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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a non-randomized, Phase 2 clinical trial designed to measure the cerebral blood flow (CBF) response to inhaled nitric oxide in acute ischemic stroke patients and healthy subjects. The monitoring is a 35 minute session during which cerebral hemodynamics will be monitored with both diffuse correlation spectroscopy (DCS) and transcranial doppler ultrasonography (TCD) while blood pressure, heart rate, cardiac output, respiratory rate, end oxygen saturation, and inhaled nitric oxide (NO)/nitrogen dioxide (NO2) concentration, are continuously monitored.

Research Team

Steven R Messe, M.D.

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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