Guanfacine for Neurological Dysfunction in Critical Illness

(MENDING Trial)

Overseen By Christopher Hughes, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Must not be taking: Antipsychotics

Disqualifiers: Heart block, Neurologic deficit, Dementia, Substance abuse, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

46 Participants Needed

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on antipsychotics at home and need to continue them in the hospital, you cannot participate.

What data supports the effectiveness of the drug guanfacine for neurological dysfunction in critical illness?

Research shows that guanfacine can help reduce the need for sedatives and opioids in patients with delirium, a condition involving confusion and agitation, and it has been used successfully to manage anxiety and agitation after surgery. This suggests it might be helpful for neurological issues in critically ill patients. ^{1 2 3 4 5}

Is guanfacine generally safe for humans?

Guanfacine is generally considered safe for humans, with studies showing it is well-tolerated in both critically ill patients and children with ADHD. Common side effects include sleepiness and fatigue, and serious heart-related issues are rare. However, overdose can lead to more severe symptoms like low blood pressure and slow heart rate. ^{1 2 4 5 6}

How does the drug guanfacine differ from other treatments for neurological dysfunction in critical illness?

Guanfacine is unique because it is an oral medication that acts as an alpha-2 adrenergic agonist, which can help manage symptoms like anxiety and agitation in critically ill patients without causing significant cardiovascular side effects. Unlike other sedatives, it may reduce the need for additional sedatives and opioids, allowing patients to better participate in physical therapy and recover more effectively. ^{1 2 3 4 7}

Research Team

Christopher G Hughes, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

Adults over 18 needing ICU care for respiratory failure or shock can join this trial. Excluded are prisoners, those with sensory impairments preventing outcome assessment, expected death within 24 hours, pregnant/breastfeeding women, certain heart conditions, allergies to study drugs, on home antipsychotics or with cognitive deficits making independent living impossible.

Inclusion Criteria

I needed intensive care for severe breathing problems or shock.

Exclusion Criteria

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)

Pregnancy or breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Pre-randomization

Twice daily assessments of mental status before randomization

1 week

Daily assessments (in-person)

Interventional Trial

Study drug administration, mental status assessments, safety monitoring, and blood draws

14 days

Daily visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with telephone and online questionnaires

180 days

3 follow-up assessments (remote)

Treatment Details

Interventions

• Guanfacine
• Placebo

Trial Overview The study is testing if intravenous guanfacine can improve brain dysfunction in critically ill patients. Participants will either receive guanfacine or a placebo to see which is more effective at treating delirium and cognitive impairment during critical illness.

Participant Groups

Group I: IV Guanfacine Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Effect of Enteral Guanfacine on Dexmedetomidine Use in the ICU. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A Retrospective Analysis of Guanfacine for the Pharmacological Management of Delirium. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

The efficacy of guanfacine in reducing perioperative hemodynamic changes and volatile anesthetic requirement. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Enteral Guanfacine to Treat Severe Anxiety and Agitation Complicating Critical Care After Cardiac Surgery. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Guanfacine for attention deficit and hyperactivity disorder in pediatrics: a systematic review and meta-analysis. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Delayed Signs and Symptoms of Extended Release Guanfacine Overdose in Two Adolescent Patients: Implications of Monitoring on the Psychiatry Unit. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Guanfacine's mechanism of action in treating prefrontal cortical disorders: Successful translation across species. [2021]