Vasodilator Therapy With Isosorbide Mononitrate or Diltiazem to Reduce Vasotoxicity in Patients With Gastrointestinal Cancer Receiving Fluoropyrimidine Therapy

May 29, 2026 updated by: Mayo Clinic

Vasotoxicity Surveillance Using EndoPAT: The VASA Pilot Study

This phase I/II trial compares the effect of drugs that causes widening of blood vessels as a result of smooth muscle relaxation (vasodilator therapy) with isosorbide mononitrate, diltiazem or placebo to reduce vasotoxicity in patients with gastrointestinal cancer receiving fluoropyrimidine therapy. Some patients develop chest pain (possibly even a heart attack, a drop in heart function, or a rhythm abnormality) during treatment with a class of cancer drugs known as fluoropyrimidines, which include 5-Fluorouracil (5-FU) and capecitabine. These side effects are believed to be due to the development of an abnormal reactivity of the blood vessels referred to as vasospasm. Vasotoxicity is damage or toxicity inflicted upon blood vessels (vascular system), often causing dysfunction, remodeling, or narrowing (vasoconstriction). It is a broad term used to describe the detrimental effects of certain agents, such as chemotherapy drugs. Researchers want to evaluate how often the reactivity of blood vessels becomes abnormal, during the treatment with 5-FU or capecitabine and how clinically relevant and controllable/preventable this phenomenon is in patients with gastrointestinal cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Interventional & Ischemic Heart Disease Research Team
  • Phone Number: 507-255-1724

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Principal Investigator:
          • Joerg Herrmann, MD
        • Contact:
        • Contact:
          • Interventional & Ischemic Heart Disease Research Team
          • Phone Number: 507-255-1724

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • REGISTRATION: Age ≥ 18 years
  • REGISTRATION: Histologically or cytologically confirmed gastrointestinal malignancy (colon, rectal, gastric, esophageal, or other GI cancer) for which fluoropyrimidine therapy (5-FU or capecitabine) is indicated, either as single agent or in combination with other systemic therapy
  • REGISTRATION: Planned initiation of 5-FU (infusional) or oral capecitabine therapy, either as standard chemotherapy or as a radiosensitizer
  • REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • REGISTRATION: Ability to return to Mayo Clinic for baseline and follow-up EndoPAT testing, electrocardiogram (ECG), Holter monitoring, and blood draws
  • REGISTRATION: Provide written informed consent
  • REGISTRATION: Adequate baseline hemodynamic status: systolic blood pressure ≥ 120 mmHg and resting heart rate ≥ 70 beats/minute (to ensure safety for potential vasodilator therapy in Phase II)
  • RANDOMIZATION: Completed all phase I baseline and follow-up assessments, including EndoPAT, ECG, high-sensitivity cardiac troponin T (hs-TnT), and Holter monitoring
  • RANDOMIZATION: Demonstrated a ≥ 20% decline in reactive hyperemia index (RHI) from baseline at either phase I follow-up assessment as measured by EndoPAT
  • RANDOMIZATION: Adequate hemodynamic status prior to randomization: systolic blood pressure ≥ 120 mmHg and resting heart rate ≥ 70 beats/minute
  • RANDOMIZATION: Ability to tolerate and comply with study medication (isosorbide mononitrate, diltiazem, or placebo) per investigator assessment
  • RANDOMIZATION: Willingness to initiate study medication 5 days before and continue through the assigned fluoropyrimidine treatment cycle
  • RANDOMIZATION: Provide written informed consent for randomization phase

Exclusion Criteria:

  • REGISTRATION: Current or planned treatment with long-acting nitrates or calcium channel blockers at the time of fluoropyrimidine initiation
  • REGISTRATION: Known hypersensitivity or contraindication to nitrates or calcium channel blockers
  • REGISTRATION: Baseline systolic blood pressure < 120 mmHg or resting heart rate < 70 beats/minute
  • REGISTRATION: History of myocardial infarction ≤ 6 months prior to registration, or symptomatic heart failure [decompensated or New York Heart Association (NYHA) III-IV] requiring ongoing therapy
  • REGISTRATION: Recent acute coronary syndrome or coronary revascularization within 3 months of enrollment
  • REGISTRATION: High-grade atrioventricular (AV) block without pacemaker
  • REGISTRATION: Use of PDE-5 inhibitors [e.g. sildenafil (Viagra)] within 48 hours of enrollment
  • REGISTRATION: Uncontrolled intercurrent illness including but not limited to: unstable angina, symptomatic arrhythmias, uncontrolled infection, or psychiatric/social conditions limiting compliance with study requirements
  • REGISTRATION: Physical inability to undergo EndoPAT testing (e.g., digital amputation, severe hand deformity, or other limiting condition)
  • REGISTRATION: Pregnant or nursing persons
  • REGISTRATION: Concurrent enrollment in another interventional clinical trial that, in the opinion of the investigator, would interfere with study endpoints

