA, Lertora JJL, Greenway FL, Ravussin E, Ribnicky DM, Poulev A, Kennedy BJ, Castro HF, Campagna SR, Coulter AA, Redman LM. Safety and pharmacokinetics of naringenin: A randomized, controlled, single-ascending-dose clinical trial. Diabetes Obes Metab. 2020 Jan;22(1):91-98. doi: 10.1111/dom.13868. Epub 2019 Sep 30.
- Background: PubMed 24798886Jessen F, Amariglio RE, van Boxtel M, Breteler M, Ceccaldi M, Chetelat G, Dubois B, Dufouil C, Ellis KA, van der Flier WM, Glodzik L, van Harten AC, de Leon MJ, McHugh P, Mielke MM, Molinuevo JL, Mosconi L, Osorio RS, Perrotin A, Petersen RC, Rabin LA, Rami L, Reisberg B, Rentz DM, Sachdev PS, de la Sayette V, Saykin AJ, Scheltens P, Shulman MB, Slavin MJ, Sperling RA, Stewart R, Uspenskaya O, Vellas B, Visser PJ, Wagner M; Subjective Cognitive Decline Initiative (SCD-I) Working Group. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease. Alzheimers Dement. 2014 Nov;10(6):844-52. doi: 10.1016/j.jalz.2014.01.001. Epub 2014 May 3.
- Background: PubMed 26402085Rabin LA, Smart CM, Crane PK, Amariglio RE, Berman LM, Boada M, Buckley RF, Chetelat G, Dubois B, Ellis KA, Gifford KA, Jefferson AL, Jessen F, Katz MJ, Lipton RB, Luck T, Maruff P, Mielke MM, Molinuevo JL, Naeem F, Perrotin A, Petersen RC, Rami L, Reisberg B, Rentz DM, Riedel-Heller SG, Risacher SL, Rodriguez O, Sachdev PS, Saykin AJ, Slavin MJ, Snitz BE, Sperling RA, Tandetnik C, van der Flier WM, Wagner M, Wolfsgruber S, Sikkes SA. Subjective Cognitive Decline in Older Adults: An Overview of Self-Report Measures Used Across 19 International Research Studies. J Alzheimers Dis. 2015 Sep 24;48 Suppl 1(0 1):S63-86. doi: 10.3233/JAD-150154.
- Background: PubMed 20129317Reisberg B, Shulman MB, Torossian C, Leng L, Zhu W. Outcome over seven years of healthy adults with and without subjective cognitive impairment. Alzheimers Dement. 2010 Jan;6(1):11-24. doi: 10.1016/j.jalz.2009.10.002.
- Background: PubMed 26048028Amariglio 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.
- Background: PubMed 25002849Mecocci P, Tinarelli C, Schulz RJ, Polidori MC. Nutraceuticals in cognitive impairment and Alzheimer's disease. Front Pharmacol. 2014 Jun 23;5:147. doi: 10.3389/fphar.2014.00147. eCollection 2014.
- Background: PubMed 26569206Okuyama 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.
- Background: PubMed 31061292Okuyama 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.
- Background: PubMed 26148826Ghofrani 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.
- Background: PubMed 29424280Okuyama 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.
- Background: PubMed 30845690Sanchez-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.
- Background: PubMed 25205962ThyagaRajan 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The data collected in this study will not be publicly available but will be provided to any qualified researcher interested in the topic of this project, upon presentation of a research study and approval of the local Ethics Committee.
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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. This study is not recruiting at the moment.
Samantha Galluzzi principal investigator
IRCCS Centro San Giovanni di Dio Fatebenefratelli
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Extracts of citrus peels standardized in AUR and NAR (phytocomplex). in people with Subjective Cognitive Decline, run by IRCCS Centro San Giovanni di Dio Fatebenefratelli at 1 site in Italy.
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 2 inclusion and 3 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: finished, as of the sponsor's last update on 18 Jun 2023. 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 Italy. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive outcome (time frame: 9 months). 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 NCT04744922, which also lists 15 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 18 Jun 2023.