Cognitive Decline, Delirium
Conditions
Keywords
Cognitive decline, Delirium, Citicoline, Hip fracture
Brief summary
The aim of this study is to assess whether citicoline (TRAUSAN), a neuroprotective agent involved in membrane phospholipid synthesis and neurotransmission, can prevent or attenuate cognitive decline in older adults who develop perioperative delirium during hospitalization for proximal hip fracture. Delirium is a frequent and severe complication in this population and is associated with cognitive and functional deterioration, institutionalization, and mortality. Participants will be randomly assigned (1:1) to receive citicoline 1000 mg/day for 6 months after discharge, or usual care. Cognitive and functional status will be evaluated at discharge and subsequently at 3 and 6 months follow-up visits.
Interventions
DRUGCiticoline
Citicoline acts as a neuroprotective agent by supporting membrane integrity, modulating neurotransmission, and reducing oxidative stress and neuronal damage, with potential benefits on cognitive and functional recovery. However, no previous trials has investigated the effect of citicoline in preventing cognitive decline after delirium. Participants in the experimental arm of this study will receive citicoline (TRAUSAN) 1000 mg/day as an oral solution in single-dose 10 mL sachets (100 mg/mL), starting the day after hospital discharge, for a total duration of 6 months. 1 mL of citicoline solution contains 100 mg of citicoline (as sodium salt). Excipient(s) with known effects: 1 mL of Citicoline oral solution contains 200 mg of liquid sorbitol, 10 mg of glycerin, 1.8 mg of methyl parahydroxybenzoate, 0.42 mg of propyl parahydroxybenzoate, 1.4 mg of potassium sorbate, 0.012 mg of Ponceau 4R red, and other excipients.
Sponsors
University of Milano Bicocca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Intervention model description
The study is a phase II, open-label, randomized trial assessing citicoline's effect on cognitive decline after delirium in older adults with hip fractures. Patients with delirium are enrolled after screening for inclusion-exclusion criteria, and then randomized 1:1 to receive citicoline or usual care.
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Individuals aged ≥65 who were admitted for a proximal hip fracture to the Orthogeriatric Unit and underwent hip fracture surgery (IRCCS San Gerardo dei Tintori Foundation, Monza) 2. Clinical diagnosis of delirium (arising from any cause), ascertained pre- or post-operatively using the 4AT score (cut-off ≥ 4/12) 3. Diagnosis of chronic vascular encephalopathy (corroborated by clinical documentation or previous cerebral imaging), i.e. evidence of neurological and cognitive disorder resulting from cerebrovascular accidents 4. Prognosis quoad vitam ≥ 3 months 5. Availability of a formal or informal caregiver who may help the participant to take the prescribed dose and follow the visit schedule 6. Informed consent, freely granted from the participant or from his/her legal guardian (or from an impartial witness in cases where the patient is unable to sign but clearly expresses the will to participate), and acquired before the randomization.
Exclusion criteria
1. Diagnosis of severe dementia (defined by medical clinical records or by the presence of an AD8 score ≥6 and a Global Deterioration Scale score ≥6) 2. Current therapy with citicoline 3. Any contraindications to citicoline (TRAUSAN), including allergy to acetylsalicylic acid or excipients contained in the drug, previous adverse reactions to citicoline, hypertonia of the parasympathetic nervous system, low-sodium diet 4. Clinical conditions or situations other than the condition being studied, which in the opinion of the researchers could interfere with the study or not allow optimal participation 5. Persistent in-hospital delirium (≥ 6 days or still present 24 hours prior to discharge).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess potential differences in cognitive profiles 6 months post-randomization among older adults hospitalized for proximal hip fractures with perioperative delirium, comparing the intervention arm (citicoline,TRAUSAN) to the control arm | 6 months | Montreal Cognitive Assessment (MoCA) performed at discharge and at 6 months post-randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate differences in cognitive profiles in older adults hospitalized for proximal hip fractures at 0 (discharge), 3, and 6 months after randomization, comparing the intervention (citicoline, TRAUSAN) to the control arm. | Discharge, 3 months, and 6 months | Montreal Cognitive Assessment (MoCA) performed at discharge and at 3 and 6 months post-randomization |
| Evaluate differences in functional profiles from 3 to 6 months post-randomization between the intervention (citicoline, TRAUSAN) and control arm. | 3 months and 6 months | Short Physical Performance Battery (SPPB), performed at 3 and 6 months post-randomization |
| Evaluate differences in adverse events between the intervention and control groups during the 6-month follow-up period post-randomization. | 6 months | Rates of adverse events (quantity/seriousness) during the 6-months follow-up after randomization |
Countries
Italy
Contacts
CONTACTMaria Cristina Ferrara, Medical doctor and PhD
PRINCIPAL_INVESTIGATORGiuseppe Bellelli, Medical doctor, full professor
University of Milano-Bicocca, IRCCS San Gerardo dei Tintori Foundation
Outcome results
None listed