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Phase I (EndoPAT, ECG, Holter monitoring, blood sample)
Patients undergo EndoPat, ECG, Holter monitoring for 48 hours, and blood sample collection during their SOC 5-FU infusion (any time from 2 hours after start to end of infusion) and 12-36 hours post-infusion or SOC capecitabine infusion 5-8 days after starting cycle 1 and 5-8 days after completing cycle 1, before beginning the next cycle of treatment.
Other: Questionnaire Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Fluorouracil
Given IV
Other Names:
  • 5-Fluracil
  • Fluracil
  • 5 Fluorouracil
  • 5 Fluorouracilum
  • 5 FU
  • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
  • 5-Fluorouracil
  • 5-Fu
  • 5FU
  • AccuSite
  • Carac
  • Fluoro Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757
Procedure: Electrocardiogram
Undergo ECG
Other Names:
  • Electrocardiograms
  • ECG
  • EKG
Drug: Capecitabine
Given IPO
Other Names:
  • Xeloda
  • Ro 09-1978/000
Device: Holter Monitoring
Undergo Holter monitoring
Other Names:
  • Holter Monitor
  • HOLTER CONTINUOUS ECG RECORDING
  • Holter Electrocardiography
Other: Medical Device Usage and Evaluation
Use EndoPAT
Experimental: Phase II arm I (Isosorbide mononitrate)
Patients receive isosorbide mononitrate PO QD for 7-12 days on study. Patients also undergo EndoPat, ECG, Holter monitoring for 48 hours, and blood sample collection on study.
Other: Questionnaire Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Electrocardiogram
Undergo ECG
Other Names:
  • Electrocardiograms
  • ECG
  • EKG
Device: Holter Monitoring
Undergo Holter monitoring
Other Names:
  • Holter Monitor
  • HOLTER CONTINUOUS ECG RECORDING
  • Holter Electrocardiography
Other: Medical Device Usage and Evaluation
Use EndoPAT
Drug: Isosorbide Mononitrate
Given PO
Other Names:
  • Imdur
  • ISMO
  • Monoket
  • Monosordil
Experimental: Phase II arm II (Diltiazem hydrochloride)
Patients receive diltiazem PO QD for 7-12 days on study. Patients also undergo EndoPat, ECG, Holter monitoring for 48 hours, and blood sample collection on study.
Other: Questionnaire Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Electrocardiogram
Undergo ECG
Other Names:
  • Electrocardiograms
  • ECG
  • EKG
Device: Holter Monitoring
Undergo Holter monitoring
Other Names:
  • Holter Monitor
  • HOLTER CONTINUOUS ECG RECORDING
  • Holter Electrocardiography
Other: Medical Device Usage and Evaluation
Use EndoPAT
Drug: Diltiazem Hydrochloride
Given PO
Other Names:
  • Cardizem
  • Diltiazem HCl
Placebo Comparator: Phase II arm III (Placebo administration)
Patients receive placebo PO QD for 7-12 days on study. Patients also undergo EndoPat, ECG, Holter monitoring for 48 hours, and blood sample collection on study.
Other: Questionnaire Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Placebo Administration
Given PO
Procedure: Electrocardiogram
Undergo ECG
Other Names:
  • Electrocardiograms
  • ECG
  • EKG
Device: Holter Monitoring
Undergo Holter monitoring
Other Names:
  • Holter Monitor
  • HOLTER CONTINUOUS ECG RECORDING
  • Holter Electrocardiography
Other: Medical Device Usage and Evaluation
Use EndoPAT

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in reactive hyperemia index (RHI)
Time Frame: Baseline (up to 3 days before start of infusion); during infusion; 12-36 hours post-infusion
Will be analyzed as a continuous variable and paired t-test or Wilcoxon signed-rank test will be used depending on parametric or non-parametric distribution of RHI values. Statistical significance is set at a p-value < 0.05.
Baseline (up to 3 days before start of infusion); during infusion; 12-36 hours post-infusion

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of patients with RHI decline ≥ 20%
Time Frame: Up to 1 year
Assessed from baseline (prechemotherapy) to follow-up assessments during and after fluoropyrimidine exposure. Will be analyzed as a continuous variable and paired t-test or Wilcoxon signed-rank test will be used depending on parametric or non-parametric distribution of RHI values. Statistical significance is set at a p-value < 0.05.
Up to 1 year
Proportion of patients with absolute RHI ≤ 2.0
Time Frame: Up to 1 year
Assessed from baseline (prechemotherapy) to follow-up assessments during and after fluoropyrimidine exposure. Will be analyzed as a continuous variable and paired t-test or Wilcoxon signed-rank test will be used depending on parametric or non-parametric distribution of RHI values. Statistical significance is set at a p-value < 0.05.
Up to 1 year
High-sensitivity troponin T (hsTnT) (indicator of myocardial ischemia)
Time Frame: Up to 1 year
Will be compared between patients with and without a decline in RHI ≥20% from baseline.
Up to 1 year
Presence of Holter abnormalities (ST-segment changes, arrhythmias)
Time Frame: Up to 1 year
Assessed using 48-hour continuous Holter monitoring. Will be compared between patients with and without a decline in RHI ≥20% from baseline.
Up to 1 year
Presence of ischemic symptoms (angina or angina equivalents, dyspnea, claudication)
Time Frame: Up to 1 year
Will be compared between patients with and without a decline in RHI ≥20% from baseline.
Up to 1 year
Seattle Angina Questionnaire (SAQ)
Time Frame: Baseline (up to 3 days before start of infusion); during infusion; 12-36 hours post-infusion
The Seattle Angina Questionnaire (SAQ) is a 19-item questionnaire used to assess self-reported health status and quality of life over the past 4 weeks in patients with coronary artery disease (CAD). Nine questions are answered on a 6-point scale (severely limited, moderately limited, somewhat limited, a little limited, not limited, limited, or did not do for other reasons). The remaining questions are answered using similar scales (e.g., not satisfied at all, mostly dissatisfied, somewhat satisfied, mostly satisfied, highly satisfied). Scores range from 0-100 with higher scores indicating better overall health (fewer symptoms).
Baseline (up to 3 days before start of infusion); during infusion; 12-36 hours post-infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mayo Clinic

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Joerg Herrmann, MD, Mayo Clinic in Rochester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 30, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 2, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 2, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 9, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 2, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 29, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MC250411 (Other Identifier: Mayo Clinic)
  • NCI-2026-01065 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • 25-011528 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings