Detection of Hypoxia in Human Thoracic Aorta Using Pimonidazole Hydrochloride

This is a prospective study designed to determine the safety and value of Hypoxyprobe-1 (pimonidazole hydrochloride (-HCl)) to detect levels of tissue hypoxia in patients presenting with ascending aortic aneurysm.

Study Overview

• Status: Suspended
• Conditions: Aortic Aneurysm, Thoracic
• Intervention / Treatment: Drug: Pimonidazole hydrochloride

Detailed Description

The proposed study is designed to identify the level of tissue hypoxia in patients presenting with ascending aortic aneurysm. Ascending aortic aneurysms affect approximately 15,000 people in the United States each year, and represent a serious clinical problem because there is a known, but unspecified risk of aortic rupture or dissection. Despite progress made in the surgical management of ascending aortic aneurysms, the molecular and cellular mechanisms involved remain elusive. However, indirect evidence of tissue hypoxia have recently been described in the literature.

This pilot study will use pimonidazole-HCl, a compound that is retained by hypoxic cells and that has been used for detection of tissue hypoxia in human since the early 2000s. This pilot study will involve twenty patients who are candidates for aortic replacement due to aneurysm and twenty non-aneurysmal patients undergoing coronary artery bypass graft (controls). Patients will be administered pimonidazole-HCl orally in a single dose (0.5g/m2) 24 hours prior to scheduled surgical time. During surgery, the resected aneurysmal aortic specimens (for patients undergoing aortic replacement) or aortic punch (for patients undergoing coronary artery bypass graft) will be harvested. Tissue hypoxia will be qualitatively and quantitatively assessed in the investigator's research laboratory. Based on previous toxicological animal studies and previous use in human studies, the anticipated risk of severe or serious side effect will be relatively minimal.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Baltimore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adults ≥ 18 years of age who require one of the following open surgery:

   • Ascending thoracic aorta repair due to aneurysm;
   • Aortic valve replacement due to aortic valve insufficiency;
   • Coronary artery bypass graft procedure due to coronary heart disease. Imaging CT scans and echography defining the presence of ascending aortic aneurysm will be centrally reviewed prospectively to ensure adherence to subject inclusion criteria.

2. Adequate hematologic functions:

   • White blood cells > 2500/µ;
   • Platelets > 100,000/µL;
   • Hemoglobin > 8 g/dl.
3. Adequate renal functions: serum creatinine < 2.0 mg/dl.
4. Adequate hepatic function: serum alkaline phosphatase, bilirubin, and serum glutamate oxaloacetate transaminase twice normal levels.
5. If the subject or partner is of childbearing potential, he or she must be willing to use adequate contraception (hormonal or barrier method or abstinence) from the time of screening and for a period of at least 16 weeks after procedure.
6. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form, release of medical information, and Health Insurance Portability and Accountability Act (HIPAA) documentation.
7. Female subjects of childbearing potential must have a negative serum pregnancy test at screening. human chorionic gonadotropin levels will be assessed for all women of childbearing years prior to the procedure.

Exclusion Criteria:

1. Severe septicemia or severe infection in the 4 weeks prior to study entry;
2. The subject has a baseline NIHSS > 1 or modified Rankin Scale > 1.
3. Active participation in other research therapy for cardiovascular repair/regeneration;
4. Pregnant or breastfeeding at time of screening;
5. Cardiothoracic surgery within 30 days prior to screening;
6. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Non aneurysmal; Intervention: four non-aneurysmal patients undergoing coronary artery bypass graft or aortic valve replacement will be administered pimonidazole-HCl orally in a single dose (0.5g/m2) 24 hours prior to scheduled surgical time.	Drug: Pimonidazole hydrochloride; administration of pimonidazole-HCl
Experimental: Aneurysmal; Intervention: four patients who are candidates for aortic replacement due to aneurysm will be administered pimonidazole-HCl orally in a single dose (0.5g/m2) 24 hours prior to scheduled surgical time.	Drug: Pimonidazole hydrochloride; administration of pimonidazole-HCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of pimonidazole-HCl in aortic specimens	Levels of pimonidazole-HCl will be quantified in aortic specimens from patients who were administered pimonidazole-HCl prior to surgery	< 1 week

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Thomas G Gleason, MD, University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Anticipated): February 1, 2025
• Study Completion (Anticipated): February 1, 2025

Study Registration Dates

• First Submitted: January 8, 2018
• First Submitted That Met QC Criteria: January 24, 2018
• First Posted (Actual): January 25, 2018

Study Record Updates

• Last Update Posted (Actual): November 22, 2022
• Last Update Submitted That Met QC Criteria: November 19, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Hypoxia; Hypoxyprobe; Thoracic Aortic Aneurysm; Ascending Aorta; Pimonidazole
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Signs and Symptoms, Respiratory; Aortic Diseases; Aneurysm; Hypoxia; Aortic Aneurysm; Aortic Aneurysm, Thoracic
• Other Study ID Numbers: PRO16050046

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No