CITADEL: Effectiveness of CITicoline in Preventing Cognitive Decline After DELirium

NCT07804498 | Recruiting Phase 2 DMC

• 2 other identifiers: 2025-522306-21-002025
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

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.

Conditions

Cognitive Decline; Delirium

Keywords

Cognitive decline; Delirium; Citicoline; Hip fracture

Outcome Measures

Primary Outcomes (1)

• 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

  Montreal Cognitive Assessment (MoCA) performed at discharge and at 6 months post-randomization

  6 months

Secondary Outcomes (3)

• 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

• 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

• Evaluate differences in adverse events between the intervention and control groups during the 6-month follow-up period post-randomization.

  6 months

Study Arms (2)

Experimental: Citicoline Intervention Group

EXPERIMENTAL

Participants randomized to the experimental arm will be administered Citicoline (TRAUSAN) at 1000 mg/day as an oral solution in single-dose 10 mL sachets (100 mg/mL), starting the day after hospital discharge and continued for 6 months (participants will receive a 3-month supply at enrollment and a further 3-month supply at the scheduled 3-month follow-up visit). Study drug accountability will be maintained through tracking of dispensed and returned sachets at follow-up visits. Participants will document daily intake, missed doses, treatment deviations, adverse events, and any changes in concomitant therapies in a diary (with the help of their caregivers), which will be reviewed at follow-up visits.

Drug: Citicoline

No Intervention: Control Group

NO INTERVENTION

The control group will not receive any specific pharmacological treatment for cognitive decline prevention after delirium. Non-pharmacological interventions, such as those suggested by the HELP program to prevent delirium during hospitalization, will be equally provided in both the intervention and control groups as part of the in-hospital usual clinical care in all patients.

Interventions

Citicoline DRUG

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.

Experimental: Citicoline Intervention Group

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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)
• Clinical diagnosis of delirium (arising from any cause), ascertained pre- or post-operatively using the 4AT score (cut-off ≥ 4/12)
• 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
• Prognosis quoad vitam ≥ 3 months
• Availability of a formal or informal caregiver who may help the participant to take the prescribed dose and follow the visit schedule
• 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.

You may not qualify if:

• 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)
• Current therapy with citicoline
• 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
• 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
• Persistent in-hospital delirium (≥ 6 days or still present 24 hours prior to discharge).

Sponsors & Collaborators

• University of Milano Bicocca: lead

Study Sites (1)

IRCCS San Gerardo dei Tintori Foundation

Monza, Monza E Brianza, 20900, Italy

RECRUITING

Related Publications (26)

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MeSH Terms

Conditions

Cognitive Dysfunction; Delirium; Hip Fractures

Interventions

Cytidine Diphosphate Choline

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Femoral Fractures; Fractures, Bone; Wounds and Injuries; Hip Injuries; Leg Injuries

Intervention Hierarchy (Ancestors)

Choline; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Cytidine Diphosphate; Cytosine Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Officials

• Giuseppe Bellelli, Medical doctor, full professor

  University of Milano-Bicocca, IRCCS San Gerardo dei Tintori Foundation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Cristina Ferrara, Medical doctor and PhD

CONTACT

+39 0392339719; mariacristina.ferrara@unimib.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 31, 2026
• First Posted: September 4, 2026
• Study Start: June 3, 2026
• Primary Completion (Estimated): December 5, 2027
• Study Completion (Estimated): December 5, 2027
• Last Updated: September 9, 2026

Record last verified: 2026-09

Locations

IT (1)