Evaluation of Essential Metal Metabolism

NCT ID: NCT06911515

Last Updated: 2025-04-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

120 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-03-17

Study Completion Date

2027-03-31

Brief Summary

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Disturbance of consciousness (DoC) is a state in which consciousness is altered following brain damage and can manifest in several conditions that result from the loss of regulation of the neural function of the two components of consciousness, alertness and awareness.

It is known that the main causes of disorders of consciousness have important effects on the disruption of essential metal homeostasis.

In particular, myocardial infarction and heart failure, ischemic and hemorrhagic stroke and head trauma trigger phenomena of diffuse axonal damage, hypoxia and re-perfusion that profoundly alter the metabolism of cerebral O2 that reacts with essential metals , in Fenton-type reactions whose predominant effect is an extensive production of reactive oxygen species (ROS) and pro-oxidant molecules.

Fe, Cu and zinc (Zn) are essential metals for life: two thirds of the proteins in our body use these metals that play a crucial role as catalysts or structural elements of proteins in various biological processes, such as cellular respiration in mitochondria, the production and maturation of red and white blood cells, the elasticity of connective tissue, the production of myelin and the production of some neurotransmitters. For this reason, the biology of essential metals has a major impact on our health and the disruption of their homeostasis inexorably leads to disease.

These metals are very important for the metabolism of the Central Nervous System (CNS) and Cu, in particular, even in adults, is involved in the production of myelin and in the production of some neurotransmitters of the diffuse modulatory systems . Cu is a cofactor of the enzymes dopamine β-hydroxylase, and monoamine oxidase involved in the balance of catecholamines , and is altered in some disorders of Cu metabolism.

Detailed Description

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Conditions

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Disturbance of Consciousness Alteration of Metabolism Essential Metals

Study Design

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Observational Model Type

OTHER

Study Time Perspective

OTHER

Study Groups

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Experimental: Gruop A

Difference in metal concentrations (7 metals) in GCA subjects compared to those in previously acquired sera of healthy controls.

peripheral venous blood samples, these will be performed in order to measure the biological markers in the serum

Intervention Type OTHER

peripheral venous blood samples, these will be performed in order to measure the biological markers in the serum

Experimental: Group B: Differences and Correlation

Differences in essential metal concentrations at 30 days compared to baseline in GCA patients.

* Baseline differences in essential metal metabolism in subcategories of patients with impaired consciousness (coma/VS vs MCS, traumatic brain injury vs non-traumatic brain injury).
* Correlation between clinical scales and essential metal metabolism

peripheral venous blood samples, these will be performed in order to measure the biological markers in the serum

Intervention Type OTHER

peripheral venous blood samples, these will be performed in order to measure the biological markers in the serum

Interventions

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peripheral venous blood samples, these will be performed in order to measure the biological markers in the serum

peripheral venous blood samples, these will be performed in order to measure the biological markers in the serum

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Patients who have been in a coma state, documented with a GCS ≤ 8 for at least 24 hours;

* Presence of a disturbance of consciousness, identified through the Coma Recovery Scale-revised (CRS-r) and classified as coma, vegetative state or minimally conscious state;
* Latency of the acute event between 15 days and 6 months;
* Ability of the caregiver/guardian to understand and sign the informed consent.

Exclusion Criteria

* Age \<18 years;

* Psychiatric or other pathologies;
* Inflammatory state related to ongoing infections;
* Refusal or inability to sign the written informed consent to participate in the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role lead

Responsible Party

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PADUA LUCA

associated professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Stefano mr Bonomi, MD,

Role: STUDY_CHAIR

Fondazione Policlinico Universitario A. Gemelli, IRCCS

Locations

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UOC Neuroriabilitazione ad alta intensità , Policlinico "A. Gemelli"

Roma, RM, Italy

Site Status

Countries

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Italy

References

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Grassi M, Palluzzi F, Tarantino B. SEMgraph: an R package for causal network inference of high-throughput data with structural equation models. Bioinformatics. 2022 Oct 14;38(20):4829-4830. doi: 10.1093/bioinformatics/btac567.

