Evaluation of Essential Metal Metabolism

Active, not recruiting

• Conditions: Disturbance of Consciousness; Alteration of Metabolism; Essential Metals

• Registration Number: NCT06911515
• Lead Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2025-03-17
• Study First Submitted: 2025-03-17
• Study First Submitted QC: 2025-03-28
• Status Verified: 2025-04
• Study First Posted: 2025-04-04
• Last Update Submitted: 2025-04-08
• Last Update Posted: 2025-04-09
• Primary Completion: 2026-03-31
• Study Completion: 2027-03-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 120

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Blood concetration of essential metal in patients with acquired brain injury	Changes from baseline (T0), after 30 days of treatment (T1)	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.

Secondary Outcome Measures

Name	Time	Method
Differences in essential metal blood concentration in subcategories of patients with impaired consciousness	At baseline (T0) and 30 days (T1)	Baseline differences in essential metal metabolism in subcategories of patients with disturbance of consciousness (coma/VS vs MCS using CRS-r scale range: 0 to 23).
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)	Baseline differences in essential metal blood concentration in subcategories of patients with acquired brain injury ( etiology: traumatic vs non-traumatic).
Correlation between clinical outcome related to autonomy and disability and essential metal blood concentration	At baseline (T0) and 30 days (T1)	The clinical evaluation will be carried out using the following evaluation scales: Barthel Index (mBI) (range 0 to 100), the Disability Rating Scale (DRS) (range 0 to 29). As regards peripheral venous blood sampling, these will be performed in order to measure the following biological markers on serum: Fe, range men 65 and 178 µg/dL, women 50 and 170 µg/dL; Zn, range 75 -110 µg/dL; Cu, range men 60-160 µg/dL, women: 80-155 µg/dL; Ferr, range men 20-200 ng/mL, women 20-120 ng/mL; Tf, range men: 215-365 mg/dL, women: 250-380 mg/dL; Cp, range 20-50 mg/dL: Non-Cp Cu, range less than 5 µg/dL.
Correlation between clinical outcome related to motor performance and essential metal blood concentration	At baseline (T0) and 30 days (T1)	The clinical evaluation will be carried out using the following evaluation scales: Motricity Index (range 0 to 100 points). As regards peripheral venous blood sampling, these will be performed in order to measure the following biological markers on serum: Fe, range men 65 and 178 µg/dL, women 50 and 170 µg/dL; Zn, range 75 -110 µg/dL; Cu, range men 60-160 µg/dL, women: 80-155 µg/dL; Ferr, range men 20-200 ng/mL, women 20-120 ng/mL; Tf, range men: 215-365 mg/dL, women: 250-380 mg/dL; Cp, range 20-50 mg/dL: Non-Cp Cu, range less than 5 µg/dL.
Correlation between clinical outcome related to state of consciousness and cognitive level and essential metal blood concentration	At baseline (T0) and 30 days (T1)	The clinical evaluation will be carried out using the following evaluation scales: Coma Recovery Scale - Journal (CRS-r) (range 0 to 23), the Level of Cognitive Functioning (LCF) (range10 levels) and the Full Outline of UnResponsiveness (FOUR-Score) (range 0 to 16). As regards peripheral venous blood sampling, these will be performed in order to measure the following biological markers on serum: Fe, range men 65 and 178 µg/dL, women 50 and 170 µg/dL; Zn, range 75 -110 µg/dL; Cu, range men 60-160 µg/dL, women: 80-155 µg/dL; Ferr, range men 20-200 ng/mL, women 20-120 ng/mL; Tf, range men: 215-365 mg/dL, women: 250-380 mg/dL; Cp, range 20-50 mg/dL: Non-Cp Cu, range less than 5 µg/dL.

Trial Locations

Locations (1)

UOC Neuroriabilitazione ad alta intensità , Policlinico "A. Gemelli"; 🇮🇹 Roma, RM, Italy