Inhaled Nitric Oxide for Stroke

(DOMINO Trial)

Overseen By Devin M Keating

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Steven Messe

Must not be taking: NO donors

Disqualifiers: Stroke, Neurological disease, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how inhaled nitric oxide affects blood flow in the brain for individuals who recently experienced an ischemic stroke and those without neurological issues. The study aims to determine if this treatment can enhance brain circulation, potentially aiding stroke recovery. Participants will inhale nitric oxide for short periods while researchers closely monitor their brain and body responses. Suitable candidates include those who have had an acute ischemic stroke within the last 72 hours or healthy individuals without neurological diseases. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

You cannot participate if you are currently using any NO donor medications like sodium nitroprusside or nitroglycerin. The trial does not specify if you need to stop other medications, so it's best to discuss this with the trial team.

Is there any evidence suggesting that inhaled nitric oxide is likely to be safe for humans?

Research has shown that inhaled nitric oxide (iNO) holds potential benefits for treating stroke patients. Animal studies, including those with mice and rats, demonstrated that it can reduce brain damage and improve recovery after a stroke or heart event.

Regarding safety, research on humans suggests that iNO is generally well-tolerated. Although specific human trials for stroke are ongoing, inhaled nitric oxide is already used in other medical situations, such as treating newborns with certain lung issues, supporting its safety.

Researchers closely monitor participants for side effects, such as changes in blood pressure and heart rate, which are generally manageable. Since this trial is in an early stage, it aims to further evaluate how well people tolerate iNO, an important step before larger studies.

Overall, while more research is needed, current evidence suggests that inhaled nitric oxide is a promising and relatively safe treatment option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for stroke?

Researchers are excited about inhaled nitric oxide (iNO) for stroke because it offers a novel approach to improving cerebral blood flow. Unlike standard treatments like clot-busting drugs or mechanical thrombectomy, which aim to restore blood flow by physically removing or dissolving clots, iNO works by dilating blood vessels, potentially enhancing blood flow to the brain without invasive procedures. This method could offer a quicker, non-invasive alternative to help manage stroke symptoms and improve outcomes.

What evidence suggests that inhaled nitric oxide might be an effective treatment for stroke?

This trial will evaluate the effects of inhaled nitric oxide on stroke patients. Studies have shown that inhaled nitric oxide might help treat sudden strokes by improving blood flow in the brain. It reduced brain injury in animal studies, such as those with mice and rats. Research indicates that inhaled nitric oxide can reduce swelling in the brain after a stroke. Less swelling is crucial because it can help protect the brain from further damage. These findings suggest that inhaled nitric oxide could be a promising treatment for stroke patients by supporting brain health and recovery. ^{1 2 3 4 5}

Who Is on the Research Team?

Steven R Messe, M.D.

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had a stroke in certain areas of the brain and can start the study within 72 hours of their stroke symptoms starting. They must be able to understand and agree to participate by signing an informed consent.

Inclusion Criteria

Stroke Patients: Ability and willingness to sign informed consent

I had a stroke and can start the study within 3 days of my first symptoms.

I had a stroke affecting the front, middle, or back part of my brain.

Exclusion Criteria

I am currently taking medication that releases nitric oxide for my stroke.

I am under 18 and have had a stroke.

I have a history of psychiatric illness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Monitoring

Participants undergo a 35-minute session to measure cerebral blood flow response to inhaled nitric oxide

35 minutes

1 visit (in-person)

Follow-up

Participants are monitored for tolerability issues or adverse events 24 hours after the monitoring session

24 hours

1 follow-up call

What Are the Treatments Tested in This Trial?

Interventions

• Nitric Oxide

Trial Overview The trial tests how breathing in nitric oxide affects blood flow in the brain after a stroke, using special monitoring techniques like DCS and TCD during a single 35-minute session.

How Is the Trial Designed?

Group I: Healthy Controls Experimental Treatment 1 Intervention

The protocol will be a 35-minute monitoring session, during which cerebral hemodynamics will be monitored with both DCS and TCD, while blood pressure, heart rate, cardiac output, respiratory rate, end oxygen saturation, and inhaled nitric oxide concentration, are continuously monitored. 5 minutes of baseline hemodynamics will be assessed, after which the subject will breath iNO for 5 minutes, followed by 5 minutes of room air. This iNO/room air cycle will be repeated with a total of 3 different iNO concentrations. The full protocol will require 35 minutes. Subjects will be called at 24 hours after the monitoring session to determine any tolerability issues or adverse events.

Group II: Acute Ischemic Stroke Experimental Treatment 1 Intervention

Patients will be enrolled in the study within 72 hours of stroke symptom onset. The protocol will be a 35-minute monitoring session, during which cerebral hemodynamics will be monitored with both DCS and TCD, while blood pressure, heart rate, cardiac output, respiratory rate, end oxygen saturation, and inhaled nitric oxide concentration, are continuously monitored. 5 minutes of baseline hemodynamics will be assessed, after which the subject will breath iNO for 5 minutes, followed by 5 minutes of room air. This iNO/room air cycle will be repeated with a total of 3 different iNO concentrations. The full protocol will require 35 minutes. Subjects will be undergo a final assessment at 24 hours after the monitoring session to determine any tolerability issues or adverse events.

Nitric Oxide is already approved in United States for the following indications:

Approved in United States as Inomax for:

• Hypoxic respiratory failure in term and near-term neonates with pulmonary hypertension

Approved in United States as Noxivent for:

• Hypoxic respiratory failure in term and near-term neonates with pulmonary hypertension

Approved in United States as GeNOsyl for:

• Hypoxic respiratory failure in term and near-term neonates with pulmonary hypertension

Who Is Running the Clinical Trial?

Steven Messe

Lead Sponsor

Trials

1

Recruited

40+

Mallinckrodt

Industry Sponsor

Trials

202

Recruited

15,700+

Mario Saltarelli

Mallinckrodt

Chief Medical Officer

MD

Siggi Olafsson

Mallinckrodt

Chief Executive Officer

PhD in Pharmacy

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05871606?term=AREA%5BConditionSearch%5D(%22Ischemia%22)%20AND%20AREA%5BInterventionSearch%5D(%22Nitrous%20oxide%22)&rank=2

Study Details | Inhaled Nitric Oxide in Acute Ischemic Stroke ... Types of outcome measures include primary outcome measure and secondary outcome measure. ... A type of intervention model describing a clinical trial in which two ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10725028/

Inhaled nitric oxide suppresses neuroinflammation in ... In the current study, we investigated whether alleviating vascular dysfunction by restoring vascular nitric oxide (NO) reduces post-stroke inflammation.

3. withpower.com withpower.com/trial/phase-1-ischemic-stroke-5-2023-7e3c0

Inhaled Nitric Oxide for Ischemic Stroke (iNO Trial) It has been effective in reducing brain injury in mice and improving outcomes after cardiac arrest in rats, suggesting potential benefits for ischemic stroke.

4. jneuroinflammation.biomedcentral.com jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-023-02988-3

Inhaled nitric oxide suppresses neuroinflammation in ... In the current study, we investigated whether alleviating vascular dysfunction by restoring vascular nitric oxide (NO) reduces post-stroke inflammation.

5. ahajournals.org ahajournals.org/doi/10.1161/circresaha.111.253419

Inhalation of Nitric Oxide Prevents Ischemic Brain Damage ... Inhaled nitric oxide thus may provide a completely novel strategy to improve penumbral blood flow and neuronal survival in stroke or other ischemic conditions.