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Detection of Hypoxia in Human Thoracic Aorta Using Pimonidazole Hydrochloride

Primary Purpose

Aortic Aneurysm, Thoracic

Status

Suspended

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Pimonidazole hydrochloride

About this trial

This is an interventional basic science trial for Aortic Aneurysm, Thoracic focused on measuring Thoracic Aortic Aneurysm, Hypoxia, Ascending Aorta, Hypoxyprobe, Pimonidazole

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
Adequate hematologic functions:
- White blood cells > 2500/µ;
- Platelets > 100,000/µL;
- Hemoglobin > 8 g/dl.
Adequate renal functions: serum creatinine < 2.0 mg/dl.
Adequate hepatic function: serum alkaline phosphatase, bilirubin, and serum glutamate oxaloacetate transaminase twice normal levels.
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.
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.
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:

Severe septicemia or severe infection in the 4 weeks prior to study entry;
The subject has a baseline NIHSS > 1 or modified Rankin Scale > 1.
Active participation in other research therapy for cardiovascular repair/regeneration;
Pregnant or breastfeeding at time of screening;
Cardiothoracic surgery within 30 days prior to screening;
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).

Sites / Locations

University of Maryland, Baltimore

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Non aneurysmal

Aneurysmal

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

NCT ID

NCT03410420

First Posted

January 8, 2018

Last Updated

November 19, 2022

Sponsor

University of Maryland, Baltimore

1. Study Identification

Unique Protocol Identification Number

NCT03410420

Brief Title

Detection of Hypoxia in Human Thoracic Aorta Using Pimonidazole Hydrochloride

Official Title

Detection of Hypoxia in Human Thoracic Aorta Using Pimonidazole Hydrochloride

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Suspended

Why Stopped

Study is in the process of changing institutions, and is currently being held until the process of transferring institutions, including all regulatory steps is completed.

Study Start Date

October 1, 2018 (Actual)

Primary Completion Date

February 1, 2025 (Anticipated)

Study Completion Date

February 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Maryland, Baltimore

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Aortic Aneurysm, Thoracic

Keywords

Thoracic Aortic Aneurysm, Hypoxia, Ascending Aorta, Hypoxyprobe, Pimonidazole

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Model Description

This is a prospective study designed to determine the safety and value of pimonidazole hydrochloride to detect levels of tissue hypoxia in patients presenting with ascending aortic aneurysm

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Non aneurysmal

Arm Type

Active Comparator

Arm Description

Arm Title

Aneurysmal

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Pimonidazole hydrochloride

Intervention Description

administration of pimonidazole-HCl

Primary Outcome Measure Information:

Title

Detection of pimonidazole-HCl in aortic specimens

Description

Levels of pimonidazole-HCl will be quantified in aortic specimens from patients who were administered pimonidazole-HCl prior to surgery

Time Frame

< 1 week

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

100 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Adequate hematologic functions: White blood cells > 2500/µ; Platelets > 100,000/µL; Hemoglobin > 8 g/dl. Adequate renal functions: serum creatinine < 2.0 mg/dl. Adequate hepatic function: serum alkaline phosphatase, bilirubin, and serum glutamate oxaloacetate transaminase twice normal levels. 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. 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. 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: Severe septicemia or severe infection in the 4 weeks prior to study entry; The subject has a baseline NIHSS > 1 or modified Rankin Scale > 1. Active participation in other research therapy for cardiovascular repair/regeneration; Pregnant or breastfeeding at time of screening; Cardiothoracic surgery within 30 days prior to screening; 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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thomas G Gleason, MD

Organizational Affiliation

University of Maryland, Baltimore

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Maryland, Baltimore

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Detection of Hypoxia in Human Thoracic Aorta Using Pimonidazole Hydrochloride

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