Clinical trial NCT06911515: Evaluation of Essential Metal Metabolism
Official title: Evaluation of Essential Metal Metabolism in Patients With Disorders of Consciousness
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Disturbance of Consciousness
Alteration of Metabolism
Essential Metals
Keywords: patients with disturbance of consciousness
essential metal
metabolism status
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2025-04-04
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
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

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Blood concetration of essential metal in patients with acquired brain injury
timeFrame: Changes from baseline (T0), after 30 days of treatment (T1)
Secondary outcomes:
measure: Differences in essential metal blood concentration in subcategories of patients with impaired consciousness
timeFrame: At baseline (T0) and 30 days (T1)
measure: Differences in essential metal blood concentration in subcategories of patients with acquired brain injury (traumatic vs non-traumatic)
timeFrame: At baseline (T0) and 30 days (T1)
measure: Correlation between clinical outcome related to autonomy and disability and essential metal blood concentration
timeFrame: At baseline (T0) and 30 days (T1)
measure: Correlation between clinical outcome related to motor performance and essential metal blood concentration
timeFrame: At baseline (T0) and 30 days (T1)
measure: Correlation between clinical outcome related to state of consciousness and cognitive level and essential metal blood concentration
timeFrame: At baseline (T0) and 30 days (T1)
Other outcomes:
Locations:
city: Roma
country: Italy
facility: UOC Neuroriabilitazione ad alta intensità , Policlinico "A. Gemelli"
state: RM
Study officials:
affiliation: Fondazione Policlinico Universitario A. Gemelli, IRCCS
name: Stefano mr Bonomi, MD,
role: STUDY_CHAIR
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