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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether guanfacine, administered intravenously, can improve brain function in critically ill patients. The focus is on those in the ICU for severe conditions such as breathing problems or shock. Participants will receive either guanfacine or a placebo to determine its effect on mental status. Ideal candidates are those in the ICU requiring intensive breathing support or treatment for shock. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that guanfacine is generally safe for people and is well-tolerated by both very sick patients and children with ADHD. One study found that guanfacine helped reduce confusion and the need for sedative drugs in hospitalized patients. Another review concluded that guanfacine is a safe and well-tolerated medication for individuals with various types of hyperactivity. Overall, the safety data for guanfacine is reassuring, with no major side effects reported in these studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for neurological dysfunction in critical illness focus on managing symptoms with sedatives or antipsychotics. However, Guanfacine offers a fresh approach by acting on alpha-2 adrenergic receptors in the brain, potentially calming hyperactive neurological responses. Researchers are excited because this mechanism could address the root of cognitive disturbances, like delirium, rather than just the symptoms. Additionally, Guanfacine's use in an intravenous form allows for precise dosing in critically ill patients, which could lead to more immediate and controlled effects compared to oral medications. This unique approach may provide quicker, more effective relief for patients experiencing severe neurological dysfunction in the ICU.

What evidence suggests that guanfacine might be an effective treatment for acute brain dysfunction in critically ill patients?

Research has shown that guanfacine might help with sudden brain problems in very sick patients. In this trial, participants will receive either IV guanfacine or a placebo. One study found that guanfacine reduced the severity of confusion (delirium) and decreased the need for calming medications in hospitalized patients. Other studies indicate that guanfacine is safe for both very sick adults and children with ADHD. Overall, these findings suggest that guanfacine could be useful for managing brain issues in critical care settings. ^{1 2 3 4 6}

Who Is on the Research Team?

Christopher G Hughes, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. withpower.com withpower.com/trial/phase-3-delirium-4-2021-5df4e

Guanfacine for Neurological Dysfunction in Critical Illness Guanfacine is generally considered safe for humans, with studies showing it is well-tolerated in both critically ill patients and children with ADHD.

2. sciencedirect.com sciencedirect.com/science/article/pii/S144127722400036X

Efficacy and safety of guanfacine in hospitalized patients ... Guanfacine therapy was associated with delirium attenuation and a reduction in the use of sedative agents. Median dosage was 1.5 mg daily.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9899070/

A Retrospective Analysis of Guanfacine for ... - PubMed Central Based on our retrospective study, guanfacine is a well-tolerated medication for the management of delirium. Even in medically and critically ill ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04742673?tab=results

Study Results | Maximizing trEatment of Neurological ... A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved ...

5. ctv.veeva.com ctv.veeva.com/study/maximizing-treatment-of-neurological-dysfunction-using-intravenous-guanfacine-study

Maximizing trEatment of Neurological Dysfunction Using ... This proof-of-concept study examines whether the acute brain dysfunction that occurs in critically ill patients is improved by administration of ...

6. adhdevidence.org adhdevidence.org/blog/safety-and-efficacy-of-long-term-use-of-guanfacine-for-adults-with-adhd

Safety and efficacy of long-term use of guanfacine for ... A Japanese research team set out to explore the long-term administration of once-daily GXR in adults with ADHD over a year of treatment.