Maximizing trEatment of Neurological Dysfunction Using INtravenous Guanfacine Study

NCT04742673 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: U115433R01AG053582-05S1
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

This proof-of-concept study examines whether the acute brain dysfunction that occurs in critically ill patients is improved by administration of intravenous guanfacine.

Conditions

Cognitive Impairment; Critical Illness; Delirium

Outcome Measures

Primary Outcomes (1)

• Number of Days Alive Without Delirium or Coma

  14 days after randomization

Secondary Outcomes (5)

• Days Alive and Free of Mechanical Ventilation

  28 days after randomization

• Days Alive and Free of the Intensive Care Unit

  28 days after randomization

• Cognitive Function

  180 days after randomization

• Days Alive and Free of the Hospital

  28 days after randomization

• Mortality

  90 days after randomization

Other Outcomes (9)

• Physical Function

  180 days after after randomization

• Global Health

  180 days after after randomization

• Pain Interference

  180 days after randomization

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants will flow through the trial in the following manner: 1. Consent in ICU: perform required inclusion/exclusion assessments; discuss study goals, activities, and requirements; obtain informed consent 2. Pre-randomization phase: twice daily assessments of mental status 3. Randomize delirious patients: IV guanfacine or placebo 4. Interventional Trial phase: study drug administration, mental status assessments, safety monitoring 5. Blood draws: collect blood samples on Interventional Trial Phase days 1 and 2 6. Follow-up assessments: telephone and online questionnaires at 30, 90, and 180 days after hospital discharge.

Drug: Placebo

IV Guanfacine

EXPERIMENTAL

Participants will flow through the trial in the following manner: 1. Consent in ICU: perform required inclusion/exclusion assessments; discuss study goals, activities, and requirements; obtain informed consent 2. Pre-randomization phase: twice daily assessments of mental status 3. Randomize delirious patients: IV guanfacine or placebo 4. Interventional Trial phase: study drug administration, mental status assessments, safety monitoring 5. Blood draws: collect blood samples on Interventional Trial Phase days 1 and 2 6. Follow-up assessments: telephone and online questionnaires at 30, 90, and 180 days after hospital discharge.

Drug: Guanfacine

Interventions

Guanfacine DRUG

Patients randomized to the IV Guanfacine arm will receive intravenous guanfacine when they exhibit ICU delirium.

IV Guanfacine

Placebo DRUG

Patients randomized to the placebo arm will receive intravenous normal saline when they exhibit ICU delirium.

Placebo

Eligibility Criteria

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

You may qualify if:

• adult patients (≥ 18 years old)
• requiring admission to an ICU
• for treatment of respiratory failure (e.g., mechanical ventilation, non-invasive positive pressure ventilation \[NIPPV\], Extracorporeal Membrane Oxygenation \[ECMO\], optiflow) and/or for treatment of shock (e.g., vasopressors, ECMO, intra-aortic balloon pump \[IABP\]).

You may not qualify if:

• allergic to guanfacine, clonidine, or dexmedetomidine
• on home antipsychotics who, therefore, require continuing antipsychotic administration in the hospital
• co-enrolled in another interventional trial examining similar outcomes or in a study that does not allow co-enrollment
• expected death within 24 hours of enrollment or lack of commitment to aggressive treatment by family or the medical team (e.g., likely withdrawal of life support measures within 24 hours of screening)
• acute or subacute neurologic deficit that is expected to make the patient incapable of living independently after hospital discharge due to cognitive deficits (e.g., stroke, intracranial hemorrhage, cranial trauma, intracranial malignancy, anoxic brain injury, cerebral edema).
• dementia or other chronic neurologic disease or disorder that makes the patient incapable of living independently at baseline
• active substance abuse, psychotic disorder, or homelessness without a secondary contact person (which would make long-term follow-up difficult)
• blindness or deafness (which would prevent assessment of the study's outcomes)
• pregnancy or breastfeeding
• prisoner
• Cardiac surgery within the current hospitalization.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Massachusetts General Hospital: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

Related Publications (1)

• Arnsten AFT, Ishizawa Y, Xie Z. Scientific rationale for the use of alpha2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders. Mol Psychiatry. 2023 Nov;28(11):4540-4552. doi: 10.1038/s41380-023-02057-4. Epub 2023 Apr 7.

  PMID: 37029295 DERIVED

MeSH Terms

Conditions

Critical Illness; Delirium; Cognitive Dysfunction

Interventions

Guanfacine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids

Results Point of Contact

• Title: Christopher Hughes
• Organization: Vanderbilt University Medical Center

christopher.hughes@vumc.org

615-322-5000

Study Officials

• Christopher Hughes, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesiology

Study Record Dates

• First Submitted: January 29, 2021
• First Posted: February 8, 2021
• Study Start: May 4, 2021
• Primary Completion: March 30, 2024
• Study Completion: November 30, 2025
• Last Updated: February 19, 2026
• Results First Posted: May 6, 2025

Record last verified: 2025-05

Locations

US (1)