Reference Type BACKGROUND
PMID: 36040154 (View on PubMed)

Nicoletti VG, Pajer K, Calcagno D, Pajenda G, Nogradi A. The Role of Metals in the Neuroregenerative Action of BDNF, GDNF, NGF and Other Neurotrophic Factors. Biomolecules. 2022 Jul 22;12(8):1015. doi: 10.3390/biom12081015.

Reference Type BACKGROUND
PMID: 35892326 (View on PubMed)

Giacino JT, Kalmar K. Diagnostic and prognostic guidelines for the vegetative and minimally conscious states. Neuropsychol Rehabil. 2005 Jul-Sep;15(3-4):166-74. doi: 10.1080/09602010443000498.

Reference Type BACKGROUND
PMID: 16350959 (View on PubMed)

Squitti R, Ventriglia M, Simonelli I, Bonvicini C, Costa A, Perini G, Binetti G, Benussi L, Ghidoni R, Koch G, Borroni B, Albanese A, Sensi SL, Rongioletti M. Copper Imbalance in Alzheimer's Disease: Meta-Analysis of Serum, Plasma, and Brain Specimens, and Replication Study Evaluating ATP7B Gene Variants. Biomolecules. 2021 Jun 29;11(7):960. doi: 10.3390/biom11070960.

Reference Type BACKGROUND
PMID: 34209820 (View on PubMed)

Squitti R, Faller P, Hureau C, Granzotto A, White AR, Kepp KP. Copper Imbalance in Alzheimer's Disease and Its Link with the Amyloid Hypothesis: Towards a Combined Clinical, Chemical, and Genetic Etiology. J Alzheimers Dis. 2021;83(1):23-41. doi: 10.3233/JAD-201556.

Reference Type BACKGROUND
PMID: 34219710 (View on PubMed)

Cheng L, Cortese D, Monti MM, Wang F, Riganello F, Arcuri F, Di H, Schnakers C. Do Sensory Stimulation Programs Have an Impact on Consciousness Recovery? Front Neurol. 2018 Oct 2;9:826. doi: 10.3389/fneur.2018.00826. eCollection 2018.

Reference Type BACKGROUND
PMID: 30333789 (View on PubMed)

Squitti R, Reale G, Tondolo V, Crescenti D, Bellini S, Moci M, Caliandro P, Padua L, Rongioletti M. Imbalance of Essential Metals in Traumatic Brain Injury and Its Possible Link with Disorders of Consciousness. Int J Mol Sci. 2023 Apr 6;24(7):6867. doi: 10.3390/ijms24076867.

Reference Type BACKGROUND
PMID: 37047843 (View on PubMed)

Dolce G, Lucca LF, Riganello F, Arcuri F, Quintieri M, Cortese MD, Pignolo L. Advances in the neurorehabilitation of severe disorder of consciousness. Ann Ist Super Sanita. 2014;50(3):234-40. doi: 10.4415/ANN_14_03_06.

Reference Type BACKGROUND
PMID: 25292271 (View on PubMed)

von Wild K, Laureys ST, Gerstenbrand F, Dolce G, Onose G. The vegetative state--a syndrome in search of a name. J Med Life. 2012 Feb 22;5(1):3-15. Epub 2012 Mar 5.

Reference Type BACKGROUND
PMID: 22574081 (View on PubMed)

Laureys S, Celesia GG, Cohadon F, Lavrijsen J, Leon-Carrion J, Sannita WG, Sazbon L, Schmutzhard E, von Wild KR, Zeman A, Dolce G; European Task Force on Disorders of Consciousness. Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome. BMC Med. 2010 Nov 1;8:68. doi: 10.1186/1741-7015-8-68.

Reference Type BACKGROUND
PMID: 21040571 (View on PubMed)

Davis T, Ings A; National Institute of Health and Care Excellence. Head injury: triage, assessment, investigation and early management of head injury in children, young people and adults (NICE guideline CG 176). Arch Dis Child Educ Pract Ed. 2015 Apr;100(2):97-100. doi: 10.1136/archdischild-2014-306797. Epub 2014 Oct 21. No abstract available.

Reference Type BACKGROUND
PMID: 25335757 (View on PubMed)

Other Identifiers

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6279

Identifier Type: -

Identifier Source: org_study_id

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