Evaluation of Essential Metal Metabolism

NCT06911515 | Active Not Recruiting

• 1 other identifier: 6279
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Disturbance of Consciousness; Alteration of Metabolism; Essential Metals

Keywords

patients with disturbance of consciousness; essential metal; metabolism status

Outcome Measures

Primary Outcomes (1)

• Blood concetration of essential metal in patients with acquired brain injury

  Quantification of blood essential metal levels in peripheral venous blood samples in patients with acquired brain injury (Fe, range: Men: 65-178 µg/dL, Women: 50-170 µg/dL; Zn, range: 75- 110 µg/dL; Cu, range: Men: 60-160 µg/dL, Women: 80-155 µg/dL;non-Cp Cu, range: less than 5 µg/dL) compared to healthy patients.

  Changes from baseline (T0), after 30 days of treatment (T1)

Secondary Outcomes (5)

• Differences in essential metal blood concentration in subcategories of patients with impaired consciousness

  At baseline (T0) and 30 days (T1)

• Differences in essential metal blood concentration in subcategories of patients with acquired brain injury (traumatic vs non-traumatic)

  At baseline (T0) and 30 days (T1)

• Correlation between clinical outcome related to autonomy and disability and essential metal blood concentration

  At baseline (T0) and 30 days (T1)

• Correlation between clinical outcome related to motor performance and essential metal blood concentration

  At baseline (T0) and 30 days (T1)

• Correlation between clinical outcome related to state of consciousness and cognitive level and essential metal blood concentration

  At baseline (T0) and 30 days (T1)

Study Arms (2)

Experimental: Gruop A

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

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

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

Interventions

peripheral venous blood samples, these will be performed in order to measure the biological markers in the serum 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; Experimental: Gruop A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients of both sexes with DoC being treated at the U.O.C. of High Intensity Neurorehabilitation, Fondazione Policlinico Universitario Gemelli IRCCS of Rome

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

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

Roma, RM, 00168, Italy

Location

Related Publications (11)

• 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.

  PMID: 36040154 BACKGROUND

• 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.

  PMID: 35892326 BACKGROUND

• 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.

  PMID: 16350959 BACKGROUND

• 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.

  PMID: 34209820 BACKGROUND

• 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.

  PMID: 34219710 BACKGROUND

• 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.

  PMID: 30333789 BACKGROUND

• 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.

  PMID: 37047843 BACKGROUND

• 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.

  PMID: 25292271 BACKGROUND

• 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.

  PMID: 22574081 BACKGROUND

• 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.

  PMID: 21040571 BACKGROUND

• 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.

  PMID: 25335757 BACKGROUND

Study Officials

• Stefano mr Bonomi, MD,

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: associated professor

Study Record Dates

• First Submitted: March 17, 2025
• First Posted: April 4, 2025
• Study Start: March 17, 2025
• Primary Completion: March 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: April 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)